R01HL159997

Physical Activity in Pulmonary Arterial Hypertension (ACTIPH) - Pulmonary Arterial Hypertension (PAH) is characterized by limitation of physical activity even with current effective treatments.

Most observational studies, clinical trials, and outpatient clinical assessments of patients with PAH focus on exercise capacity (the maximal effort a person can achieve under controlled circumstances), measured by cardiopulmonary exercise or six-minute walk testing. However, these artificial tests do not capture the intensity, frequency, duration, context, and pattern of physical activity throughout the day or week in the patient's life.

Such an activity "signature" or phenotype may more accurately reflect an individual's function and perceived health-related quality of life (HRQOL) by providing insight into multisystem function, side effects, and treatment benefits and burdens. A physical activity intervention which is personalized for a PAH patient could lead to improvements in psychosocial function, symptoms, HRQOL, fitness, and even survival.

Unfortunately, there have been very few published studies of physical activity in PAH patients, none of which have assessed multidimensionality in a large multicenter cohort. We have performed preliminary studies using traditional accelerometry which have shown that patients with PAH cluster into low, medium, and high activity phenotypes which show differences in six-minute walk distance and HRQOL. Functional principal components analysis has identified "signatures" of physical activity patterns throughout the day in PAH.

Novel biosensors which continuously capture multiple streams of data in real time (including accelerometry) would provide an innovative approach to remote clinical monitoring and may increase the efficiency and pertinence of clinical trials in PAH.

The Pulmonary Hypertension Association Registry (PHAR) has been prospectively collecting data from adult and pediatric PAH patients from centers throughout the United States since 2015. The PHAR has enrolled 1400 patients with 2000 patient-years of follow-up at 52 centers, representing one of the largest multicenter registries of patients with PAH.

We propose to measure accelerometry for one-week periods biannually for >1400 patients over four years (~7000 assessments) in the PHAR with high efficiency and low patient burden. We aim to determine the predictors of physical activity phenotype and whether physical activity patterns are associated with health-related quality of life, emergency department visits, hospitalizations, and time to lung transplantation or death in PAH. We will estimate the "minimally important difference" in physical activity which could be used as an endpoint in clinical trials in PAH. We will incorporate a novel wearable biosensor which could be used to advance these models of physical activity in PAH.

Trustees Of The University Of Pennsylvania

THE DIVISION OF LUNG DISEASES SUPPORTS RESEARCH AND RESEARCH TRAINING ON THE CAUSES, DIAGNOSIS, PREVENTION, AND TREATMENT OF LUNG DISEASES AND SLEEP DISORDERS. RESEARCH IS FUNDED THROUGH INVESTIGATOR-INITIATED AND INSTITUTE-INITIATED GRANT PROGRAMS AND THROUGH CONTRACT PROGRAMS IN AREAS INCLUDING ASTHMA, BRONCHOPULMONARY DYSPLASIA, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, CYSTIC FIBROSIS, RESPIRATORY NEUROBIOLOGY, SLEEP AND CIRCADIAN BIOLOGY, SLEEP-DISORDERED BREATHING, CRITICAL CARE AND ACUTE LUNG INJURY, DEVELOPMENTAL BIOLOGY AND PEDIATRIC PULMONARY DISEASES, IMMUNOLOGIC AND FIBROTIC PULMONARY DISEASE, RARE LUNG DISORDERS, PULMONARY VASCULAR DISEASE, AND PULMONARY COMPLICATIONS OF AIDS AND TUBERCULOSIS. THE DIVISION IS RESPONSIBLE FOR MONITORING THE LATEST RESEARCH DEVELOPMENTS IN THE EXTRAMURAL SCIENTIFIC COMMUNITY AS WELL AS IDENTIFYING RESEARCH GAPS AND NEEDS, OBTAINING ADVICE FROM EXPERTS IN THE FIELD, AND IMPLEMENTING PROGRAMS TO ADDRESS NEW OPPORTUNITIES. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, USE SMALL BUSINESS TO MEET FEDERAL RESEARCH AND DEVELOPMENT NEEDS, FOSTER AND ENCOURAGE PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY SOCIALLY AND ECONOMICALLY DISADVANTAGED PERSONS, AND INCREASE PRIVATE-SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, FOSTER TECHNOLOGY TRANSFER THROUGH COOPERATIVE R&D BETWEEN SMALL BUSINESSES AND RESEARCH INSTITUTIONS, AND INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL R&D.

93.837 - Cardiovascular Diseases Research

National Heart Lung and Blood Institute (NHLBI) [HHS - NIH]

Philadelphia, Pennsylvania 191044865 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 395% from $1,123,529 to $5,556,139.