Clinical Trials Logo

Clinical Trial Summary

Background:

People are living longer and are more likely to survive a heart attack if they have one. Longer life expectancy is good but it also means more people get chronic heart failure over time. This is a condition in which the heart doesn't pump blood as well as it should. Treatment of chronic heart failure has not improved much in a few decades. Researchers want to see if giving a dietary supplement to people with heart failure can help their heart function. The supplement is nicotinamide riboside (NR).

Objective:

To study how NR affects skeletal muscle function in people with heart failure.

Eligibility:

Adults ages 18-70 with clinically stable systolic heart failure

Design:

Participants will be screened with a medical history and physical exam. They will answer demographic questions and review their current medical treatments. They will have blood and urine tests. They will have an echocardiogram. This uses sound waves to test heart function.

Participants will have 8 study visits over 16 weeks. At these visits, they will have some of the following:

Repeat of screening tests

Skin sample taken

Skeletal muscle exercise NMR spectroscopy. Muscles will be measured while participants do foot exercises.

Cardiopulmonary exercise testing. Participants may ride a stationary bike or walk on a treadmill. A facemask will analyze their breath. Heart and blood pressure measurements will be taken.

Participants will take the supplement in pill form each day for 12 weeks. Pill bottles will be checked at study visits.

Participants should not significantly change their activity levels during the study.


Clinical Trial Description

As life expectancy increases and acute cardiac mortality decreases, the incidence of chronic heart failure (HF) continues to rise, and despite this, conceptual advances in the treatment of chronic heart failure have not increased substantially over last few decades. One intracellular component of heart failure progression is mitochondrial bioenergetic dysfunction. Although the mechanism underpinning this is not completely understood, recent metabolomics data demonstrated an incomplete flux of metabolites through oxidative phosphorylation (OX PHOS) in HF. In parallel, data has shown that hyperacetylation of mitochondrial bioenergetic enzymes, with the concomitant blunting of enzymatic activity is evident in HF. Putting these together, an emerging hypothesis implicates excessive acetylation of mitochondrial proteins with the subsequent blunting of bioenergetic enzyme function, as a mechanism underpinning incomplete flux through OX PHOS resulting in HF progression.

In parallel with cardiac bioenergetic deficiency chronic HF subjects display disrupted skeletal muscle OX PHOS, which is thought to contribute towards overall fatigue and reduced exercise tolerance. Interestingly exercise training in HF subjects improves skeletal muscle mitochondrial OX PHOS capacity and subject activity levels. Exercise training additionally increases activity of the mitochondrial regulatory deacetylase sirtuin enzymes SIRT1 and SIRT3, in parallel with improved skeletal muscle OX PHOS capacity. At the same time HF-associated disruption in skeletal muscle metabolic function activates skeletal muscle cytokine production. These inflammatory programs, in turn, are proposed to contribute towards impaired functional capacity in HF. Interestingly, and mirroring improved OX PHOS following exercise programs in HF studies, exercise training similarly reduces skeletal muscle inflammatory effects.

Biochemical and bioenergetic consequences of impaired mitochondrial OX PHOS leads to decreased NAD+ levels, which exacerbate mitochondrial dysfunction by inactivating the NAD+ dependent sirtuin enzymes. Experimental studies using NAD+ precursors to increase NAD+ production have been shown to normalize NADH/NAD+ ratios and activate Sirtuin enzymes, resulting in enhanced OX PHOS with beneficial effects in numerous systems including skeletal muscle and in the blunting of inflammation.

In this pilot study we will directly assess the effect of the NAD+ precursor, nicotinamide riboside (NR) on skeletal muscle mitochondrial OX PHOS in HF subjects using: skeletal muscle NMR spectroscopy assessment of the rate of high energy phosphate recovery in response to submaximal exercise; assessment of the effect of NR on functional capacity using cardiopulmonary exercise testing (CPET) to determine VO(2max) and anaerobic threshold; evaluation of the NR effect on serum metabolomics at rest and in response to CPET; and by measuring circulating cytokine levels pre- and post- NR administration. These studies would enable a more comprehensive assessment of the role for NR supplementation on skeletal muscle mitochondrial function in subjects with systolic HF ;


Study Design


Related Conditions & MeSH terms


NCT number NCT03565328
Study type Interventional
Source National Institutes of Health Clinical Center (CC)
Contact Autumn Mains, R.N.
Phone (410) 627-3494
Email autumn.mains.ctr@usuhs.edu
Status Recruiting
Phase Phase 2
Start date September 27, 2018
Completion date June 1, 2022

See also
  Status Clinical Trial Phase
Recruiting NCT03615469 - Building Strength Through Rehabilitation for Heart Failure Patients (BISTRO-STUDY) N/A
Active, not recruiting NCT03549169 - Decision Making for the Management the Symptoms in Adults of Heart Failure N/A
Withdrawn NCT03091998 - Subcu Administration of CD-NP in Heart Failure Patients With Left Ventricular Assist Device Support Phase 1
Recruiting NCT03300791 - Predictive Models of Readmission in Heart Failure N/A
Completed NCT03294512 - Pilot and Feasibility Study of a MAWDS (Medications, Activity, Weight, Diet and Symptoms) Heart Failure Mobile Platform N/A
Recruiting NCT03560167 - Early Feasibility Study of the AccuCinch® Ventricular Repair System in Patients With Prior Mitral Valve Intervention (PMVI) and Recurrent Mitral Regurgitation - The CorCinch-PMVI Study N/A
Active, not recruiting NCT03281122 - A Study of BMS-986224 in Healthy Subjects and Heart Failure Patients With Reduced Ejection Fraction Phase 1
Recruiting NCT02275819 - Exercise Training in Heart Failure: Changes in Cardiac Structure and Function
Completed NCT03238729 - Proof-of-Concept Study of Heart Habits Application for Patients With Heart Failure N/A
Not yet recruiting NCT02784912 - Biomarkers in Risk Stratification of Sustainted Ventricular Tachycardia or Electrical Storm After Ablation N/A
Recruiting NCT02877914 - China PEACE 5r-HF Study N/A
Recruiting NCT02674438 - Comparison of Outcomes and Access to Care for Heart Failure Trial Phase 3
Recruiting NCT02823795 - The Supporting Patient Activation in Transition to Home Intervention N/A
Recruiting NCT02713126 - Inorganic Nitrite to Amplify the Benefits and Tolerability of Exercise Training in Heart Failure With Preserved Ejection Fraction (HFpEF) (INABLE-Training) Phase 2
Recruiting NCT03013270 - Aerobic, Resistance, Inspiratory Training Outcomes in Heart Failure N/A
Recruiting NCT02922478 - Role of Comorbidities in Chronic Heart Failure Study
Active, not recruiting NCT02911493 - Reducing Sedentary Time in Patients With Heart Failure N/A
Not yet recruiting NCT02821065 - Telehealth for Emergency-Community Continuity of Care Connectivity Via Home-Telemonitoring N/A
Completed NCT02921607 - Development of Scalable New Model(s) Focused on Care Co-ordination and Care Provision for Medically Complex, Co-morbid Chronic Disease Patient Segments Focusing on Heart Failure
Withdrawn NCT02624960 - Safety and Performance of the AccuCinch® System N/A