Our Studies

The MPMA study is a Phase 2 NIH-funded RCT that aims to improve exercise tolerance in patients with heart failure with preserved ejection fraction (HFpEF). While many studies have focused on improving ‘peak’ aerobic capacity, most daily activities do not reach peak exertion. Rather, patients are often unable to perform the kind of exercise and exertion needed to complete their daily activities of living. Yet exactly why this is the case is unclear. Our group has focused on the skeletal muscle as therapeutic target, with the idea that improving skeletal muscle function and energy production may translate into improved exercise tolerance. The MPMA study tests whether potassium nitrate, an intervention that improves blood flow to the exercising muscle, can improve exercise tolerance, particularly when combined with other supplements (nicotinamide riboside and propionyl-l-carnitine) that may improve the ability of the skeletal muscle to make energy.

Participants take part in a randomized, double-blind crossover trial, meaning each person receives all all treatments over separate 6-week periods. Throughout the study, researchers measure exercise endurance, daily activity levels, and how muscles use oxygen and generate energy. Advanced testing is also used to better understand whether a participant’s limitations are driven more by reduced oxygen delivery or by impaired muscle metabolism.

The three interventions to be tested, in random order, include:

• A therapy aimed at improving muscle oxygen delivery (potassium nitrate, KNO₃)
• A combination therapy designed to improve both oxygen delivery and the muscles’ ability to produce energy (KNO₃ plus nicotinamide riboside and propionyl-l-carnitine)
• A comparison treatment (potassium chloride)

Learn more about the MPMA Study

The SAK study is a Phase 2 NIH-funded RCT designed to better understand and improve exercise capacity in people living with heart failure with preserved ejection fraction (HFpEF). Many individuals with HFpEF experience fatigue and shortness of breath during physical activity, and current treatment options remain limited.

Emerging research suggests that these symptoms may be linked not only to the heart, but also to how skeletal muscles use oxygen and produce energy. In particular, problems with muscle metabolism and blood flow may play a key role in limiting exercise ability.

This study tests whether combining two therapies can improve how the body delivers and uses energy during exercise:

• Empagliflozin (EMPA), a medication that affects energy metabolism
• Potassium nitrate (KNO₃), which may improve blood flow and muscle function

Participants take part in a randomized, double-blind crossover trial, meaning each person receives all study treatments at different times. Over three 6-week periods, participants will receive:

• EMPA alone
• EMPA combined with KNO₃
• A comparison treatment (potassium chloride)

Throughout the study, researchers will measure exercise performance, muscle blood flow, and how the body uses different energy sources during activity. Some participants will also undergo advanced imaging and muscle testing to better understand how these treatments affect muscle function at a biological level.

The goal of the SAK study is to identify new, metabolism-focused treatment strategies that can improve daily functioning and quality of life for people with HFpEF.

Learn more about the SAK Study

The Percutaneous Muscle Biopsy Study is designed to better understand how skeletal muscle contributes to exercise limitations in people with conditions such as heart failure, hypertension, and mitochondrial disorders.

Many individuals with heart failure experience reduced exercise capacity that cannot be fully explained by heart function alone. This has led researchers to focus on the role of skeletal muscle, and particularly how it uses oxygen and produces energy during physical activity.

In this study, participants undergo a percutaneous muscle biopsy, a brief and minimally invasive procedure in which a small sample of muscle is taken from the thigh. This allows researchers to directly examine muscle tissue and gain insights that cannot be obtained through non-invasive testing alone.

The study complements ongoing research using advanced, non-invasive techniques to measure muscle function, oxygen use, and metabolic responses to exercise. By combining these approaches with direct tissue analysis, researchers can better understand the biological factors that contribute to fatigue and reduced endurance.

The ultimate goal of the Muscle Biopsy Study is to build a repository of skeletal muscle samples that will support future research and help identify new targets for improving exercise capacity and quality of life in patients with cardiovascular and metabolic conditions.

Learn more about the Percutaneous Muscle Biopsy Study

PI: Dr. Julio Chirinos

The HeartShare study at the University of Pennsylvania is part of a large, national research effort to better understand heart failure with preserved ejection fraction (HFpEF), a complex condition that affects millions of people and currently has limited treatment options.

HFpEF is not a single disease, but rather a collection of different underlying conditions that can vary from person to person. This diversity has made it difficult to develop effective therapies. The goal of HeartShare is to better define these differences and identify specific subtypes of HFpEF that may respond to targeted treatments.

HeartShare combines information from past studies with new data collected from participants across multiple clinical centers. Participants may take part in a registry, which gathers health information over time, and/or a more detailed “deep phenotyping” study that includes comprehensive testing such as imaging, exercise assessments, and blood or tissue samples.

Using advanced tools, including imaging, digital health data, and molecular (“omics”) analyses, researchers are building a rich dataset to better understand how HFpEF affects different organs and systems in the body.

The ultimate goal of the HeartShare study is to enable more personalized, precision-based treatments by identifying the biological mechanisms driving HFpEF in each individual, paving the way for more effective therapies and improved quality of life.

Learn more about the HeartShare Study

PI: Alex Fanaroff

The MOVE-HF study focuses on improving physical activity in people living with heart failure with preserved ejection fraction (HFpEF), a common and growing condition that often causes shortness of breath and fatigue, making everyday activities more difficult. While regular physical activity can improve quality of life and reduce hospitalizations, many patients are unable to access or sustain traditional programs like cardiac rehabilitation.

This study explores new, more accessible ways to support long-term physical activity. Specifically, we are testing whether “gamification”, using game-like features such as points, levels, and rewards, combined with social motivation can help participants stay more active.

In this randomized controlled trial, participants are assigned to one of three groups:

1. A control group
2. A gamification group with social support from a partner
3. A gamification group featuring friendly competition and a leaderboard

The study begins with a 2-week baseline period to measure participants’ usual activity, followed by a 6-month intervention and a 3-month follow-up. Participants wear a daily activity tracker throughout the study.

By making physical activity more engaging and socially motivating, the MOVE-HF study aims to identify practical, scalable strategies to help individuals with HFpEF improve their health and daily functioning.

Learn more about the MOVE-HF Study

PI: Dr. Kelly Allison

The POWERS is an NIH-funded research study that aims to better understand why some people regain weight after losing it, while others are able to keep it off. This research focuses on adults with obesity and looks at the biological factors that may influence long-term weight maintenance after a structured weight loss program.

Participants begin with a baseline evaluation and then take part in a behavioral weight loss program lasting up to 20 weeks, with the goal of losing at least 7% of their starting body weight within 35 weeks.

Those who achieve this goal are asked to maintain a stable weight for 2 weeks before completing a follow-up clinical assessment. Participants are then tracked for one year to monitor changes over time. During this period, they return for two additional study visits: one about 4 months after completing the program and another at 12 months.

By identifying the physiological differences linked to weight regain, the POWERS study aims to inform more effective, personalized strategies for long-term weight management.

Related Publications:

• The Physiology Of the WEight Reduced State (POWERS) study: design and rationale for assessment of food intake, physical activity and other behavioral constructs
• The Physiology of the WEight-Reduced State (POWERS) study: environmental, psychological, and social determinants of health
• The Physiology Of the WEight Reduced State (POWERS) study: overview and study design
• The Physiology Of the WEight Reduced State (POWERS) study: strategies for the analysis of biological specimens

Learn more about the POWERS Study