Current Sponsored Clinical Trials

Title: Intervention Study in Overweight Patients with COPD (INSIGHT COPD)

   PI: Anupama Tiwari, MD

   Funded by: NIH to University of Pittsburgh.

   Currently recruiting COPD patients

Approximately 70% of patients with Chronic Obstructive Pulmonary Disease (COPD) are obese or overweight. Tobacco smoking that causes COPD also is associated with other poor health habits that can lead to obesity and cardiovascular disease. Symptoms of COPD are often non-specific and include dyspnea and exercise intolerance. COPD treatment guidelines recommend stepped escalation of inhaled medications to improve these symptoms, but make little mention of the effect of co-existing obesity or weight loss interventions because of insufficient evidence. Cardiovascular disease is a leading cause of mortality among patients with COPD, and obesity is associated with important risk factors for cardiovascular disease including dyslipidemia, hypertension, and diabetes. Comprehensive lifestyle interventions that include calorie-controlled healthy eating, increased physical activity, and behavioral self-management strategies consistently result in modest, clinically significant weight loss and associated reductions in cardiovascular risk factors. That overweight and obese patients with COPD would reap similar clinical benefits from modest weight loss is an intuitive - but untested - concept. Therefore, we are conducting a multicenter, patient-level randomized, pragmatic clinical trial to produce first-ever data on the effectiveness of an evidence-based self-directed lifestyle intervention for 12 months targeting modest weight loss and increased physical activity among overweight and obese patients with COPD. We are serving as a Protocol Leadership Group (PLG) for the National Heart, Lung, and Blood Institute's (NHLBI) "Multi-Site Clinical Trials for the Pulmonary Trials Cooperative (PTC)" in order to test if intervention participants have better outcomes through 18 months of follow-up compared to usual care control patients in terms of weight loss and exercise tolerance using the 6-Minute Walk Test. Secondary outcomes include dyspnea using the modified Borg scale, generic health-related quality of life using the SF-12v2, and major cardiovascular risk factors using Framingham risk score, central obesity by waist circumference, and blood pressure. We will oversee enrollment of approximately 1000 patients at multiple clinical sites, chosen and contracted by the PTC's Network Management Core (NEMO). As the PLG for the INSIGHT COPD trial, we will cooperate with NEMO and will provide trial oversight, and data management and reporting.

Title: A Multicenter,Randomized, Double-blind, Parallel Group, Placebo-controlled, Phase 3b Study to Evaluate the Safety and Efficacy of Benralizumab 30 mg sc in Patients with Severe Asthma Uncontrolled on Standard of Care Treatment (ANDHI)

     PI: Arjun Mohan, MD

     Sub I: Veeranna Maddipati, MD and Mary Jane Thomassen, PhD

     Funded by: Astra Zeneca

     Recruitment begins November 2017

Study design

This is a Phase 3b, randomized, double-blind, placebo-controlled, parallel-group study designed to evaluate the efficacy and the safety of repeat dosing of benralizumab 30 mg subcutaneous (sc) versus placebo on top of standard of care asthma therapy in patients with severe uncontrolled asthma. Approximately 800 patients with peripheral blood eosinophil counts ≥300 cells/μL will be randomized to receive benralizumab 30 mg sc or matched placebo for 24 weeks.

After enrollment, eligible patients will enter a 42-day screening/run-in period. Patients who meet eligibility criteria will be randomized 1:1 on Day 0 to receive either benralizumab or placebo every 56 days (every 8 weeks) through Week 16, with end-of-treatment (EOT) at Day 168 (Week 24). The initial dose of benralizumab will be followed by a single loading dose of benralizumab 30 mg sc or placebo at Day 28 (Week 4) consistent with tested Phase 3 dosing regimen. This dose and regimen was previously confirmed to be effective in Phase 3 asthma studies with an overall safety profile similar to placebo, and conforms to the anticipated posology for regulatory approval. A follow-up (FU) visit for final safety assessment will be conducted at Day 182 (Week 26).

Title: Registry for Advanced Sarcoidosis (ReAS)

   PI: Ogugua Obi, MD, MPH, MSc (Epid)

   Sub I: Veeranna Maddipati, MD

   Funded by: University of Cincinnati and Mallinckrodt Pharmaceuticals

   IRB approval pending - will open for enrollment November 2018

Background and significance: The clinical outcome of sarcoidosis is variable. While over half of patients have resolution of their disease within two years of diagnosis, at least a quarter of patients will have chronic disease requiring therapy for more than five years. 2;3 Certain manifestations of sarcoidosis are associated with chronic disease. These include pulmonary fibrosis, neurologic and cardiac disease, lupus pernio, and those requiring treatment. 4;5 Recent genetic markers have been associated with advanced sarcoidosis. 6;7 Most of these studies are based on evaluating patients at single time points. In addition, they lack control sarcoidosis patients who have been matched for race, age, and gender. The use of potent agents such as infliximab have proved useful in treating advanced sarcoidosis. 8;9 This treatment regimen is associated with significant cost and requires careful monitoring. 10 Other potent agents have also been used for advanced sarcoidosis, including adalimumab, rituximab, cyclophosphamide, and Acthar. 11-13 This registry will determine the risk factors for chronic disease and natural course of these manifestations.

Title: Registry of Sarcoidosis Associated Pulmonary Hypertension (ReSAPH)

    PI: Veeranna Maddipati, MD

    Sub I: Ogugua Obi, MD, MPH, MSc (Epid)

    Funded by: University of Cincinnati – Investigator Initiated

    IRB approval pending – will open for enrollment November 2018

In sarcoidosis, respiratory failure is the major cause of death. Reduced lung volume is a predictor for the at risk patient. Among patients with low vital capacity, the presence of pulmonary hypertension and elevated right atrial pressure are the best predictors of early mortality.  

There have been several single case reports of pulmonary hypertension, including therapy for pulmonary sarcoidosis. There have been a limited number of prospective studies of any group of sarcoidosis patients, because of the need for catheterization to confirm the diagnosis.

On the other hand, pulmonary hypertension may be relatively common in sarcoidosis patients. In a prospective study of pulmonary sarcoidosis, over 70% had significant changes in their right ventricle ejection fraction with exercise, suggesting pulmonary hypertension. The cause of pulmonary hypertension in sarcoidosis is multi-factorial, including diastolic dysfunction, vessel compression by adenopathy, lung destruction by fibrosis, and granulomatous vasculitis.

With the advent of new vasodilator drugs effective for pulmonary hypertension, interest has risen in treating pulmonary hypertension due to secondary causes, including sarcoidosis. To date, studies have usually been limited to one or two centers with minimal long term follow up for patients begun on therapy.

We have joined a multi-center registry of sarcoidosis associated pulmonary hypertension (SAPH). With this registry, we will characterize the demographics, clinical course, hemodynamics, pulmonary physiology, and disease management of sarcoidosis associated pulmonary hypertension on the United States. We will also compare these features to non-US sites.

Title: A Double-Blind, Placebo-Controlled Trial of Oral Riociguat for Sarcoidosis Associated Pulmonary Hypertension (RioSAPH)

       PI: Veeranna Maddipati, MD

       Sub I: Ogugua Obi, MD, MPH, MSc (Epid)

       Funded by: University of Cincinnati and Bayer HealthCare

       IRB approval pending - will open for enrollment November 2018

Pulmonary hypertension has been described in patients with sarcoidosis, especially those awaiting a lung transplant. In transplant patients, elevation of right atrial pressure and pulmonary artery pressure is associated with the highest mortality while awaiting transplant. The presence of pulmonary hypertension has also been noted in patients with less advanced disease. In a study using exercise MUGA, most patients with pulmonary sarcoidosis had an abnormal right ventricular ejection fraction during exercise, suggesting pulmonary hypertension.

The mechanism of sarcoidosis associated pulmonary arterial hypertension is multifactorial. These include compression of pulmonary vasculature, obliteration of the vessels by fibrosis, and granulomatous vasculitis.

Riociguat has been shown to be a successful treatment for idiopathic pulmonary hypertension and chronic thromboembolic associated pulmonary hypertension. Compared to placebo, it was found to improve the time to clinical worsening (TCW) and six-minute walk distance within twelve weeks of initiating therapy.

The current study is designed to compare Riociguat with placebo in patients with pulmonary arterial hypertension associated with sarcoidosis.  We have partnered with University of Cincinnati and other enrolling centers to undertake this multicenter study. 

Title: A Longitudinal Prospective Observational Study of the Characteristics, Treatment Patterns and Health Outcomes of Individuals with Severe Asthma in the United States (CHRONICLE)

    PI: Arjun Mohan, MD

    Funded by: AstraZeneca.

Asthma is a syndrome characterized by airway inflammation, reversible airflow obstruction,and airway hyper-responsiveness. The majority of asthma patients have mild to moderate disease that can be controlled by low- to medium-dose inhaled corticosteroids (ICS), with or without additional controllers including long-acting bronchodilators, leukotriene modifiers or have severe asthma characterized by a requirement for high-dose ICS plus a second controller (most commonly long-acting beta agonists [LABA]) to prevent it from becoming 'uncontrolled' or that remains 'uncontrolled' despite this therapy. For those whose severe asthma remains uncontrolled, treatment options currently include maintenance use of systemic corticosteroids, treatment with monoclonal antibody therapies that block Type 2 immune responses, or treatment with bronchial thermoplasty. To continue to drive improvements in the understanding and management of severe asthma, there is a need for longitudinal data describing the real-world clinical profile of this patient cohort, their current treatment patterns and associated health outcomes. Real-world data from an unselected population may also enable a better understanding of severe asthma phenotypes and provide insights into more personalized approaches to the clinical management of severe asthma.

The current non-interventional study will collect information on patient demographics, asthma history, relevant comorbidities, asthma treatment patterns, and health outcomes over multiple years from a large, geographically diverse cohort of US patients with severe asthma. The study will include patients with severe asthma who have either experienced frequent exacerbations despite high-dose ICS therapy and additional controllers, require chronic systemic corticosteroids to control asthma symptoms, or are receiving monoclonal antibody treatment for severe asthma.

The primary objective of this study is to describe patient characteristics, treatment patterns, and health outcomes among US adults with severe asthma who are not controlled on high dose ICS with additional controllers and/or require systemic corticosteroid or monoclonal antibody therapy.

Site has been selected - currently under pre - review.  Not open for enrollment.

Title: PAH QuERI Extension Program

     PI: Zia Rehman, MD

     End Date: February 2018

     Enrollment: Closed

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Current Grant Funding

NIH –RO1–  Project Title: Alveolar Macrophage in Granulomatous Disease

   PI – Mary Jane Thomassen, PhD

   Funding Period– 7-1-2016  to 6-30-2021

The current application addresses the environmental health issue of possible carbon nanotube involvement in human granulomatous lung disease.  In particular, sarcoidosis, a proto-typical granulomatous lung disease of unknown cause, has been linked by epidemiologic studies to environmental conditions favoring carbon nanotube formation in ambient air.  Sarcoidosis is also endemic in the coastal areas of the Carolinas and is 4 to 17 times more common in African-Americans than in Caucasians.  This project seeks to utilize a novel murine granuloma model in order to investigate the impact of carbon nanotubes on granuloma formation.  

Dicerna Pharmaceuticals - Project Title: SAA Protein in Multi-Wall Carbon Nanotube (MWCNT) Induced Granulomas

     PI- Mary Jane Thomassen, PhD

     Project ending date: April 2018

Dicerna is developing a pipeline of innovative RNAi therapies using our GalXCTM RNAi platform for the treatment of diseases involving the liver, including rare diseases, chronic liver diseases, cardiovascular diseases and viral infectious diseases

2017 Brody Seed Grant - Project Title: Role of MMP-12 in Fibrosis Progression in a Murine Model of Granulomatous Disease

     PI -Arjun Mohan, MD
     Funding Period:  9-1-2017 to 8-31-2018

Sarcoidosis is a chronic granulomatous disorder that predominantly affects the lung.  The etiology of sarcoidosis is not fully understood.  There is some consensus that certain inciting factors such as infections, organic dusts, carbon nanotubes, etc. trigger a dysregulated immune response.  We developed a murine model of chronic granulomatous pulmonary inflammation by oropharyngeal instillation of multiwall carbon nanotubes (MWCNT) in mice. The robust granulomas formed in this model persist for at least 90 days and are remarkably similar to those seen in sarcoidosis lung. Antigenic Target Protein 6 (ESAT-6) is a T-cell activator that accelerates fibrosis in this model.  Previous studies have shown that Matrix Metalloproteinase 12 (MMP)-12 is overexpressed in the lungs of patients of sarcoidosis and MMP-12 expression directly correlates with disease severity. The exact role of MMP-12 in the complex inflammatory milieu of sarcoidosis, however, is still unknown.  We hypothesize the MMP-12 plays a role in the initial and late inflammatory responses seen in sarcoidosis and may be associated with development of fibrosis.  

2017 Brody Seed Grant - Project Title : Angle between the Right Ventricular Free Wall and the Inter ventricular Septum at the Apex and anterior Ventricular Insertion Point (VIP) as a marker of Pulmonary Hypertension. 

     PI: Veeranna Maddipati, MD

     Funding Period:  9-1-2017 to 8-31-2018

Introduction: Pulmonary Hypertension (PH) is a progressive and fatal disease which is defined by an elevation of mean pulmonary artery pressure (mPAP) >25 mmHg. Data from the REVEAL registry shows that one in five patients diagnosed with pulmonary arterial hypertension, there was ≥2 years delay between symptom onset and establishing a diagnosis. This is partly because, the high capacitance of the pulmonary circulation compensates for and at least 50% of the pulmonary circulation must be obstructed before a rise in resting pulmonary arterial pressure is detected. The currently available screening test for pulmonary hypertension is echocardiographic estimation of pulmonary artery systolic pressure based on tricuspid regurgitation (TR-Jet) velocity. However, estimation of the TR jet velocity is prone to errors namely under estimating and over estimating the Right Ventricular Systolic pressure. Also, several pre-requisite conditions must be met before a good estimation of the pressure can be made. The ideal screening test for pulmonary hypertension should be able to detect disease even before the tricuspid regurgitation jet can be detected. 

Background: The right ventricular (RV) apex is the point of attachment of the RV free wall to the septum. This portion is heavily trabeculated, not as contractile and will not participate as much in flow exchange. Although it does not contribute to flow exchange, the residual volume of blood may act as padding, preserving kinetic energy and aiding in smooth redirection of the high-velocity inflow blood towards the outflow tract.  Both RV global function parameters and regional strain indices of the apex appeared to detect early signs of ventricular failure. Their use could improve the evaluation of subtle RV changes when TAPSE, tricuspid valve annular systolic velocity, and FAC are not conclusive or in the first stages of PH when TAPSE is known to be still normal. 

This study aims to establish a correlation between the angle of the RV apex, at the Ventricular insertion points and pulmonary hemodynamics as measured by the gold standard method through right heart catheterization.

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Research Curriculum - Fellowship Program


The research curriculum has several components:

  1. Research Projects
  2. Research Rotations
  3. Presentations
  4. Journal Clubs
  5. Lecture Series
  6. Publications
  7. National Meetings


In addition to clinical training, fellows will participate in the division research program and complete a minimum of 6 blocks of research time. There are a wide variety of potential projects ranging from basic science in the Lung Cell Biology Laboratory to clinical studies to epidemiological studies. During the first year the fellow will choose a mentor and begin working on a research program. In addition to longitudinal big picture projects there are a number of different smaller projects that can be accomplished during the time the fellow is on the clinical services.

As a minimum, each fellow is expected to present their work in progress at the monthly research meeting and to prepare and present at least one abstract at a national meeting as well as yearly presentations at the Internal Medicine Research Day. The fellow will be expected to make a presentation at the end of each research block.