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| ID | Type | Description | Link |
|---|---|---|---|
| R01HL149722 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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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.
Friedreich's Ataxia (FA) is a progressive neurodegenerative disease affecting 1 in 50,000 individuals in the U.S. Currently, there is no approved treatment.
There is a critical knowledge gap regarding the best ways to intervene to increase aerobic capacity (Peak VO2 on exercise testing) in FA. Exercise is the most potent known stimulus for increasing muscle mass and mitochondrial oxidative phosphorylation (OXPHOS) capacity, increasing Peak VO2, and increasing insulin sensitivity (Si), however, it has not been studied in FA. One adaptation seen in exercised muscles is an increase in muscle nicotinamide adenine dinucleotide (NAD+), a cofactor required for glycolytic and mitochondrial adenosine triphosphate (ATP) production. In skeletal- and cardiac muscle-specific frataxin (FXN) knock-out animals, NAD+ precursors rescued cardiac function to near-normal, additionally highlighting its translational potential in FA. Nicotinamide riboside (NR) is a NAD+ precursor currently available as a dietary supplement (Tru Niagen ®, ChromaDex, Irvine CA) that is expected to be safe and well-tolerated in adults and children. The central hypothesis is that exercise + NR will increase skeletal muscle mitochondrial OXPHOS and increase muscle mass to increase Peak VO2 in FA. The investigators expect that exercise + NR will also increase Si in this cohort.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Within-Participant Change in Whole Body Insulin Sensitivity (Si) | Whole Body Insulin Sensitivity (Si) will be assessed by completion of a stable isotope tracer-enhanced Oral Glucose Tolerance Test (OGTT). Samples will be collected at 10 time points for analysis. The unit of measure is based on the change insulin values given in microunits per milliliter (μU/mL) and those of glucose, in milligrams per deciliter, and a higher value indicates greater insulin sensitivity. The whole body insulin sensitivity index (WBISI), also known as the Matsuda index or composite ISI, is dimensionless (unitless). |
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Inclusion Criteria:
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.
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.
Exclusion Criteria:
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
Any vascular clip or clamp
Any surgically placed clips or clamps or bands on visceral organs
Any intracranial implants of any type other than dental fillings
Any non-removable piercings, jewelry, or medicinal patch
Any personal history of intraocular injury or fragment in or around the orbit that cannot be cleared through radiologic examination.
Any personal history of bullet, shrapnel, or stabbing wounds that cannot be cleared through radiologic evaluation.
Inability to lie flat in the MRI scanner for 60-90 minutes.
Use of any investigational agent within 4 weeks of enrollment, except open-label extension phase.
Females: pregnant, lactating, or planning to become pregnant during their participation.
Any medical condition, in the opinion of the investigator that will interfere with the safe completion of the study.
Parents/guardians or participants who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 42009009 | Derived | Lin KY, Bucha A, McSweeney K, Wade KL, Karaj A, Tamaroff J, O'Malley S, Chung NM, Cilenti NA, Wanner J, Adzika GK, Mesaros C, Blair IA, Rojsajjakul T, Serai S, Farmer J, Bryant K, Lu Y, Harhay MO, Weber DR, Paridon SM, Seifert EL, Putt ME, Zamani P, Baur JA, Lynch DR, McCormack SE. Safety and efficacy of individualised exercise and NAD+ precursor supplementation in patients with Friedreich's ataxia in the USA: a single-centre, 2 x 2 factorial, randomised controlled trial. Lancet Neurol. 2026 May;25(5):469-481. doi: 10.1016/S1474-4422(26)00082-7. |
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Once consent was obtained, participants were reviewed for eligibility and inclusion in the trial. Individuals meeting criteria were randomized. In total, 75 participants signed informed consent. There was 1 withdrawal of consent prior to in-person screening (ankle injury). 74 completed in-person screening. 8 were considered ineligible after screening due to: not reaching cadence during CPET (7) and not able to complete blood draw (1)
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| ID | Title | Description |
|---|---|---|
| FG000 | Nicotinamide Riboside (NR) | 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. Nicotinamide Riboside: 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. |
| FG001 | Placebo | 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. Placebo: 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). |
| FG002 | Exercise Intervention and NR | 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 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. Nicotinamide Riboside: Investigators will use (Good Manufacturing Process) GMP-grade 300 mg capsules of the dietary supplement nicotinamide riboside, distributed by ChromaDex, Inc., Irvine, CA. 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: On aerobic 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 days, subjects will be instructed to complete circuits of resistance exercises. Training intensity (as determined by graded resistance bands) will be maintained at 60% of pre-training maximal voluntary contraction for each muscle group. |
| FG003 | Exercise Intervention and Placebo | 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 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. Nicotinamide Riboside: Investigators will use (Good Manufacturing Process) GMP-grade 300 mg capsules of the dietary supplement nicotinamide riboside, distributed by ChromaDex, Inc., Irvine, CA. 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: On aerobic 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 days, subjects will be instructed to complete circuits of resistance exercises. Training intensity (as determined by graded resistance bands) will be maintained at 60% of pre-training maximal voluntary contraction for each muscle group. |
| FG004 | Patients Not Randomized | Patients who signed consent but did not meet eligibility for the study, and did not proceed to randomization |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Data not collected for non-randomized participants
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| ID | Title | Description |
|---|---|---|
| BG000 | Nicotinamide Riboside (NR) | 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. Nicotinamide Riboside: 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | One individual in the Placebo group did not attempt a CPET at week 12 because of an intercurrent foot injury, and thus did not contribute to the analysis for the main outcome | Posted | Median | Inter-Quartile Range | L/min | Baseline to 12 Weeks |
|
Adverse Event data were collected from the time of informed consent through the duration of participation (Up to 24 Weeks).
Adverse events (AEs) were tracked systematically. Only Grade 1 and Grade 2 AEs occurred.
Non-randomized participants were not assessed for deaths or adverse events
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Nicotinamide Riboside (NR) | 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. Nicotinamide Riboside: 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| GI Disorders | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment | Constipation, Diarrhea, Dysphagia, GERD, Nausea, Stomach Pain, Vomiting, Other |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Shana McCormack, MD | Children's Hospital of Philadelphia | 617-596-9067 | mccormacks1@chop.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 19, 2024 | Nov 7, 2025 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 2, 2025 | Dec 2, 2025 | SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jun 5, 2024 | Nov 7, 2025 | ICF_002.pdf |
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| ID | Term |
|---|---|
| C565561 | Friedreich Ataxia 1 |
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| ID | Term |
|---|---|
| C018613 | nicotinamide-beta-riboside |
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Randomized, placebo-controlled trial with a 2x2 factorial design testing the effects of an NAD+ precursor (NR) and exercise.
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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.
| 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. |
|
|
| 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 | 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. |
|
| Baseline to 12 Weeks |
| could not reach required cadence during CPET at Baseline Visit |
|
| not able to complete blood draw at Baseline visit |
|
| BG001 | Placebo | 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. Placebo: 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). |
| BG002 | Exercise Intervention and NR | 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 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. Nicotinamide Riboside: Investigators will use (Good Manufacturing Process) GMP-grade 300 mg capsules of the dietary supplement nicotinamide riboside, distributed by ChromaDex, Inc., Irvine, CA. 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: On aerobic 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 days, subjects will be instructed to complete circuits of resistance exercises. Training intensity (as determined by graded resistance bands) will be maintained at 60% of pre-training maximal voluntary contraction for each muscle group. |
| BG003 | Exercise Intervention and Placebo | 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 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. Nicotinamide Riboside: Investigators will use (Good Manufacturing Process) GMP-grade 300 mg capsules of the dietary supplement nicotinamide riboside, distributed by ChromaDex, Inc., Irvine, CA. 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: On aerobic 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 days, subjects will be instructed to complete circuits of resistance exercises. Training intensity (as determined by graded resistance bands) will be maintained at 60% of pre-training maximal voluntary contraction for each muscle group. |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Placebo | 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. Placebo: 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). |
| OG002 | Exercise Intervention and NR | 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 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. Nicotinamide Riboside: Investigators will use (Good Manufacturing Process) GMP-grade 300 mg capsules of the dietary supplement nicotinamide riboside, distributed by ChromaDex, Inc., Irvine, CA. 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: On aerobic 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 days, subjects will be instructed to complete circuits of resistance exercises. Training intensity (as determined by graded resistance bands) will be maintained at 60% of pre-training maximal voluntary contraction for each muscle group. |
| OG003 | Exercise Intervention and Placebo | 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 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. Nicotinamide Riboside: Investigators will use (Good Manufacturing Process) GMP-grade 300 mg capsules of the dietary supplement nicotinamide riboside, distributed by ChromaDex, Inc., Irvine, CA. 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: On aerobic 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 days, subjects will be instructed to complete circuits of resistance exercises. Training intensity (as determined by graded resistance bands) will be maintained at 60% of pre-training maximal voluntary contraction for each muscle group. |
|
|
| Secondary | Within-Participant Change in Whole Body Insulin Sensitivity (Si) | Whole Body Insulin Sensitivity (Si) will be assessed by completion of a stable isotope tracer-enhanced Oral Glucose Tolerance Test (OGTT). Samples will be collected at 10 time points for analysis. The unit of measure is based on the change insulin values given in microunits per milliliter (μU/mL) and those of glucose, in milligrams per deciliter, and a higher value indicates greater insulin sensitivity. The whole body insulin sensitivity index (WBISI), also known as the Matsuda index or composite ISI, is dimensionless (unitless). | Two individuals each had one result missing due to not completing the full OGTT testing, and thus did not contribute to the analysis for the secondary outcome | Posted | Median | Inter-Quartile Range | Unitless Index Value | Baseline to 12 Weeks |
|
|
|
| 0 |
| 17 |
| 0 |
| 17 |
| 17 |
| 17 |
| EG001 | Placebo | 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. Placebo: 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). | 0 | 17 | 0 | 17 | 17 | 17 |
| EG002 | Exercise Intervention and NR | 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 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. Nicotinamide Riboside: Investigators will use (Good Manufacturing Process) GMP-grade 300 mg capsules of the dietary supplement nicotinamide riboside, distributed by ChromaDex, Inc., Irvine, CA. 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: On aerobic 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 days, subjects will be instructed to complete circuits of resistance exercises. Training intensity (as determined by graded resistance bands) will be maintained at 60% of pre-training maximal voluntary contraction for each muscle group. | 0 | 16 | 0 | 16 | 16 | 16 |
| EG003 | Exercise Intervention and Placebo | 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 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. Nicotinamide Riboside: Investigators will use (Good Manufacturing Process) GMP-grade 300 mg capsules of the dietary supplement nicotinamide riboside, distributed by ChromaDex, Inc., Irvine, CA. 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: On aerobic 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 days, subjects will be instructed to complete circuits of resistance exercises. Training intensity (as determined by graded resistance bands) will be maintained at 60% of pre-training maximal voluntary contraction for each muscle group. | 0 | 16 | 0 | 16 | 14 | 16 |
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| Cardiac Disorders | Cardiac disorders | CTCAE (5.0) | Systematic Assessment | Tachycardia, Other |
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| Eye Disorders | Eye disorders | CTCAE (5.0) | Systematic Assessment | Blurred Vision, Other |
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| General Disorders | General disorders | CTCAE (5.0) | Systematic Assessment | Fatigue, Fever, Pain, Other |
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| Upper Respiratory Infection | Infections and infestations | CTCAE (5.0) | Systematic Assessment |
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| Injury and Procedural Complications | Injury, poisoning and procedural complications | CTCAE (5.0) | Systematic Assessment | Fall, Other |
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| Investigations | Infections and infestations | CTCAE (5.0) | Systematic Assessment | ALT Increase, AST Increase, Other |
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| Metabolism and Nutrition Disorders | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment | Glucose Intolerance, Hyperglycemia, Hypoglycemia |
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| Musculoskeletal and Connective Tissue Disorders | Musculoskeletal and connective tissue disorders | CTCAE (5.0) | Systematic Assessment | Arthralgia, Back Pain, Muscle Cramp, Myalgia |
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| Nervous System Disorders | Nervous system disorders | CTCAE (5.0) | Systematic Assessment | Dizziness, Dysarthria, Headache |
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| Psychiatric Disorders | Psychiatric disorders | CTCAE (5.0) | Systematic Assessment | Depression, Insomnia, Irritability |
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| Respiratory, thoracic, and mediastinal disorders | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Systematic Assessment | Epistaxis, Sore Throat |
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| Skin and Subcutaneous Tissue Disorders | Skin and subcutaneous tissue disorders | CTCAE (5.0) | Systematic Assessment | Dry Skin, Other |
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| Flushing | Vascular disorders | CTCAE (5.0) | Systematic Assessment |
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Not provided
Not provided