Replenishing a vital molecule in stiff heart failure patients and examining effect on heart stiffness, blood pressure, and exercise tolerance

Replenishing cardiac levels of oxidized nicotinamide adenine dinucleotide with precursor nicotinamide riboside in patients with heart failure with preserved ejection fraction, and determination of the effect on cardiac diastolic function, exercise tolerance, blood pressure, and glucose tolerance

Status

Not yet recruiting

Phases

Phase 4

Study type

Interventional

Source

ANZCTR

Registry ID

ACTRN12622000372785

Enrollment

400

Registered

2022-03-03

Start date

2022-04-05

Completion date

2025-04-08

Last updated

2022-03-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

None listed

Brief summary

We recently discovered a deficiency of oxidized nicotinamide adenine dinucleotide in the hearts of patients with stiff heart failure. We have shown that replenishing heart levels of this molecule in a mouse model of stiff heart failure can completely rescue this disease. Now, we will deliver the same precursor of this molecule, as used in mice, to human patients with this disease, for three months. At the end of the three months, we will determine if they have had any benefits in heart stiffness, exercise tolerance, blood pressure, and glucose tolerance.

Interventions

Determining if oral supplementation with nicotinamide riboside (precursor of NAD+) for 3 months can improve left ventricular diastolic function. Supplement Details: Generic name: Nicotinamide riboside (NR). Supplier: Chromadex. Dose administered: 1g twice/day of NR. Duration of administration: one month. Mode of administration: oral capsule. Compliance: drug tablet return, verbal confirmation

Study design

Allocation

Randomised controlled trial

Intervention model

Parallel

Primary purpose

Treatment

Masking

Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

All

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

1. All members of the specialist HFpEF clinic at RPAH who consent. In order to be a member of the HFpEF clinic, patients have met the following criteria at the time of clinic admission: a. Recent hospital admission (within the previous 12 months) with heart failure b. Left ventricular ejection fraction greater than or equal to 45% on echocardiogram within the previous 6 months 2. Concomitant diseases: all patients who consent, regardless of concomitant disease. Except for end-stage renal disease (CKD greater than or equal to stage 4), liver failure (hepatic encephalopathy with impaired synthetic function as determined by INR greater than or equal to 1.5 in the absence of anticoagulant therapy) or malignant cancer. 3. Willingness to provide informed consent and willingness to participate. 4. Agreement of the treating cardiologist.

Exclusion criteria

1. Participants with end-stage kidney (CKD greater than or equal to stage 4) or liver failure (hepatic encephalopathy with impaired synthetic function as determined by INR equal to or greater than 1.5 in the absence of anticoagulant therapy). 2. Participants with a history of a psychological illness or other conditions that may interfere with their ability to understand the study requirements. 3. Patients already taking NAD+ precursors including niacin, nicotinamide, or nicotinamide riboside.

Outcome results