NAD+ and Exercise in FA

NCT04192136 | Completed Results DMC

• 2 other identifiers: 19-016634R01HL149722
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

Randomized, placebo-controlled trial with a 2x2 factorial design testing the effects of an NAD+ precursor (NR) and exercise on Peak VO2 and Si in Friedreich's Ataxia (FA). The primary objective of this research is to measure the effect of combination administration (NR + exercise) on aerobic capacity (Peak VO2) in FA. A key secondary objective is to measure the effect of combination administration (NR + exercise) on glucose homeostasis (Si) in FA.

Conditions

Friedreich Ataxia 1

Outcome Measures

Primary Outcomes (1)

• Within-Participant Change in Peak V02 (Maximal Oxygen Uptake on Cardiopulmonary Exercise Testing)

  Peak V02 will be assessed by completion of an incremental symptom-limited cardio-pulmonary Exercise Stress Test (EST) on a recumbent leg cycle ergometer. The index is based on the change in peak V02 given in liters per minute (L/min), and a higher value indicates greater oxygen uptake.

  Baseline to 12 Weeks

Secondary Outcomes (1)

• Within-Participant Change in Whole Body Insulin Sensitivity (Si)

  Baseline to 12 Weeks

Study Arms (4)

Nicotinamide Riboside (NR)

EXPERIMENTAL

Investigators will use Good Manufacturing Process (GMP)-grade 300 mg capsules of the dietary supplement nicotinamide riboside (ChromaDex, Irvine CA). Investigators dose based on body weight, and monitor for adverse effects (AEs). For individuals with weight \> 72 kg: 900 mg po qd x 12 wks. For individuals with weight \> 48 kg and ≤ 72 kg: 600 mg po qd x 12 wks. For individuals with weight 24 ≤ 48 kg: 300 mg po qd x 12 wks.

Dietary Supplement: Nicotinamide Riboside

Placebo

PLACEBO COMPARATOR

Matched placebo will contain the same excipients without the active supplement and is generally recognized as safe. The placebo will be covered in an identical capsule (NR will be covered in the same capsule). Doses of placebo will match the body weight schema for dosing of NR. Investigators dose based on body weight, and monitor for adverse effects (AEs). For individuals with weight \> 72 kg: 900 mg po qd x 12 wks. For individuals with weight \> 48 kg and ≤ 72 kg: 600 mg po qd x 12 wks. For individuals with weight 24 ≤ 48 kg: 300 mg po qd x 12 wks.

Dietary Supplement: Placebo

Exercise Intervention and NR

EXPERIMENTAL

The exercise program consists of at-home training sessions: 3 aerobic sessions per week on the in-home bike trainer, and 2 resistance exercise sessions per week using resistance bands. All sessions will begin with stretching and brief aerobic warm-up exercise on the in-home bike trainer. On resistance training days, subjects will be given instructions to complete circuits of resistance exercises. Participants in this arm will receive both the Exercise Intervention and the NR.

Dietary Supplement: Nicotinamide Riboside; Other: Exercise Intervention

Exercise Intervention and Placebo

EXPERIMENTAL

The exercise program consists of at-home training sessions: 3 aerobic sessions per week on the in-home bike trainer, and 2 resistance exercise sessions per week using resistance bands. All sessions will begin with stretching and brief aerobic warm-up exercise on the in-home bike trainer. On resistance training days, subjects will be given instructions to complete circuits of resistance exercises. Participants in this arm will receive both the Exercise Intervention and the Placebo.

Dietary Supplement: Placebo; Other: Exercise Intervention

Interventions

Nicotinamide Riboside DIETARY_SUPPLEMENT

Investigators will use (Good Manufacturing Process) GMP-grade 300 mg capsules of the dietary supplement nicotinamide riboside (ChromaDex, Irvine CA). NR is distributed by ChromaDex, Inc., Irvine, CA. NR is available as 300 mg capsules. The dietary supplement will be re-labeled by the Hospital of the University of Pennsylvania (HUP) Investigational Drug Service according to FDA regulations, including subject and physician name and NR or Placebo 300 mg capsules.

Exercise Intervention and NR; Nicotinamide Riboside (NR)

Placebo DIETARY_SUPPLEMENT

The matched placebo will contain the same excipients without the active supplement and is generally recognized as safe. The placebo will be covered in an identical capsule (NR will be covered in the same capsule).

Exercise Intervention and Placebo; Placebo

Exercise Intervention OTHER

The exercise program consists of at-home training sessions: 3 aerobic sessions per week on the in-home bike trainer, and 2 resistance exercise sessions per week using resistance bands. On aerobic training days, subjects will be given instruction on a recumbent Catrike trainer, titrated such that they spend 20 minutes at their target heart rate as determined by baseline Exercise Stress Test (EST) (60-80% of their heart rate at peak VO2) and as measured by their wearable device. On resistance training days, subjects will be given instructions to complete circuits of resistance exercises. Resistance training intensity (as determined by graded resistance bands) will be maintained at 60% of pre-training maximal voluntary contraction for each muscle group.

Exercise Intervention and NR; Exercise Intervention and Placebo

Eligibility Criteria

• Age: 10 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Molecular diagnosis of Friedrich's Ataxia (FA).
• Males and Females, Age 10 to 40 years (inclusive).
• Girls, 11 years of age and older, must have a negative urine/serum pregnancy test and must use an acceptable method of contraception, including abstinence, a barrier method (diaphragm or condom), Depo-Provera, or an oral contraceptive, for the duration of the study.
• Not currently meeting exercise guidelines as outlined by The Physical Activity Guidelines for Americans.
• Children and Adolescents should do 60 minutes (1 hour) or more of moderate-to-vigorous physical activity daily.
• As a part of their physical activity, children and adolescents should include muscle-strengthening physical activity on at least 3 days a week.
• Adults should do at least 150 minutes (2 hours and 30 minutes) to 300 minutes (5 hours) a week of moderate-intensity, or 75 minutes (1 hour and 15 minutes) to 150 minutes (2 hours and 30 minutes) a week of vigorous-intensity aerobic physical activity.
• Adults should also do muscle-strengthening activities of moderate or greater intensity that involve all major muscle groups on 2 or more days a week.
• Cardiac echocardiogram or cardiac MRI, performed within 1 year of enrollment, showing an LVEF \> 45%
• ECG, performed within 1 year of enrollment, without clinically significant arrhythmia.
• Weight \> 24 kg
• Parental/guardian permission (informed consent) and if appropriate, child assent.

You may not qualify if:

• Known sensitivity to NR.
• Concurrent use of any medications, including statins, likely to increase risk of NR toxicity.
• HgbA1c \> 8.5% and/or Diabetes Mellitus (DM) requiring insulin or insulin secretagogue.
• Use of supraphysiologic steroids.
• Laboratory abnormalities that indicate clinically significant anemia or bleeding risk. (Hemoglobin \< 10 g/dL or Platelets \< 100K)
• Laboratory abnormalities that indicate clinically significant kidney disease using serum creatinine and Modification of Diet in Renal Disease (MDRD) equation. (Estimated Glomerular Filtration Rate (eGFR) \< 60 ml/min/1.73 m2)
• Laboratory abnormalities that indicate clinically significant liver disease. (Aspartate Aminotransferase (AST)/Serum Glutamic Oxaloacetic Transaminase (SGOT) 3.0 x Upper Limit of Normal and/or Alanine Aminotransferase (ALT)/Serum Glutamic Pyruvic Transaminase (SGPT) 3.0 x Upper Limit of Normal)
• Uncontrolled and persistent arrhythmias that are felt to be clinically significant.
• Known history of moderate or severe left ventricular systolic dysfunction (Left Ventricular Ejection Fraction (LVEF) \< 45%)
• Standard contraindications to exercise testing.
• Inability to sit and pedal unassisted in a cycle ergometry chair, at a cadence of at least 55 rotations per minute (rpm) during unloaded warm up, in a cycle ergometry chair and complete a maximal Cardio Pulmonary Exercise Test (CPET)
• Inability to sit and pedal unassisted in a recumbent tricycle.
• Any contraindication to MRI. Including:
• Any intra-luminal implant, filter, stent or valve replacement
• Any type of life assist device, pump, or prosthetic

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Friedreich Ataxia 1

Interventions

nicotinamide-beta-riboside

Results Point of Contact

• Title: Shana McCormack, MD
• Organization: Children's Hospital of Philadelphia

mccormacks1@chop.edu

617-596-9067

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The participants and the investigator team will be blinded as to the group assignment: NR vs Placebo. All collected data (e.g., questionnaires) will be coded, so initial analysis will be conducted without knowledge of the participant's group status. While the assignment of participants to the exercise groups will not be blinded to the participant or majority of the study team, a designated blinded technician will perform the follow-up Cardio Pulmonary Exercise Testing. Follow-Up Cardio Pulmonary Exercise Testing will be performed by a dedicated blinded study team member, an exercise technician, who will not know if the participant was assigned to an arm including the exercise intervention.
• Purpose: OTHER
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, placebo-controlled trial with a 2x2 factorial design testing the effects of an NAD+ precursor (NR) and exercise.

Study Record Dates

• First Submitted: December 6, 2019
• First Posted: December 10, 2019
• Study Start: September 3, 2020
• Primary Completion: February 7, 2025
• Study Completion: October 31, 2025
• Last Updated: March 11, 2026
• Results First Posted: March 11, 2026

Record last verified: 2026-03

Locations

US (1)