Nicotinamide Riboside Supplementation in Chronic Kidney Disease

Official title

Pilot Randomized Crossover Trial of Nicotinamide Riboside in Chronic Kidney Disease (NR-CKD Trial)

Overview

This study is testing whether a dietary supplement called nicotinamide riboside, (NR), can be used in adults with moderate chronic kidney disease. NR is a form of vitamin B3 that may help support cellular energy metabolism. The main goal of this study is to see whether it is feasible for people with chronic kidney disease to take NR daily, complete study visits, and follow the study procedures. The study will also explore whether NR chloride affects markers of mitochondrial health, small blood vessel function, and physical function. Participants will be randomly assigned to one of two treatment orders. One group will take NR first and placebo second. The other group will take placebo first and NR second. Placebo looks like NR but does not contain active NR. Each treatment period lasts 12 weeks, with an approximately 2-week washout period between treatments. Neither participants nor the study team will know which treatment participants are taking during each period. Study visits will include blood and urine collection, physical function testing, and noninvasive tests of small blood vessel function. The study will enroll up to 36 adults with moderate chronic kidney disease at the University of California, San Diego.

Detailed description

Chronic kidney disease is associated with impaired mitochondrial function, vascular dysfunction, reduced physical function, and increased risk of cardiovascular and functional decline. Nicotinamide riboside is a vitamin B3 derivative and NAD+ precursor that may support cellular energy metabolism and vascular health.

This pilot study will evaluate the feasibility of using nicotinamide riboside in adults with moderate chronic kidney disease. The study uses a randomized, double-blind, placebo-controlled crossover design so that each participant receives both nicotinamide riboside chloride and placebo during separate treatment periods.

In addition to feasibility measures, the study will collect exploratory data on mitochondrial, microvascular, and physical function outcomes. These data will help determine whether a larger clinical trial of nicotinamide riboside in chronic kidney disease is practical and scientifically justified.

Interventions

• Dietary supplement Nicotinamide Riboside (NR)
  Nicotinamide riboside will be administered orally at a target dose of 1000 mg/day for 12 weeks during the active treatment period.
• Dietary supplement Matched Placebo (Capsules)
  Matched placebo will be administered orally for 12 weeks during the placebo treatment period. The placebo will be identical or substantially similar in appearance to the active nicotinamide riboside study product to maintain blinding.

Primary outcome measures

• Change in plasma cell-free mitochondrial DNA [Time frame: Baseline, Week 12, and Week 26]
• Change in urine cell-free mitochondrial DNA [Time frame: Baseline, Week 12, and Week 26]

Secondary outcome measures (6)

• Change in skin fingernail capillary density [Time frame: Baseline, Week 12, and Week 26]
• Change in skin blood flow [Time frame: Baseline, Week 12, and Week 26]
• Change in six-minute walk distance [Time frame: Baseline, Week 12, and Week 26]
• Change in Handgrip Strength [Time frame: Baseline, Week 12, and Week 26]
• Change in Timed Up and Go [Time frame: Baseline, Week 12, and Week 26]
• Change in 30-second sit-to-stand [Time frame: Baseline, Week 12, and Week 26]

Eligibility criteria

Inclusion criteria

• Moderate chronic kidney disease not treated with dialysis, defined as eGFR 30-59 mL/min/1.73 m2 using the CKD-EPI equation.
• Urine albumin-to-creatinine ratio (uACR) <300 mg/g.
• Able to provide informed consent.
• Able to walk unassisted from room to room, with usual assistive device allowed if approved by study safety assessment.
• Willing and able to comply with study procedures, visits, and study product administration.

Exclusion criteria

• Pregnancy.
• Expectation to start dialysis within 6 months.
• Unable to walk unassisted from room to room.
• Institutionalization or inability to consent.
• End-stage liver disease with cirrhosis.
• HIV.
• Oxygen-dependent COPD.
• Baseline systolic blood pressure >170 mmHg or diastolic blood pressure >100 mmHg.
• Current participation in another interventional trial.
• Use of immunosuppressive medications, including steroids or calcineurin inhibitors.
• Malignancy requiring active treatment or currently under surveillance at the discretion of the investigator.
• Hospitalization for myocardial infarction, unstable angina, cerebrovascular accident, or unstable cardiac chest pain within the prior 3 months.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Triple blind

Primary purpose

Treatment

Study locations

United States · 1 center

• Altman Clinical and Translation Research Institute — San Diego

Publications

• Trammell SA, Schmidt MS, Weidemann BJ, Redpath P, Jaksch F, Dellinger RW, Li Z, Abel ED, Migaud ME, Brenner C. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nat Commun. 2016 Oct 10;7:12948. doi: 10.1038/ncomms12948. PMID 27721479
• Martens CR, Denman BA, Mazzo MR, Armstrong ML, Reisdorph N, McQueen MB, Chonchol M, Seals DR. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat Commun. 2018 Mar 29;9(1):1286. doi: 10.1038/s41467-018-03421-7. PMID 29599478
• Conze D, Brenner C, Kruger CL. Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults. Sci Rep. 2019 Jul 5;9(1):9772. doi: 10.1038/s41598-019-46120-z. PMID 31278280

Identifiers

NCT: NCT07693543 · UCSD-NR-001 · 1K01DK147652

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗