Clinical and Basic Science Research Programs

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Clinical Research Programs:

Acute Respiratory Distress Syndrome (ARDS)
Gordon Bernard, M.D.
Arthur Wheeler, M.D.
Wes Ely, M.D.
Todd Rice, M.D., M.Sc

Asthma, Sinus, and Allergy Clinical Trial Studies
John Fahrenholz, M.D.
S. Bobo Tanner, M.D.
Ryszard Dworski, M.D.

Asthma Studies
Ryszard Dworski M.D., Ph.D.
Tina Hartert, M.D., M.P.H.
James Sheller, M.D.

Chronic obstructive pulmonary disease (COPD)
Richard Light M.D.

Cystic Fibrosis
Bonnie Slovis, M.D.
Lisa Lancaster, M.D.

Familial Idiopathic Pulmonary Fibrosis (FIPF)
James Loyd, M.D.
William Lawson, M.D.

Familial Primary Pulmonary Hypertension Study
James Loyd, M.D.
John Newman, M.D.

ICU Delirium and Cognitive Impairment
Wes Ely, M.D.
Tim Girard, M.D.

Idiopathic Pulmonary Fibrosis (IPF) Clinical Trials
Lisa Lancaster, M.D.
Jim Loyd, M.D.
Bonnie Slovis, M.D.

Lung Transplant Clinical Trials
James Loyd, M.D.
Ivan Robbins, M.D.
Mark Steele, M.D.

Pleural Diseases
Richard Light, M.D.

Pulmonary Arterial Hypertension Clinical Trials (PPH)
Ivan Robbins, M.D.

 

Severe Sepsis Trials
Gordon Bernard, M.D.
Wes Ely, M.D.
Arthur Wheeler, M.D.
Todd Rice, M.D., M.Sc

Vanderbilt Clinical Trials Coordinating Center
Gordon Bernard, M.D.
Wes Ely, M.D.
Arthur Wheeler, M.D.
Todd Rice, M.D., M.Sc

 


Basic Science Research Programs

Asthma
Stokes Peebles, M.D.
James Sheller, M.D.

ARDS, Lung Inflammation and Host Defense
Timothy Blackwell, M.D.
Brian Christman, M.D.
Lorraine Ware, M.D.
Julie Bastarache, M.D.

Lung Cancer
Pierre Massion, M.D.
Timothy Blackwell, M.D.
Alison Miller, M.D.
Jamshedur Rahman, PhD
Vasiliy Polosukhin, MD, PhD

Molecular Biology Core Lab

Pleural Diseases
Richard Light, M.D.

 

Pulmonary Fibrosis
Timothy Blackwell, M.D.
William Lawson, M.D.
James Loyd, M.D.

Program Projects

Liver-Lung Interactions In The Pathogenesis of Lung Inflammation
Brian Christman, M.D.
James Sheller, M.D.

Pulmonary Hypertension
James West, Ph.D.


Clinical Research Programs

Acute Respiratory Distress Syndrome (ARDS)

ARDS affects approximately 150,000 Americans annually with a mortality rate near 40%. Vanderbilt has long been a center for research into mechanisms and potential treatments for ARDS. This long standing interest has been recognized by governmental and private funding agencies. As a result, the Center for Lung Research within the Division has conducted several hundred individual studies in ARDS and Acute Lung Injury (ALI).

Currently, the National Institutes of Health have funded a multi-year, 11 clinical center project to test treatments for Acute Respiratory Distress Syndrome (ARDS) and Acute Lung Injury (ALI). This group, the NIH/NHLBI ARDS network, is actively pursuing potentially lifesaving clinical treatments for ARDS. Vanderbilt University is one of the clinical centers chosen to participate in this prestigious group. The Vanderbilt center is headed by Dr. Art Wheeler and has completed seven large clinical trials and has three others underway.  Dr. Todd Rice is a Vanderbilt site investigator, and with Dr. Wheeler co-chair of a large multi-center study of enteral nutrition in patients with ALI and ARDS.  Dr. Gordon Bernard is Chairman of the ARDS Network Steering Committee.

Completed ARDS Network projects include:

  1. 1. Ketoconazole as an anti-inflammatory agent in early established ALI and ARDS-completed. This project focused on ketoconazole properties as a thromboxane inhibitor and anti-inflammatory agent. This study found Ketoconazole was not an effective therapy for early ALI/ARDS.
  2. 2. 6 ml/kg versus 12 ml/kg tidal volumes in ALI and ARDS. The "high versus low stretch" hypothesis has long been debated in ALI was tested in the largest study of ALI and ARDS to date. The study proved that mortality can be reduced by up to 22% using a low tidal volume approach.
  3. 3. A study of higher PEEP versus that used in the 6 vs. 12 ml/kg tidal volume study was completed. Among more than 500 patients studied; no significant outcome benefit of higher PEEP could be found despite physiological improvements.
  4. 4. Lisophylline, an anti-inflammatory agent which inhibits lipid peroxidation and cellular injury was tested in a double blind large scale randomized trial but failed to reduce important clinical endpoints such as mortality.
  5. 5. Late rescue corticosteroids. The ARDS network is tested, in a blinded randomized study, the use of methylprednisilone in patients with ARDS persisting for 7 to 28 days. The use of steroids improved some physiological endpoints and hastened temporary liberation from the ventilator but did not change long-term survival. Use of corticosteroids in ALI and ARDS remains quite controversial with insufficient data to suggest routine use.
  6. 6. A randomized trial of pulmonary artery versus central venous catheter monitoring in guiding fluid therapy patients with ALI. A national trial of over 1000 patients showed more complications and no outcome benefit resulting from use of a pulmonary artery catheter.
  7. 7. A study of a more conservative approach to fluid management than that traditionally used in ALI has shown faster removal from the mechanical ventilator with a nominal benefit in mortality.
  8. 8. Albuterol in Treatment of ARDS: A study of frequent scheduled aerosolized beta adrenergic agonist in an attempt to decrease lung water content and inflammation did not alter time on ventilator or survival.
  9. 9. Omega-3 fatty acid and antioxidants as treatment for ARDS:  A study of high fat omega 3 and antioxidant supplements to tube feeding compared to a mostly carbohydrate control.  In contrast to prior smaller studies no survival benefit of omega-3 and antioxidant supplementation could be found.

Ongoing ARDS Network projects include:

      1.  Early versus delayed enteral nutrition in ALI (EDEN trial): A trial examining the value and risks of early full feeding versus delayed full feeding.

      2. Statins in acute lung injury and  ARDS:  This randomized double blind placebo controlled trial is testing the hypothesis that rosuvustatin, can modify inflammation in ALLI and improve patient outcomes compared to placebo.Study coordinators for these studies are:

  • Susan Mogan, RN
  • Margret Hayes, RN

To learn more about the ARDS network, or to discuss possible patients participation in these studies contact Dr. Art Wheeler, Dr. Todd Rice, Dr. Gordon Bernard or one of the ARDS network study coordinators at (615) 322-3412. Personnel are available 24 hours a day.

Asthma, Sinus, and Allergy Clinical Trial Studies

PI: Ryszard Dworski, M.D., Ph.D.

 Amgen

Protocol Number: 20120141; AMG827/Brodalumab

 Title: A randomized, double-blind, placebo controlled study to evaluate the safety and efficacy of Brodalumab in subjects with inadequately controlled asthma and high bronchodilator reversibility. 

Primary Objectives: The primary objective is to evaluate the efficacy of Brodalumab compared with placebo as measured by the change in asthma control (based on the Asthma Control Questionnaire) from baseline at week 24 in subjects with inadequately controlled asthma and high reversibility despite standard of care.

Secondary Objectives: To evaluate the effect of brodalumab compared to placebo at week 24 on:

Asthma exacerbations (event rate defined as the number of events per subject year);

ACQ in inhaled corticosteroid (ICS) +long acting beta-agonist (LABA) strata;

 Asthma exacerbations (event rate) in ICS+LABA strata.

To evaluate the effect of brodalumab compared to placebo at week 24 on:

Daily asthma symptoms as measured by the asthma symptom diary;

Lung function based on pre-bronchodilator forced expirator volume in one second rescue short-acting beta-agonist (SABA) use;

Time to first exacerbation;

Asthma exacerbations (subject incidence as defined by percentage of subjects with > 1 exacerbation

Asthma Quality of Life Questionnaire (AQLQ) score;

AM and PM Peak expiratory flow rate (PEFR);

AM and PM variation in PEFR;

Asthma symptom-free days as measured by the asthma symptom diary;

To evaluate the safety of brodalumab;

To evaluate the pharmacokinetics (PK) of brodalumab in subjects with asthma.

Study Design: After completing all screening assessments and meeting all eligibility criteria, subjects will undergo 3 run-in visits over 4 weeks.   Following the run-in visits, eligibility of ACQ, FEV and reversibility will be confirmed at baseline.  If eligible, subjects will be randomized in a 1:1 ration to receive brodalumab 210 mg or placebo every 2 weeks respectively.  Randomization will be stratified based on the current use of LABAs and number of prior exacerbations in the past year before screening.  Enrollment into the strata without current use of a LABA will be limited to approximately 96 subjects.   After the initial dose of investigational product is administered, subjects will be followed for up to 24 weeks in the double-blind placebo-controlled treatment period.  ICS and LABA dosing must be kept stable from screening through the end of the study.

For Further Information, contact Shannon Flowers, RN; 615 936-5841 

        

Asthma Research

A number of basic and clinical research endeavors are exploring the mechanisms and treatment of asthma. Some of the projects are wholly contained within the Division of Allergy, Pulmonary and Critical Care Medicine; others reside in collaborating departments. The following paragraphs contain a partial list of investigators and their research interests which intersect the human disease syndrome of asthma.
  1. Role of Prostaglandin E2 in Asthma.
      Dr. Stokes Peebles - Division of Allergy, Pulmonary and Critical Care Medicine
      Dr. Richard Breyer - Division of Nephrology
  2. This NIH funded effort will determine the effect of a naturally occurring compound, PGE2, on the immune inflammation characteristic of asthma is spearheaded by Dr. Stokes Peebles. The research program examines the effect of PGE2 in mice with generic alteration in their PGE2 receptors.
  3. Viral Infections and Asthma
      Dr. Stokes Peebles - Division of Allergy, Pulmonary and Critical Care Medicine
      Dr. Tina Hartert - Division of Allergy, Pulmonary and Critical Care Medicine

    This NIH funded area of investigation also uses basic investigations into the interaction of RSV viral infection and allergic sensitization in a manner directly relevant to human asthma. These studies have confirmed that the timing of RSV infection is critical for its effect in either creating or preventing allergic asthmatic responses. Studies in human asthma with spontaneous viral infections are planned.

  4. Molecular Mechanisms of Immune Deviation and Memory
      Dr. Mark Boothby - Division of Rheumatology and Clinical Immunology
      Dr. James Sheller - Division of Allergy, Pulmonary and Critical Care Medicine

    Research in this NIH funded project is aimed at explaining the molecular mechanisms by which T lymphocytes become "allergic", and how the subsequent re exposure to allergen enhances immunologic responses. A variety of transgenic approaches to key questions have been developed, together with methodology for physiologic endpoints of airway hyperresponsiveness characteristic of asthma.

  5. Asthma in the Elderly
      Dr. Tina Hartert - Division of Allergy, Pulmonary and Critical Care Medicine
      Dr. Marie Griffin - Division of Preventive Medicine

    This NIH funded project investigates the factors which modify asthma in the elderly, and the key outcome variables important in asthma in the elderly. This previously neglected field of study should provide important insights which will aid in treatment of older asthmatics.

  6. Adenosine Receptors in Asthma
      Dr. Italo Biaggioni - Division of Clinical Pharmacology
      Dr. James Sheller - Division of Allergy, Pulmonary and Critical Care Medicine
      Dr. John Murray - Division Allergy, Pulmonary and Critical Care Medicine, Division of Clinical Pharmacology
    This funded investigation examines the presence of adenosine receptor subtypes on human mast cells and other immune cells, and determines the effect of receptor activation.
  7. Clinical Studies in Asthma and Allergy
      Dr. John Murray - Division of Allergy, Pulmonary and Critical Care Medicine, Division of Clinical Pharmacology

    Many ongoing studies in asthma and hay fever are conducted with pharmaceutical company sponsorship on the effects of various compounds on asthma and allergic diseases. Volunteers are continually being sought and are compensated for their participation.

    The isoprostanes are non enzymatically formed eicosanoid products discovered by Dr. Jack Roberts. They are indicators of oxidant reactions, and also possess potent biologic effects. Their possible role in allergic airway diseases is unknown, but will be the focus of investigations in human asthma and in more basic investigation.

  8. Oxidative Stress in Allergic Inflammation
      Dr. James Sheller
      Dr. Megha Talati
      Dr. Jack Roberts
      Dr. Jay Jerome
      Dr. Ray Mernaugh

    Using a murine model of allergic inflammation, the role of oxidative stress in airway inflammation is being investigated with funding from the Sandler Program for Asthma Research. Key to this undertaking is the quantification of isoprostanes, which are non enzymatically formed eicosanoid products discovered by Dr. Jack Roberts. They are indicators of oxidant reactions, and also possess potent biologic effects. Immunochemistry means for localizing these compounds to individual cells, matrix and subcellular locations have been developed, using confocal microscopy, electron microscopy and analytical software.

    1. Asthma Disparities in Cohorts at Risk for Morbidity
        James Sheller
        Tina Hartert
        Paul Moore
        Neal Patel
        Mike Stein
        Bill Cooper

    This NIH funded undertaking is a joint venture with Meharry Medical College intended to address the origin and treatment of asthma disparities in minority populations. Asthma appears to be more severe in African-Americans. Four projects conducted jointly at Meharry and Vanderbilt will examine the role of disparities in pregnant asthmatics, the effectiveness of interventions in pregnant minority asthmatics, the role of beta adrenergic receptor polymorphisms in childhood asthma, and finally to determine the role of symptom description and perception in asthma disparities.
    NIH HLBI 1 U01 HL 072471-02
    Web Site: http://www.mc.vanderbilt.edu/root/vumc.php?site=mvadc

    Cystic Fibrosis

    The majority of Cystic fibrosis (CF) patients now survive beyond childhood, and CF related diabetes (CFRD), due to insulin deficiency, is common. CFRD without fasting hyperglycemia is found in 25% of CF adults and is associated with increased morbidity and mortality. BMI and pulmonary function deteriorate much more rapidly in these patients than in CF patients with normal glucose tolerance. Insulin deficiency alters protein and fat metabolism resulting in loss of weight and lean body mass and contributing to pulmonary disease and clinical decline.

    Preliminary data have shown that insulin and, to a lesser extent, the oral diabetes agent repaglinide acutely improve protein synthesis in patients with CFRD without fasting hyperglycemia. If it can be shown that insulin or repaglinide also imp[roves body mass and pulmonary function, it would have a major impact on the current therapy and prognosis for adult CF patients. (Taken from protocol by Antoinette Moran MD, Principle Investigator/ Program Director UM). We are currently enrolling patients for this study who are male or female, over the age of 16 who are done growing and have cystic fibrosis. A two hour oral glucose tolerance test is required. Patients who qualify must have a normal fasting glucose level (<126) and a 2hour glucose level above 200. Tolerance test must be done while patient is in stable health, with no evidence of acute infection in 2 months. Weight must be stable within 5% during the previous 3 months. Patient must be willing to come to clinic every 3 months, and engage in weekly phone contacts. Also, patient must be able to give informed consent.

    Bonnie Slovis MD, Principle Investigator /VUMC
    Susan France RN BSN, Study Coordinator /VUMC
    Phone 615-322-3048

    Familial Idiopathic Pulmonary Fibrosis (FIPF)

    FIPF is a specific form of pulmonary fibrosis that occurs in families (familial). Many families have had 5 or more patients and unfortunately one family has suffered 15 IPF patients. IPF affects only the lungs (pulmonary), and causes the growth of new fibrotic tissue (fibrosis) which cannot be attributed to any other disease or environmental factor (idiopathic). It is an illness in which the alveoli (air sacs) and interstitium (tissue between the air sacs) of the lungs are replaced by scar.

    IPF usually affects both lungs with scar and inflammation, which begin at the bottom of the lung at the outside surface (the pleura) and then subsequently move upward and inward. As the disease progresses, the increased scar tissue makes the lungs shrink in size and limits their ability to transfer oxygen from the alveoli into the blood. Even common tasks like walking up a slight hill, dressing, or climbing stairs can lead to breathlessness. As the disease progresses disabling shortness of breath may develop.

    IPF is uncommon, affecting somewhere between 13-30 of every 100,000 people in the U.S. Estimates of the prevalence of familial IPF suggest that about 2% of all cases are familial, but our evidence suggests that a genetic factor may contribute much more often. The disease appears to be more common in men than in women, and can be passed from either parent to children of either gender. It tends to occur in people between the ages of fifty and seventy, but it can occur much younger, even in children, especially when it occurs in families. The primary goal of our study is to find the gene(s) that causes IPF.

    Because the normal lung has substantial reserve capacity, the disease can progress significantly before symptoms begin, so by the time many patients with IPF recognize symptoms and go to see their doctor, the disease may already have caused considerable scarring and loss of lung function. Typically patients experience shortness of breath on exertion as the first symptom. Other early signs and symptoms may include a persistent hacking dry cough, fatigue, mild fever, and weight loss. It is not yet known how long the disease can be present in a silent form before symptoms develop. If a test which could identify such a pre-symptomatic state could be found, then it might be possible to treat patients before such extensive lung damage occurred. Discovering such a test is another goal of our research.

    There is not yet a known cure for IPF, but several multicenter treatment trials which are underway now provide hope that an effective treatment will be found soon, and lung transplantation is possible for some patients. It is estimated that there are about 50,000 patients suffering from IPF in the US. The median survival in groups of patients is only about 3 years, but there is a wide range, with some patients living a decade or more, while others progress rapidly over a few months to respiratory failure. In patients with IPF, symptoms often begin or worsen during common respiratory viral infections, but it is unclear whether viruses contribute in a decisive way to the development or progression of IPF.

    Because of advances being made in identifying pre-symptomatic patients with early disease and because of new drug trials, we are interested in identifying individuals at risk for IPF. A complete medical history is essential for diagnosis to exclude other known causes of interstitial lung diseases. IPF belongs to a family of about 150 similar interstitial lung diseases (ILDs), so its diagnosis can only be made after excluding all other causes. Because of its many similarities, IPF may be misdiagnosed or confused with other conditions. In order to properly diagnose IPF, a doctor may order a chest x-ray, CT scan, pulmonary function test, bronchoscopy, surgical lung biopsy, and various blood tests. Sadly, IPF is usually ultimately disabling and life threatening. We are pursuing a better understanding of the natural history of IPF and investigating potential risk factors that may make a person more susceptible to IPF which we hope will lead to new treatments.

    For more information contact:

    Cheryl Markin, Coordinator
    James Loyd, M. D., Director
    T-1217 MCN
    Vanderbilt University Medical Center
    Nashville, TN 37232-2650
    Local call 1-615-322-2077
    Toll Free Long distance 1-888-898-1550
    cheryl.markin@mcmail.vanderbilt.edu

    Familial Pulmonary Arterial Hypertension (FPAH) and Idiopathic Pulmonary Arterial Hypertension (IPAH)

    IPAH is high blood pressure (hypertension) within the lungs (pulmonary) of unknown cause (idiopathic)  It is a disease that begins by blocking the very smallest arteries (blood vessels) throughout the lungs. The blood vessels that are affected are about the size of a human hair. However, they are very important because all of the blood in the circulation must pass through them. When many blood vessels become blocked then blood cannot flow normally through the lungs. Consequently, blood flow to the rest of the body is inadequate.

    Familial Pulmonary Arterial Hypertension (FPAH) Study: https://medschool.vanderbilt.edu/pah/

    Vanderbilt University Medical Center
    Nashville, TN 37232-2650

    James Loyd, M.D., Director
    Lisa Wheeler, Coordinator
    John Newman, M. D., Pulmonary Medicine
    John Phillips, III, M. D., Medical Genetics
    Joy Cogan, Ph. D., Medical Genetic
    Eric Austin, MD, Pediatric Pulmonary

    General Information about FPAH

    The incidence of IPAH in the general population is about 1-2 per million. An NIH study of nearly 200 patients conducted at 30 US medical centers in the 1980's showed that only 6% of these patients had a family history of PAH. Symptoms, clinical course, and response to therapy of FPAH patients is similar to those with IPAH . The disease can be inherited from a male or female parent. The incidence is 2.4:1 females to males, similar to the general IPAH population. FPAH is inherited as a dominant trait, although, many persons who carry the gene do not get the disease. A gene that causes FPAH, bone morphogenetic protein receptor 2 (BMPR2) was discovered and described in 2000 by Vanderbilt University and Columbia University researchers, independently. This gene is associated with cell growth and development. "Mistakes" or mutations of this gene may lead to the formation of abnormal pulmonary arteries seen in this disease.

    Current Therapy and the Pulmonary Hypertension Clinic

    Diagnosis and treatment of PAH is provided by the Vanderbilt Pulmonary Hypertension Clinic (PHC).  With over 10 years of experience in treating this disease and participating in most clinical trials for new therapies the clinic is quite experienced in helping patients deal with this devastating diagnosis.  An active lung transplant program is also available to patients who are interested and eligible for this alternative to traditional therapy.

    Many new treatments have been developed over the last several years including prostacyclins, endothelin receptor antagonists (ERA), and phophodiesterase inhibitors.  Prostacyclins work by opening blood vessels a process called vasodilation. FDA approved prostacyclins are Flolan, Remodulin, and Ventavis.  The endothelin receptor antagonists prevent vessels from constricting or narrowing.  Tracleer and Letairis are the approved ERAs.  The phosphodiesterase inhibitors, Sildenafil-trade name Revatio, help relax blood vessels leading to vasodilation using a pathway different from the prostacyclins.  The clinic team has experience with all of these therapies and continues to participate in studies of new potential treatments. 

    Vanderbilt PHC
    Ivan Robbins, MD, Director
    Kimberly Farmer, RN, Nurse Coordinator
    Amy Mullican, RN, Nurse Coordinator
    Tracy Oyler, RN, Research Nurse
    Janet Morris, Administrative Assistant
    615-322-6512
    The Vanderbilt Pulmonary Hypertension Clinic
    B817, TVC
    Nashville TN 37232-5735

    The Pulmonary Hypertension Association is a non-profit organization that has been pivotal in providing information for patients and physicians.  They have been a wonderful partner in support of our research.  Please contact them for more general information and to become involved in the fight against PAH. 

    Pulmonary Hypertension Association (PHA) and the PATHLIGHT:

    PHA is primarily a volunteer support group for patients with pulmonary hypertension of any cause. The group is administered by PAH patients and their families. They provide education for patients and physicians about the disease. They also have a nationwide system of support groups and maintain a listing of physicians experienced with treating PAH. Contact them at following address and phone:  Pulmonary Hypertension Association
    801 Roeder Road, Suite 400
    Silver Spring, MD 20910
    1-800-748-7274
    www.phassociation.org

    PHA publishes a quarterly newsletter, The PATHLIGHT, that offers many articles of interest to patients and family members.  Additionally, the organization publishes a medical journal, Advances in Pulmonary Hypertension, that is distributed to cardiologists, pulmonologists, and rheumatologists nation wide.

    References
    Genetics and Mediators in pulmonary arterial hypertension. Austin ED, Loyd JE. Clinics in Chest Medicine. 2007 Mar;28(1):43-57, vii-viii. Review.

    Narrative review: the enigma of pulmonary arterial hypertension: new insights from genetic studies. Newman JH, Phillips JA III, Loyd, JE, Annals of Internal Medicine. 2008 Feb 19; 148(4): 278-83. Review

    What patients and their relatives think about testing for BMPR2. Jones DL, Sandberg JC, Rosenthal MJ, Saunders RC, Hannig VL, Clayton EW.J Genet Couns. 2008 Oct;17(5):452-8.

    Mutation in the gene for bone morphogenetic protein receptor II as a cause of primary pulmonary hypertension in a large kindred Newman, J.H., Wheeler, L., Lane, K.B., Loyd, E., Gaddipati, R., Phillips, J.A. III, Loyd, J.E..N. Engl. J. Med. 345:319-24, 2001.

    Heterozygous germline mutations in a TGF-beta receptor, BMPR2, are the cause of familial primary pulmonary hypertension. Lane, K.B., Machado, R.D., Pauciulo, M.W., Thompson, J.R., Philips, J.A. III, Loyd, J.E., Nichols, W.C., Trembath, R.C. ,Nature Genetics. 2626(1):81-84, 2000.

    ICU Delirium and Cognitive Impairment

    Awakening and Breathing Controlled (ABC) Trial
    PI: Wes Ely, MD, MPH

    Co-Investigator and Contact Person: Tim Girard, MD
    timothy.girard@vanderbilt.edu

    Study Nurse: Jan Dunn, RN, MSN

    Enrollment is currently open
    The purpose of this study is to determine the impact of a new RN/RRT (Registered Nurse/Registered Respiratory Therapist) directed 2-step protocol to wean patients off of a ventilator. This protocol involves daily attempts to halt sedation (spontaneous awakening trials) combined with daily assessments of patients readiness to wean from mechanical ventilation (spontaneous breathing trials). A secondary aim of this study is to evaluate the patients for long-term cognitive impairment.

    MENDS Study
    PI: Wes Ely, MD, MPH

    Co-Investigator and Contact Person: Pratik Pandharipande, MD
    pratik.pandharipande@vanderbilt.edu

    Study Nurse: Jennifer Frizzell, RN, BSN

    Enrollment is currently open
    Delirium has recently been shown as a predictor of death, increased cost, and longer length of stay in ventilated patients. Sedative and analgesic medications relieve anxiety and pain, but may contribute to patients transitioning into delirium. It is possible that modifying the paradigm for sedation using novel therapies targeted at different receptors, such as dexmedetomidine targeting alpha2 receptors and sparing the GABA receptors, could provide efficacious sedation yet reduce the development, duration, and severity of acute brain dysfunction (delirium). This study focuses on comparing sedation achieved with alpha2 agonists and benzodiazepines.

    MIND Study Modifying the INcidence of Delirium
    PI: Wes Ely, MD, MPH

    Co-Investigators: Pratik Pandharipande, MD
    Tim Girard, MD

    Study Nurse and Contact Person: Mandy Fraley, RN, BSN
    Miranda.l.fraley@vanderbilt.edu

    Enrollment is currently open
    Delirium is associated with increased risk of death, prolonged stay, higher cost of care, and likely long-term brain deficits in survivors. This form of brain dysfunction occurs in intensive care unit (ICU) patients in epidemic proportions, and the scope of this problem is likely to worsen in upcoming years due to the aging of our population and increased utilization of the ICU. Currently, delirium goes unrecognized and untreated in the vast majority of circumstances in the ICU unless the patient presents with hyperactive delirium and agitation. In the latter circumstance, a commonly used typical antipsychotic called haloperidol is considered the principal agent for treating delirium based largely on anecdotal evidence to support its usefulness, though no placebo controlled trials exist. There are no FDA approved medications for delirium. The objective of this study is to determine whether typical or atypical antipsychotics reduce the incidence and duration of delirium in high-risk mechanically ventilated patients as compared to placebo.

     

    Idiopathic Pulmonary Fibrosis (IPF) Clinical Trials

    Bosentan (Tracleer)
    A Double-Blind, Randomized, Placebo-Controlled Multicenter Study to assess the Efficacy, Tolerability and Safety of Bosentan in Patients with Idiopathic Pulmonary Fibrosis. PI: Dr. Lisa H. Lancaster.

    A world wide study to demonstrate improvement in functional capacity, as measured by the six-minute walk, in patients with IPF. The duration of this placebo-controlled study will be a minimum of 12 months. Patients included are those diagnosed with IPF within three years, older than 18 years, and who have a worsening of disease condition. Evaluations will be screening/baseline, Month 1, Month 3, and every three months until the end of the study. Bosentan or placebo will be given orally twice daily. Enrollment is closed worldwide. For more detailed information, please contact Wendi Mason, RN, ACNP, at 615-343-7068, or wendi.mason@vanderbilt.edu.

    Etancercept (Enbrel)
    A Double-Blind, Parallel, Placebo-Controlled, Randomized Study of the Efficacy and Safety of Etanercept in Patients with Idiopathic Pulmonary Fibrosis. PI: Dr. Lisa H. Lancaster.

    A one-year placebo-controlled study to evaluate the safety and efficacy of etanercept (a recombinant human tumor necrosis factor alpha soluble receptor that blocks binding to cell surface receptors) in patients with IPF. Patients included are those diagnosed with IPF within the past 24 months, 40 to 80 years old, and who have progressive disease despite standard of care. Evaluations will be performed by the PI at screening/baseline, Week 2, Week 4, and every 4 weeks for one year. Etanercept or placebo will be injected by the patient/support person under the skin twice per week. 100 patients will be enrolled study wide. Enrollment is closed. For more information, please contact Wendi Mason, RN, ACNP, at 615-343-7068, or wendi.mason@vanderbilt.edu.

    Imatinib mesylate (Gleevec)
    Phase II, Randomized, Double-Blind Placebo Controlled Study of the Safety and Clinical Effects of Gleevec (imatinib mesylate) Administered Orally to Patients with Idiopathic Pulmonary Fibrosis. PI: Dr. Lisa H. Lancaster

    A placebo-controlled study being completed in the United States to evaluate disease progression in patients with IPF. Patients included are those diagnosed with IPF within three years, aged 20-79, and who have exhibited a worsening in their disease. Evaluations will be screening/baseline, rather frequently until Week 16, then every two months for two years. Gleevec 600 mg or placebo is taken once daily by mouth. Enrollment is ongoing at Vanderbilt. For more information please contact Wendi Mason, RN, ACNP, at 615-343-7068, or wendi.mason@vanderbilt.edu.

    Interferon gamma-1b (Actimmune)
    A Randomized, Double-Blind, Placebo-Controlled, Multinational, Phase III Study of the Safety and Efficacy of 200mcg Subcutaneous Interferon gamma-1b (IFN-y 1b) in Patients with Idiopathic Pulmonary Fibrosis. PI: Dr. Lisa Lancaster

    A worldwide study that plans to enroll 600 IPF patients across 60 centers to demonstrate longevity. The study will be placebo-controlled with patients receiving either interferon gamma or placebo three times a week subcutaneously. Patients are those diagnosed within three years, aged 40-79, and have worsened over the last year. Evaluations occur at screening, baseline, every two weeks for six weeks, then every six weeks for six months, and then every three months for the length of the study. The study will last two years from the time that Patient 600 is enrolled. We anticipate the study to last a total of four years. Enrollment is ongoing. For more information please contact Wendi Mason, RN, ACNP, at 615-343-7068, or wendi.mason@vanderbilt.edu.

    Lung Cancer RESEARCH PROGRAM:

    Investigators:

    Pierre Massion, M.D.
    Timothy Blackwell, MD
    Alison Miller, MD
    Jamshedur Rahman, PhD
    Vasiliy Polosukhin, MD, PhD
    The Damon Runyon Clinical Investigator Award (Massion)

    07/01/03 - 06/30/08
    "Proteomic Approach for Risk Assessment of Lung Cancer"The goal of this project to identify in bronchial biopsies protein profiles that discriminate smokers from non- smokers and smokers with lung cancer from smokers without lung cancer, to identify in the plasma protein patterns predictive of lung cancer development, and to determine the prevalence of specific proteins identified in normal airways and in lung cancer. 1 R01 CA 102353-01A2 (Massion) 

    03/01/05 - 02/28/09
    NIH/NCI"Molecular Approaches to Early Detection of Lung CancerThe goal of this proposed project is to use biomarkers predictive of cancer development to detect lung cancer while cure remains possible.  The project proposes to interrogate the human model of squamous tumorigenesis by genetic and protein approaches.  The project will focus on chromosome 3q region of genomic amplification, identify candidate genes involved in tumorigenesis and test their potential role as biomarkers predictive of lung cancer development. Project 1 from SPORE in Lung Cancer" (Massion)

    01/01/07 - 12/31/11
    "Molecular predictors of lung cancer progression"5 P50 CA 090949 (Carbone PI)NIH/NCIThe central hypothesis of this proposal is that early during their development tumors develop molecular determinants that one could identify before the invasive stage and that these specific determinants may be used as biomarkers for the early detection of lung cancer.  We propose to take a proteomic approach using matrix assisted laser desorption ionization mass spectrometry (MALDI-MS) to study the molecular determinants of tumor progression in the airways and in the serum of high-risk individuals. 1 R01 LM 007948-01 (Aliferis)

    08/01/03 - 07/31/06
    National Library of Medicine
    Principled Methods for Very-Large-Scale Causal Discovery"We proposed to apply and evaluate our local large-scale causal discovery methods to three problem datasets that span bioinformatics, epidemiology, and clinical medicine.  We also plan to compare our methods to a large array of major state-of-the-art techniques for causal discovery (including major heuristic methods, and, when practically applicable, methods that are based on formal causal foundations). 1 U01 CA 114771-01 (Carbone)

    03/13/05 - 03/31/10
    NIH/NCI"Molecular Signatures of Lung Cancer" SPECS grantRole on Project:  InvestigatorThis application proposes a partnering of premiere institutions based in the Lung Cancer SPORE Program to determine how the information derived from comprehensive molecular analyses can be used to improve patient care and ultimately, patient outcomes. 1 R33 CA 116123-01 (Chaurand)

    07/01/05 - 06/30/08
    NIH/NCI"Preparation of Cancer Tissues for MS Imagingof Proteins"This study proposes to optimize the methodologies allowing MALDI MS analysis of fresh frozen sections, to developand validate new approaches to investigate by MS solvent fixed biopsies, measure pharmaceutical compounds by MS and validate protocols allowsing MA analysis of cancer cells in fine needle aspirates.  5 P50 CA 070907-08 (Massion,  Miller)

    07/01/03 - 06/30/08
    NIH/NCI (Univ. of Texas subcontract)"SPORE in Lung Cancer - LCBCC Sup.The purpose of this multicenter study is to evaluate the benefit of ILOPROST as a chemopreventive agent for lung cancer in patients presenting with sputum atypia.  ASCO Advanced Clinical Research Award (ACRA) in Lung Cancer

    07/01/07 - 06/30/10
    P.I.:  Massion"Tumor specific antibodies for lung cancer diagnosis"A promising approach for the discovery of diagnostic cancer biomarkers is the identification of panels of tumor antigens that elicit an antibody response.  The goal Dr. Massion is pursuing is to identify novel diagnostic biomarkers of lung cancer with a novel strategy that uses an antibody library to capture specific markers of lung cancers. VUMC Discovery Grant: (PI: Massion) 

    07/01/2007-06/31/2009
    Role of Polyimmunoglobulin Receptor Expression in the Pathogenesis of COPD Surveillance of high risk individuals for lung cancer. (Miller, Massion)

    07-01-07-onProject involves epidemiological and translation research on the role of preinvasive lesions and COPD to estimating the added risk to develop lung cancer . 

    Lung Transplant Clinical Trials

    A Phase III, Randomized, Double Blind Comparison of Oral Valganciclovir and Placebo for Prevention of CMV Infection After Lung Transplantation (still in IRB committee)

    A Multicenter Study Examining the Role of Protein C (activated) in early respiratory distress syndrome (ARDS)
    Lung Transplant Tissue Bank

    For questions or enrollment for the studies listed above please contact:
    Jean Barnes, RN,
    Research Coordinator
    VUMC Lung Transplant Program
    615-936-0393.

    Pulmonary Arterial Hypertension Clinical Trials in Progress

    Encysive FPH03
    A long term, open label study to evaluate safety of Sitaxentan Sodium treatment in patients with PAH.
    No longer enrolling. Pending FDA approval

    Reveal Actelion
    The REVEAL Registry™ is a multicenter, observational, U.S.-based study of the clinical course and disease management of pulmonary arterial hypertension (PAH) patients. All consecutive consenting patients diagnosed with WHO Group I PAH according to specific hemodynamic criteria at participating institutions will be enrolled. Participating patients will be followed for a minimum of five years from the time of enrollment.
    Expected Total Enrollment:  3000;  Study start: March 2006; Expected completion: December 2012

    United Therapies, Freedom 301, 304 
    This study is an international, multi-center, randomized, double-blind, placebo-controlled study in subjects with PAH who are currently receiving approved therapy for their PAH (i.e., endothelin receptor antagonist and/or phosphodiesterase-5 inhibitor). Study visits will occur at 4 week intervals for 16 weeks with the key measure of efficacy being the 6-minute walk test. Study procedures include routine blood tests, medical history, physical exams, disease evaluation, and exercise tests. One optional substudy is also a part of FREEDOM-C at select centers - a hemodynamic substudy with a right heart catheterization at Baseline and Week 16. Patients who complete all assessments for 16-weeks will also be eligible to enter a 36 month open-label, extension phase study (FREEDOM - 304).  Study Start April 2007- Expected completion: February 2011 

    To refer a patient for an appointment in our Pulmonary Hypertension Clinic or to speak with a nurse coordinator regarding these studies please contact: Teresa Welch-Burke, at 615-343-8277 or by email at Teresa.Welch-Burke@vanderbilt.edu.   

    Severe Sepsis Trials

    Sepsis is a syndrome characterized by an overwhelming systemic response to infection, which can rapidly lead to organ dysfunction and ultimately death. Sepsis may cause multiple organs in the body to fail and may trigger the onset of both abnormal clotting and bleeding. Every day, sepsis results in the death of more than 1,400 people worldwide and is the leading cause of death in noncoronary intensive care units. The estimated costs associated with the treatment of patients with sepsis are $17 billion annually in the United States. Over the past 20 years we have been involved with sepsis research with a variety of pharmaceutical agents. The following is a list of trials starting with the most recent;

    Enhance Trial - The Open Label Study of Recombinant Human Activated Protein C in Severe Sepsis, A Phase 3b Clinical Trial

    Compassionate Use (Treatment Use) Study with Recombinant Human Activated Protein C in Severe Sepsis

    PROWESS study - A Phase III Study to Determine the Efficacy and Safety for Recombinant Human Activated Protein C in Severe Sepsis

    A Phase II study to Determine the Safety, Pharmacokinetics, and Effective Dose Range and Dosing Duration for Recombinant Activated Protein C in Severe Sepsis.

    Cardiopulmonary Effects of Ibuprofen in Human Sepsis - Multicenter, Randomized, Placebo Controlled, Phase III Study of Intravenous Ibuprofen.

    Ibuprofen in Sepsis Syndrome - Multi-center, Randomized, Placebo Controlled, Phase II Study of Rectally Administered Ibuprofen.

     

    Vanderbilt Clinical Trials Coordinating Center

    The Center for Lung Research, in the Division of Allergy, Pulmonary and Critical Care Medicine, maintains an active clinical coordinating center (VCC) design to support virtually all aspects of the conduct of clinical trials in pulmonary and critical care.

    The VCC is staffed with a biostatistician, fulltime clinical research-oriented physician scientists, biomedical engineers, computer scientists and highly trained research nurses. The Center has been involved in the conduct of dozens of major national and international clinical trials over the past 18 years. For most of its existence, the major focus of the VCC has been trials of agents and techniques with potential value in the diagnosis or treatment of sepsis and the acute respiratory distress syndrome. More recently, the Center has broadened its scope to include asthma, primary and secondary pulmonary hypertension, interstitial pulmonary fibrosis and pulmonary diseases associated with bone marrow transplantation.

    The resources available within the VCC include scientific study design, protocol development, clinical center selection and training, data collection, data analysis, clinical coordination, study drug distribution and tracking, study monitoring, report generation, manuscript preparation, interactions with the Food and Drug Administration and coordination of investigators meetings for multi-center trials. A local web site is maintained to facilitate study coordination. The VCC has participated in all aspects of Phase I, II and III trials.

    For more information please contact: Gordon R. Bernard, M.D.
    Professor of Medicine
    Director, Division of Allergy, Pulmonary and Critical Care Medicine

    Vanderbilt University Medical Center
    Allergy, Pulmonary and Critical Care Medicine
    1161 21st Ave. S., Suite T-1218 MCN
    Nashville TN 37232-2650
    Office: (615) 343-0077
    Fax: (615) 343-4479
    E-mail: Gordon.Bernard@vanderbilt.edu


    Basic Science Research Programs

    Asthma Research

    Oxidant Stress in Murine Allergic Inflammation

    Dr. L. Jackson Roberts, II. Div of Clinical Pharmacology
    Dr. J.R. Sheller,
    Dr. T. Blackwell
    Dr. Megha Talati
    Daphne Mitchell, B.S.

    The role that oxidant stress might play in allergic inflammation is being examined in a murine model funded by the Sandler Program for Asthma Research. Using immunostaining for the lipid peroxidation products discovered by Dr. Roberts, the isoprostanes, evidence has been provided for the cell specific oxidant stress occurring in the ovalbumin model of allergic inflammation.

    Asthma Disparities

    Dr. J.R. Sheller
    Dr. Tina Hartert
    Dr. Neal Patel, Pediatric Anesthesia
    Dr. Paul Moore, Pediatric Pulmonology
    Dr. Marie Griffith, Preventive Medicine
    Dr. William Cooper, Pediatrics
    Dr. Rhonda BeLue, Meharry Medical College
    Dr. Michael Stein, Clinical Pharmacology

    This NIH funded Center for Asthma Disparities is a collaborative undertaking with Meharry Medical College. The Center will investigate the mechanisms by which blacks have more severe asthma than whites, and will elucidate ways to improve treatment of black asthmatics.