Peripheral Artery Disease
Conditions
Keywords
Peripheral Artery Disease, PAD, Resveratrol, Nicotinamide riboside (NR), Six-minute walk, Functional performance
Brief summary
NICE is a randomized clinical trial that will examine the effects of nicotinamide riboside (NR) both with and without resveratrol to test whether, among people with PAD, NR significantly improves walking performance more than placebo and whether NR combined with resveratrol significantly improves walking performance more than placebo. If findings support the hypotheses, results will be used to design a large, definitive randomized clinical. The study will randomize 90 participants with PAD to one of the following three groups: NR + resveratrol, NR + placebo, or placebo + placebo.
Interventions
DRUGNicotinamide riboside
Participants randomized to the NR + resveratrol arm or the NR + placebo arm of the study will receive 1,000 mg of NR daily for six months.
DRUGResveratrol
Participants randomized to the NR + resveratrol arm of the study will receive 125 mg of resveratrol daily for six months.
OTHERPlacebo
Participants randomized to the NR + placebo arm of the study will receiving placebo pills that are identical in appearance to resveratrol. Participants randomized to the placebo + placebo arm of the study will receive pills that are identical in appearance to NR and resveratrol. Participants will receive placebo pills daily for six months.
Sponsors
American Heart Association
Northwestern University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
All participants will have PAD. PAD will be defined as the following: 1) An ankle-brachial index (ABI) \<=0.90 at the baseline study visit or 2) Vascular laboratory evidence or angiographic evidence of PAD. Inclusion based on prior vascular laboratory evidence will be determined by the study principal investigator and includes, for example, a toe brachial index (TBI) \< 0.70, Duplex measure showing 70% stenosis or great, a post heel-rise or post-exercise ABI drop of 20% or greater, or ABI values \<= 0.90. Angiographic evidence of PAD consists of a stenosis of 70% or greater in a lower extremity artery.
Exclusion criteria
1. Above- or below-knee amputation. 2. Critical limb ischemia. 3. Wheelchair-bound or requiring a walker to ambulate. 4. Walking is limited by a symptom other than PAD. 5. Current foot ulcer on bottom of foot. 6. End stage renal disease defined as a GFR less than 20 ml/min/1.73 M2. 7. Significant liver impairment defined as two or more hepatic function enzymes \>3.0 times the upper limit of normal. \[NOTE: participants who meet this criterion may undergo a re-test of hepatic function tests to determine whether initially elevated hepatic enzymes represented a transient or spurious phenomenon.\] 8. Failure to successfully complete the 2-week study run-in. 9. Planned lower extremity revascularization, orthopedic surgery, or other major surgery during the next six months. 10. Lower extremity revascularization, orthopedic surgery, cardiovascular event, coronary revascularization, or other major surgery in the previous three months. 11. Participation in supervised treadmill exercise during the previous three months. 12. Major medical illness including renal disease requiring dialysis, lung disease requiring oxygen, Parkinson's disease, a life-threatening illness with life expectancy less than six months, or cancer requiring treatment in the previous two years. \[NOTE: potential participants may still qualify if they have had treatment for an early stage cancer in the past two years and the prognosis is excellent. Participants who only use oxygen at night may still qualify.\] 13. Mini-Mental Status Examination (MMSE) score \<23 or dementia. 14. Participation in or completion of a clinical trial in the previous three months. \[NOTE: after completing a stem cell or gene therapy intervention, participants will become eligible after the final study follow-up visit of the stem cell or gene therapy study so long as at least six months have passed since the final intervention administration. After completing a supplement or drug therapy (other than stem cell or gene therapy), participants will be eligible after the final study follow-up visit as long as at least three months have passed since the final intervention of the trial.\] 15. Currently taking a dose of 250 mg or more of nicotinamide riboside, vitamin B3, niacin. Currently taking a slow-release form of niacin. Currently taking resveratrol or has taken any these drug(s) in past six months. Participants taking a multi-vitamin will not be excluded if the dose of vitamin B3 is less than 250 mgs. 16. Increase in angina or angina at rest 17. Non-English speaking. 18. Visual impairment that limits walking ability. 19. Women who are pregnant or who are pre-menopausal will not be eligible. 20. In addition to the above criteria, investigator discretion will be used to determine if the trial is unsafe or not a good fit for the potential participant. Potentially eligible participants will be advised that Medicare coverage for 12 weeks of supervised treadmill exercise is now available. Potential participants who have not participated in supervised treadmill exercise covered by Medicare and who desire to participate will be referred back to their physician for follow-up. These individuals may become eligible six months after they complete supervised treadmill exercise. Vulnerable populations (fetuses, pregnant women, children, prisoners, and institutionalized persons) and adults unable to consent will not be included in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Six-minute Walk Distance (NR Alone vs. Placebo) | Baseline to 6-month follow-up | Among participants with PAD, investigators will determine whether NR alone improves six-minute walk distance at 6-month follow-up, compared to placebo. |
| Six-minute Walk Distance (NR/Resveratrol vs. Placebo) | Baseline to 6-month follow-up | Among participants with PAD, investigators will determine whether NR combined with resveratrol improves six-minute walk performance at 6-month follow-up, compared to placebo. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Physical Activity (NR Alone vs. Placebo) | Baseline to 6-month follow-up | Among participants with PAD, investigators will determine whether NR alone improves physical activity at 6-month follow-up, compared to placebo. The physical activity outcome was measured with the ActiGraph, in Activity Units. Higher scores indicate greater activity. The lowest possible score is zero, indicating sedentary time. |
| Physical Activity (NR/Resveratrol vs. Placebo) | Baseline to 6-month follow-up | Among participants with PAD, investigators will determine whether NR combined with resveratrol improves physical activity at 6-month follow-up, compared to placebo. The physical activity outcome was measured with the ActiGraph, in Activity Units. Higher scores indicate greater activity. The lowest possible score is zero, indicating sedentary time. |
| Physical Activity (NR/Resveratrol vs. NR Alone) | Baseline to 6-month follow-up | Among participants with PAD, investigators will determine whether NR combined with resveratrol improves physical activity at 6-month follow-up, compared to NR alone.. The physical activity outcome was measured with the ActiGraph, in Activity Units. Higher scores indicate greater activity. The lowest possible score is zero, indicating sedentary time. |
| Walking Impairment Questionnaire (WIQ) Distance Score (NR/Resveratrol vs. NR Alone) | Baseline to 6-month follow-up | Among participants with PAD, investigators will determine whether NR combined with resveratrol improves the Walking Impairment Questionnaire (WIQ) distance score at 6-month follow-up, compared to NR alone. The WIQ is a well validated questionnaire that measures patient-reported walking limitations in distance and speed and stair-climbing. They are scored on a 0-100 scale and that 100 indicates the best possible score. |
| Maximal Treadmill Walking Time (NR/Resveratrol vs. NR Alone) | Baseline to 6-month follow-up | Among participants with PAD, investigators will determine whether NR combined with resveratrol improves maximal treadmill walking time at 6-month follow-up, compared to NR alone. |
| Six-minute Walk Distance (NR/Resveratrol or NR Alone vs. Placebo) | Baseline to 3-month follow-up | Participants with PAD who received NR alone and those who received NR + resveratrol will be combined into one group and compared to the group receiving placebo, to determine whether NR alone or NR+ resveratrol (combined group)have greater improvement in six-minute walk distance, compared to those randomized to placebo. Mixed model for repeated measures is applied to Placebo vs. 2 NR groups combined. The reported results of within group change and between group difference are Least Squares Mean (Standard Error) from the model adjusted for baseline six-minute walk + age + sex + race + resveratrol usage. |
| Maximal Treadmill Walking Time (NR/Resveratrol or NR Alone vs. Placebo) | Baseline to 6-month follow-up | Participants with PAD who received NR alone and those who received NR + resveratrol will be combined into one group and compared to the group receiving placebo, to determine whether NR alone or NR+ resveratrol (combined group)have greater improvement in maximal treadmill walking time, compared to those randomized to placebo. |
| Walking Impairment Questionnaire (WIQ) Distance Score (NR/Resveratrol or NR Alone vs. Placebo) | Baseline to 6-month follow-up | Participants with PAD who received NR alone and those who received NR + resveratrol will be combined into one group and compared to the group receiving placebo, to determine whether NR alone or NR+ resveratrol (combined group)have greater improvement in Walking Impairment Questionnaire distance score, compared to those randomized to placebo. The WIQ is a well validated questionnaire that measures patient-reported walking limitations in distance and speed and stair-climbing. They are scored on a 0-100 scale and that 100 indicates the best possible score. |
| Physical Activity (NR/Resveratrol or NR Alone vs. Placebo) | Baseline to 6-month follow-up | Participants with PAD who received NR alone and those who received NR + resveratrol will be combined into one group and compared to the group receiving placebo, to determine whether NR alone or NR+ resveratrol (combined group)have greater improvement in physical activity, compared to those randomized to placebo. The physical activity outcome was measured with the ActiGraph, in Activity Units. Higher scores indicate greater activity. The lowest possible score is zero, indicating sedentary time. Mixed model for repeated measures is applied to Placebo vs. 2 NR groups combined. The reported results of within group change and between group difference are Least Squares Mean (Standard Error) from the model adjusted for baseline six-minute walk + age + sex + race + resveratrol usage. |
| NAD+ Abundance in Gastrocnemius Muscle (NR/Resveratrol or NR Alone vs. Placebo) | Baseline to 6-month follow-up | The outcome measure is the comparison of 6-month change in gastrocnemius muscle biopsy measures of NAD+ abundance between NR and placebo and between NR + resveratrol and placebo. Participants with PAD who received NR alone and those who received NR + resveratrol will be combined into one group and compared to the group receiving placebo, to determine whether NR alone or NR+ resveratrol (combined group) have greater improvement in NAD+ abundance, compared to those randomized to placebo. Measurements of NAD+ abundance were completed using High Performance Liquid Chromatography (HPLC) with a Shimadzu LC-20A pump and UV-VIS detector using a Supelco LC-18-Tcolumn, normalized to muscle weight. |
| Satellite Cell Abundance in Gastrocnemius Muscle (NR/Resveratrol or NR Alone vs. Placebo) | Baseline to 6-month follow-up | The outcome measure is the comparison of 6-month changes in gastrocnemius muscle biopsy measures of satellite cell abundance between NR and placebo and between NR + resveratrol and placebo. Participants with PAD who received NR alone and those who received NR + resveratrol will be combined into one group and compared to the group receiving placebo, to determine whether NR alone or NR+ resveratrol (combined group) have greater improvement in satellite cell abundance, compared to those randomized to placebo. Satellite cell abundance was measured via density (satellite cells/100 fibers) using antibodies against: Pax7, type 1 myosin, and laminin. |
| Gastrocnemius Muscle Fiber Phenotype(NR/Resveratrol or NR Alone vs. Placebo) | Baseline to 6-month follow-up | The outcome measure is the comparison of 6-month changes in gastrocnemius muscle biopsy measures of Percent Type 1 myofibers (%) between NR and placebo and between NR + resveratrol and placebo. Participants with PAD who received NR alone and those who received NR + resveratrol will be combined into one group and compared to the group receiving placebo, to determine whether NR alone or NR+ resveratrol (combined group) have greater improvement in muscle fiber phenotype, compared to those randomized to placebo. Measurements of fiber type % were determined on frozen muscle sections using antibodies against: Pax7, type 1 myosin, and laminin. Mixed model for repeated measures is applied to Placebo vs. 2 NR groups combined. The reported results of within group change and between group difference are Least Squares Mean (Standard Error) from the model adjusted for baseline six-minute walk + age + sex + race + resveratrol usage. |
| Six-minute Walk Distance (NR Alone vs. Placebo) | Baseline to 3-month follow-up | Among participants with PAD, investigators will determine whether NR alone improves six-minute walk performance at 3-month follow-up, compared to placebo. |
| Six-minute Walk Distance (NR/Resveratrol vs. Placebo) | Baseline to 3-month follow-up | Among participants with PAD, investigators will determine whether NR combined with resveratrol improves six-minute walk performance at 3-month follow-up, compared to placebo. |
| Six-minute Walk Distance (NR/Resveratrol vs. NR Alone) | Baseline to 3-month follow-up | Among participants with PAD, investigators will determine whether NR combined with resveratrol improves six-minute walk performance at 3-month follow-up, compared to NR alone. |
| Maximal Treadmill Walking Time (NR Alone vs. Placebo) | Baseline to 6-month follow-up | Among participants with PAD, investigators will determine whether NR alone improves maximal treadmill walking time at 6-month follow-up, compared to placebo. |
| Walking Impairment Questionnaire (WIQ) Distance Score (NR Alone vs. Placebo) | Baseline to 6-month follow-up | Among participants with PAD, investigators will determine whether NR alone improves the Walking Impairment Questionnaire (WIQ) distance score at 6-month follow-up, compared to placebo. The WIQ is a well validated questionnaire that measures patient-reported walking limitations in distance and speed and stair-climbing. They are scored on a 0-100 scale and that 100 indicates the best possible score. |
| Maximal Treadmill Walking Time (NR/Resveratrol vs. Placebo) | Baseline to 6-month follow-up | Among participants with PAD, investigators will determine whether NR combined with resveratrol improves maximal treadmill walking time at 6-month follow-up, compared to placebo. |
| Walking Impairment Questionnaire (WIQ) Distance Score (NR/Resveratrol vs. Placebo) | Baseline to 6-month follow-up | Among participants with PAD, investigators will determine whether NR combined with resveratrol improves the Walking Impairment Questionnaire distance score at 6-month follow-up, compared to placebo. The WIQ is a well validated questionnaire that measures patient-reported walking limitations in distance and speed and stair-climbing. They are scored on a 0-100 scale and that 100 indicates the best possible score. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Walking Impairment Questionnaire (WIQ) Speed Score (NR Alone vs. Placebo) | Baseline to 6-month follow-up | Among participants with PAD, investigators will determine whether NR alone improves the Walking Impairment Questionnaire speed and stair climbing score at 6-month follow-up, compared to placebo. The WIQ is a well validated questionnaire that measures patient-reported walking limitations in distance and speed and stair-climbing. They are scored on a 0-100 scale and that 100 indicates the best possible score. |
| Short-Form Physical Functioning (SF-36) Score (NR Alone vs. Placebo) | Baseline to 6-month follow-up | Among participants with PAD, investigators will determine whether NR alone improves the Walking Impairment Questionnaire speed and stair climbing scores and the Short-Form Physical Functioning score at 6-month follow-up, compared to placebo. The SF-36 measures health status. The score range is 0-100, where 100 is best. |
| Walking Impairment Questionnaire (WIQ) Stair Climbing Score (NR/Resveratrol vs. Placebo) | Baseline to 6-month follow-up | Among participants with PAD, investigators will determine whether NR combined with resveratrol improves the Walking Impairment Questionnaire speed and stair climbing scores at 6-month follow-up, compared to placebo. The WIQ is a well validated questionnaire that measures patient-reported walking limitations in distance and speed and stair-climbing. They are scored on a 0-100 scale and that 100 indicates the best possible score. |
| Short-Form Physical Functioning (SF-36) Score (NR/Resveratrol vs. Placebo) | Baseline to 6-month follow-up | Among participants with PAD, investigators will determine whether NR combined with resveratrol improves the Short-Form Physical Functioning score at 6-month follow-up, compared to placebo. The SF-36 measures health status. The score range is 0-100, where 100 is best. |
| Walking Impairment Questionnaire (WIQ) Speed Score (NR/Resveratrol vs. NR Alone) | Baseline to 6-month follow-up | Among participants with PAD, investigators will determine whether NR combined with resveratrol improves the Walking Impairment Questionnaire speed and stair climbing score at 6-month follow-up, compared to NR alone. The WIQ is a well validated questionnaire that measures patient-reported walking limitations in distance and speed and stair-climbing. They are scored on a 0-100 scale and that 100 indicates the best possible score. |
| Short-Form Physical Functioning (SF-36) Score (NR/Resveratrol vs. NR Alone) | Baseline to 6-month follow-up | Among participants with PAD, investigators will determine whether NR combined with resveratrol improves the Walking Impairment Questionnaire speed and stair climbing scores and the Short-Form Physical Functioning score at 6-month follow-up, compared to NR alone. The SF-36 measures health status. The score range is 0-100, where 100 is best. |
| Walking Impairment Questionnaire (WIQ) Speed Score (NR/Resveratrol or NR Alone vs. Placebo) | Baseline to 6-month follow-up | Participants with PAD who received NR alone and those who received NR + resveratrol will be combined into one group and compared to the group receiving placebo, to determine whether NR alone or NR+ resveratrol (combined group) have greater improvement in the Walking Impairment Questionnaire (WIQ) speed and stair climbing score at 6-month follow-up, compared to placebo. The WIQ is a well validated questionnaire that measures patient-reported walking limitations in distance and speed and stair-climbing. They are scored on a 0-100 scale and that 100 indicates the best possible score. |
| Short-Form Physical Functioning (SF-36) Score (NR/Resveratrol or NR Alone vs. Placebo) | Baseline to 6-month follow-up | Participants with PAD who received NR alone and those who received NR + resveratrol will be combined into one group and compared to the group receiving placebo, to determine whether NR alone or NR+ resveratrol (combined group) have greater improvement in the Short-Form Physical Functioning score at 6-month follow-up, compared to placebo. The SF-36 measures health status. The score range is 0-100, where 100 is best. |
| NAD+ Abundance in Gastrocnemius Muscle (NR/Resveratrol vs. Placebo and NR vs. Placebo) | Baseline to 6-month follow-up | Investigators will perform calf muscle biopsies to determine whether among participants with PAD, those randomized to NR + resveratrol and NR alone have increased calf muscle NAD+ abundance, compared to the placebo group. Measurements of NAD+ abundance were completed using High Performance Liquid Chromatography (HPLC) with a Shimadzu LC-20A pump and UV-VIS detector using a Supelco LC-18-Tcolumn, normalized to muscle weight. |
| Muscle Fiber Phenotype in Gastrocnemius Muscle (NR/Resveratrol vs. Placebo and NR vs. Placebo) | Baseline to 6-month follow-up | Investigators will perform calf muscle biopsies to determine whether among participants with PAD, those randomized to NR + resveratrol and NR alone have improved muscle fiber phenotype (Percent Type 1 myofibers (%)), compared to the placebo group. Measurements of fiber type % were determined on frozen muscle sections using antibodies against: Pax7, type 1 myosin, and laminin. |
| Gastrocnemius Muscle Satellite Cell Abundance (NR/Resveratrol vs. Placebo and NR vs. Placebo) | Baseline to 6-month follow-up | Investigators will perform calf muscle biopsies to determine whether among participants with PAD, those randomized to NR + resveratrol and NR alone have increased satellite cell abundance compared to the placebo group. Satellite cell abundance was measured via density (satellite cells/100 fibers) using antibodies against: Pax7, type 1 myosin, and laminin. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nicotinamide Riboside + Resveratrol Participants randomized to the NR + resveratrol arm of the study will receive 1,000 mg of NR and 125 mg of resveratrol daily for six months.
Nicotinamide riboside: Participants randomized to the NR + resveratrol arm or the NR + placebo arm of the study will receive 1,000 mg of NR daily for six months.
Resveratrol: Participants randomized to the NR + resveratrol arm of the study will receive 125 mg of resveratrol daily for six months. | 33 |
| Nicotinamide Riboside + Placebo Participants randomized to the NR + placebo arm of the study will receive 1,000 mg of NR and a placebo daily for six months.
Nicotinamide riboside: Participants randomized to the NR + resveratrol arm or the NR + placebo arm of the study will receive 1,000 mg of NR daily for six months.
Placebo: Participants randomized to the NR + placebo arm of the study will receiving placebo pills that are identical in appearance to resveratrol. Participants randomized to the placebo + placebo arm of the study will receive pills that are identical in appearance to NR and resveratrol. Participants will receive placebo pills daily for six months. | 28 |
| Placebo + Placebo Participants randomized to the placebo + placebo arm of study will receive placebo pills.
Placebo: Participants randomized to the NR + placebo arm of the study will receiving placebo pills that are identical in appearance to resveratrol. Participants randomized to the placebo + placebo arm of the study will receive pills that are identical in appearance to NR and resveratrol. Participants will receive placebo pills daily for six months. | 29 |
| Total | 90 |
Baseline characteristics
| Characteristic | Nicotinamide Riboside + Resveratrol | Total | Placebo + Placebo | Nicotinamide Riboside + Placebo |
|---|---|---|---|---|
| 6-min walk distance | 336.61 meters STANDARD_DEVIATION 80.75 | 333.86 meters STANDARD_DEVIATION 97.9 | 325.60 meters STANDARD_DEVIATION 112.51 | 339.18 meters STANDARD_DEVIATION 103.07 |
| Age, Continuous | 70.73 years STANDARD_DEVIATION 8.97 | 71.18 years STANDARD_DEVIATION 9.1 | 69.72 years STANDARD_DEVIATION 8.29 | 73.21 years STANDARD_DEVIATION 9.97 |
| Ankle brachial index | 0.67 ratio STANDARD_DEVIATION 0.2 | 0.68 ratio STANDARD_DEVIATION 0.19 | 0.64 ratio STANDARD_DEVIATION 0.18 | 0.72 ratio STANDARD_DEVIATION 0.18 |
| Body mass index | 29.30 kg/m^2 STANDARD_DEVIATION 6.66 | 29.44 kg/m^2 STANDARD_DEVIATION 5.76 | 30.37 kg/m^2 STANDARD_DEVIATION 6.39 | 28.65 kg/m^2 STANDARD_DEVIATION 3.61 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 5 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants | 83 Participants | 27 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 19 Participants | 43 Participants | 16 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 13 Participants | 44 Participants | 12 Participants | 19 Participants |
| Sex: Female, Male Female | 14 Participants | 42 Participants | 16 Participants | 12 Participants |
| Sex: Female, Male Male | 19 Participants | 48 Participants | 13 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 33 | 0 / 28 | 0 / 29 |
| other Total, other adverse events | 24 / 33 | 18 / 28 | 21 / 29 |
| serious Total, serious adverse events | 9 / 33 | 6 / 28 | 6 / 29 |
Outcome results
Primary
Six-minute Walk Distance (NR Alone vs. Placebo)
Among participants with PAD, investigators will determine whether NR alone improves six-minute walk distance at 6-month follow-up, compared to placebo.
Time frame: Baseline to 6-month follow-up
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide Riboside + Resveratrol | Six-minute Walk Distance (NR Alone vs. Placebo) | -6.93 meters | Standard Error 7.84 |
| Nicotinamide Riboside + Placebo | Six-minute Walk Distance (NR Alone vs. Placebo) | 7.00 meters | Standard Error 8.69 |
| Placebo + Placebo | Six-minute Walk Distance (NR Alone vs. Placebo) | -10.58 meters | Standard Error 8.45 |
p-value: 0.0775Mixed Models Analysis
Primary
Six-minute Walk Distance (NR/Resveratrol vs. Placebo)
Among participants with PAD, investigators will determine whether NR combined with resveratrol improves six-minute walk performance at 6-month follow-up, compared to placebo.
Time frame: Baseline to 6-month follow-up
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide Riboside + Resveratrol | Six-minute Walk Distance (NR/Resveratrol vs. Placebo) | -6.93 meters | Standard Error 7.84 |
| Nicotinamide Riboside + Placebo | Six-minute Walk Distance (NR/Resveratrol vs. Placebo) | 7.00 meters | Standard Error 8.69 |
| Placebo + Placebo | Six-minute Walk Distance (NR/Resveratrol vs. Placebo) | -10.58 meters | Standard Error 8.45 |
p-value: 0.3762Mixed Models Analysis
Secondary
Gastrocnemius Muscle Fiber Phenotype(NR/Resveratrol or NR Alone vs. Placebo)
The outcome measure is the comparison of 6-month changes in gastrocnemius muscle biopsy measures of Percent Type 1 myofibers (%) between NR and placebo and between NR + resveratrol and placebo. Participants with PAD who received NR alone and those who received NR + resveratrol will be combined into one group and compared to the group receiving placebo, to determine whether NR alone or NR+ resveratrol (combined group) have greater improvement in muscle fiber phenotype, compared to those randomized to placebo. Measurements of fiber type % were determined on frozen muscle sections using antibodies against: Pax7, type 1 myosin, and laminin. Mixed model for repeated measures is applied to Placebo vs. 2 NR groups combined. The reported results of within group change and between group difference are Least Squares Mean (Standard Error) from the model adjusted for baseline six-minute walk + age + sex + race + resveratrol usage.
Time frame: Baseline to 6-month follow-up
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide Riboside + Resveratrol | Gastrocnemius Muscle Fiber Phenotype(NR/Resveratrol or NR Alone vs. Placebo) | -2.88 percentage | Standard Error 3.58 |
| Nicotinamide Riboside + Placebo | Gastrocnemius Muscle Fiber Phenotype(NR/Resveratrol or NR Alone vs. Placebo) | -8.09 percentage | Standard Error 5.75 |
p-value: 0.2378ANCOVA
Secondary
Maximal Treadmill Walking Time (NR Alone vs. Placebo)
Among participants with PAD, investigators will determine whether NR alone improves maximal treadmill walking time at 6-month follow-up, compared to placebo.
Time frame: Baseline to 6-month follow-up
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide Riboside + Resveratrol | Maximal Treadmill Walking Time (NR Alone vs. Placebo) | 0.57 minutes | Standard Error 1.11 |
| Nicotinamide Riboside + Placebo | Maximal Treadmill Walking Time (NR Alone vs. Placebo) | 0.89 minutes | Standard Error 0.94 |
| Placebo + Placebo | Maximal Treadmill Walking Time (NR Alone vs. Placebo) | -1.17 minutes | Standard Error 0.97 |
p-value: 0.0752ANCOVA
Secondary
Maximal Treadmill Walking Time (NR/Resveratrol or NR Alone vs. Placebo)
Participants with PAD who received NR alone and those who received NR + resveratrol will be combined into one group and compared to the group receiving placebo, to determine whether NR alone or NR+ resveratrol (combined group)have greater improvement in maximal treadmill walking time, compared to those randomized to placebo.
Time frame: Baseline to 6-month follow-up
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide Riboside + Resveratrol | Maximal Treadmill Walking Time (NR/Resveratrol or NR Alone vs. Placebo) | -1.33 minutes | Standard Error 1.28 |
| Nicotinamide Riboside + Placebo | Maximal Treadmill Walking Time (NR/Resveratrol or NR Alone vs. Placebo) | 0.73 minutes | Standard Error 0.64 |
Comparison: Mixed model for repeated measures is applied to Placebo vs. 2 NR groups combined. The reported results of within group change and between group difference are Least Squares Mean (Standard Error) from the model adjusted for baseline six-minute walk + age + sex + race + resveratrol usage.p-value: 0.0752ANCOVA
Secondary
Maximal Treadmill Walking Time (NR/Resveratrol vs. NR Alone)
Among participants with PAD, investigators will determine whether NR combined with resveratrol improves maximal treadmill walking time at 6-month follow-up, compared to NR alone.
Time frame: Baseline to 6-month follow-up
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide Riboside + Resveratrol | Maximal Treadmill Walking Time (NR/Resveratrol vs. NR Alone) | 0.57 minutes | Standard Error 1.11 |
| Nicotinamide Riboside + Placebo | Maximal Treadmill Walking Time (NR/Resveratrol vs. NR Alone) | 0.89 minutes | Standard Error 0.94 |
| Placebo + Placebo | Maximal Treadmill Walking Time (NR/Resveratrol vs. NR Alone) | -1.17 minutes | Standard Error 0.97 |
p-value: 0.5777ANCOVA
Secondary
Maximal Treadmill Walking Time (NR/Resveratrol vs. Placebo)
Among participants with PAD, investigators will determine whether NR combined with resveratrol improves maximal treadmill walking time at 6-month follow-up, compared to placebo.
Time frame: Baseline to 6-month follow-up
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide Riboside + Resveratrol | Maximal Treadmill Walking Time (NR/Resveratrol vs. Placebo) | 0.57 minutes | Standard Error 1.11 |
| Nicotinamide Riboside + Placebo | Maximal Treadmill Walking Time (NR/Resveratrol vs. Placebo) | 0.89 minutes | Standard Error 0.94 |
| Placebo + Placebo | Maximal Treadmill Walking Time (NR/Resveratrol vs. Placebo) | -1.17 minutes | Standard Error 0.97 |
p-value: 0.1249ANCOVA
Secondary
NAD+ Abundance in Gastrocnemius Muscle (NR/Resveratrol or NR Alone vs. Placebo)
The outcome measure is the comparison of 6-month change in gastrocnemius muscle biopsy measures of NAD+ abundance between NR and placebo and between NR + resveratrol and placebo. Participants with PAD who received NR alone and those who received NR + resveratrol will be combined into one group and compared to the group receiving placebo, to determine whether NR alone or NR+ resveratrol (combined group) have greater improvement in NAD+ abundance, compared to those randomized to placebo. Measurements of NAD+ abundance were completed using High Performance Liquid Chromatography (HPLC) with a Shimadzu LC-20A pump and UV-VIS detector using a Supelco LC-18-Tcolumn, normalized to muscle weight.
Time frame: Baseline to 6-month follow-up
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide Riboside + Resveratrol | NAD+ Abundance in Gastrocnemius Muscle (NR/Resveratrol or NR Alone vs. Placebo) | 43.83 pmol/mg | Standard Error 26.15 |
| Nicotinamide Riboside + Placebo | NAD+ Abundance in Gastrocnemius Muscle (NR/Resveratrol or NR Alone vs. Placebo) | 8.70 pmol/mg | Standard Error 17.92 |
p-value: 0.8401ANCOVA
Secondary
Physical Activity (NR Alone vs. Placebo)
Among participants with PAD, investigators will determine whether NR alone improves physical activity at 6-month follow-up, compared to placebo. The physical activity outcome was measured with the ActiGraph, in Activity Units. Higher scores indicate greater activity. The lowest possible score is zero, indicating sedentary time.
Time frame: Baseline to 6-month follow-up
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide Riboside + Resveratrol | Physical Activity (NR Alone vs. Placebo) | -7743 Activity count per day | Standard Error 6478 |
| Nicotinamide Riboside + Placebo | Physical Activity (NR Alone vs. Placebo) | 4094 Activity count per day | Standard Error 7109 |
| Placebo + Placebo | Physical Activity (NR Alone vs. Placebo) | -6901 Activity count per day | Standard Error 6889 |
p-value: 0.1402ANCOVA
Secondary
Physical Activity (NR/Resveratrol or NR Alone vs. Placebo)
Participants with PAD who received NR alone and those who received NR + resveratrol will be combined into one group and compared to the group receiving placebo, to determine whether NR alone or NR+ resveratrol (combined group)have greater improvement in physical activity, compared to those randomized to placebo. The physical activity outcome was measured with the ActiGraph, in Activity Units. Higher scores indicate greater activity. The lowest possible score is zero, indicating sedentary time. Mixed model for repeated measures is applied to Placebo vs. 2 NR groups combined. The reported results of within group change and between group difference are Least Squares Mean (Standard Error) from the model adjusted for baseline six-minute walk + age + sex + race + resveratrol usage.
Time frame: Baseline to 6-month follow-up
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide Riboside + Resveratrol | Physical Activity (NR/Resveratrol or NR Alone vs. Placebo) | -12819 Activity count per day | Standard Error 8528 |
| Nicotinamide Riboside + Placebo | Physical Activity (NR/Resveratrol or NR Alone vs. Placebo) | -1824 Activity count per day | Standard Error 4763 |
Comparison: Mixed model for repeated measures is applied to Placebo vs. 2 NR groups combined. The reported results of within group change and between group difference are Least Squares Mean (Standard Error) from the model adjusted for baseline six-minute walk + age + sex + race + resveratrol usage.p-value: 0.1402ANCOVA
Secondary
Physical Activity (NR/Resveratrol vs. NR Alone)
Among participants with PAD, investigators will determine whether NR combined with resveratrol improves physical activity at 6-month follow-up, compared to NR alone.. The physical activity outcome was measured with the ActiGraph, in Activity Units. Higher scores indicate greater activity. The lowest possible score is zero, indicating sedentary time.
Time frame: Baseline to 6-month follow-up
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide Riboside + Resveratrol | Physical Activity (NR/Resveratrol vs. NR Alone) | -7743 Activity count per day | Standard Error 6478 |
| Nicotinamide Riboside + Placebo | Physical Activity (NR/Resveratrol vs. NR Alone) | 4094 Activity count per day | Standard Error 7109 |
| Placebo + Placebo | Physical Activity (NR/Resveratrol vs. NR Alone) | -6901 Activity count per day | Standard Error 6889 |
p-value: 0.8866ANCOVA
Secondary
Physical Activity (NR/Resveratrol vs. Placebo)
Among participants with PAD, investigators will determine whether NR combined with resveratrol improves physical activity at 6-month follow-up, compared to placebo. The physical activity outcome was measured with the ActiGraph, in Activity Units. Higher scores indicate greater activity. The lowest possible score is zero, indicating sedentary time.
Time frame: Baseline to 6-month follow-up
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide Riboside + Resveratrol | Physical Activity (NR/Resveratrol vs. Placebo) | -7743 Activity count per day | Standard Error 6478 |
| Nicotinamide Riboside + Placebo | Physical Activity (NR/Resveratrol vs. Placebo) | 4094 Activity count per day | Standard Error 7109 |
| Placebo + Placebo | Physical Activity (NR/Resveratrol vs. Placebo) | -6901 Activity count per day | Standard Error 6889 |
p-value: 0.5352ANCOVA
Secondary
Satellite Cell Abundance in Gastrocnemius Muscle (NR/Resveratrol or NR Alone vs. Placebo)
The outcome measure is the comparison of 6-month changes in gastrocnemius muscle biopsy measures of satellite cell abundance between NR and placebo and between NR + resveratrol and placebo. Participants with PAD who received NR alone and those who received NR + resveratrol will be combined into one group and compared to the group receiving placebo, to determine whether NR alone or NR+ resveratrol (combined group) have greater improvement in satellite cell abundance, compared to those randomized to placebo. Satellite cell abundance was measured via density (satellite cells/100 fibers) using antibodies against: Pax7, type 1 myosin, and laminin.
Time frame: Baseline to 6-month follow-up
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide Riboside + Resveratrol | Satellite Cell Abundance in Gastrocnemius Muscle (NR/Resveratrol or NR Alone vs. Placebo) | -11.95 satellite cells/100 fibers | Standard Error 5.18 |
| Nicotinamide Riboside + Placebo | Satellite Cell Abundance in Gastrocnemius Muscle (NR/Resveratrol or NR Alone vs. Placebo) | -0.81 satellite cells/100 fibers | Standard Error 3.32 |
Comparison: Mixed model for repeated measures is applied to Placebo vs. 2 NR groups combined. The reported results of within group change and between group difference are Least Squares Mean (Standard Error) from the model adjusted for baseline six-minute walk + age + sex + race + resveratrol usage.p-value: 0.0602ANCOVA
Secondary
Six-minute Walk Distance (NR Alone vs. Placebo)
Among participants with PAD, investigators will determine whether NR alone improves six-minute walk performance at 3-month follow-up, compared to placebo.
Time frame: Baseline to 3-month follow-up
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide Riboside + Resveratrol | Six-minute Walk Distance (NR Alone vs. Placebo) | 2.99 meters | Standard Error 7.67 |
| Nicotinamide Riboside + Placebo | Six-minute Walk Distance (NR Alone vs. Placebo) | 4.78 meters | Standard Error 8.28 |
| Placebo + Placebo | Six-minute Walk Distance (NR Alone vs. Placebo) | -17.64 meters | Standard Error 8.03 |
p-value: 0.0294Mixed Models Analysis
Secondary
Six-minute Walk Distance (NR/Resveratrol or NR Alone vs. Placebo)
Participants with PAD who received NR alone and those who received NR + resveratrol will be combined into one group and compared to the group receiving placebo, to determine whether NR alone or NR+ resveratrol (combined group)have greater improvement in six-minute walk distance, compared to those randomized to placebo. Mixed model for repeated measures is applied to Placebo vs. 2 NR groups combined. The reported results of within group change and between group difference are Least Squares Mean (Standard Error) from the model adjusted for baseline six-minute walk + age + sex + race + resveratrol usage.
Time frame: Baseline to 3-month follow-up
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide Riboside + Resveratrol | Six-minute Walk Distance (NR/Resveratrol or NR Alone vs. Placebo) | -21.34 meters | Standard Error 9.66 |
| Nicotinamide Riboside + Placebo | Six-minute Walk Distance (NR/Resveratrol or NR Alone vs. Placebo) | 3.92 meters | Standard Error 5.61 |
Comparison: Mixed models for repeated measures were used to compare 3-month change in 6MW distance between the NR/resveratrol vs placebo groups and between the NR alone vs placebo groups using baseline, 3-month, and 6-month values, adjusted for age, sex, race, and baseline 6MW.p-value: 0.0153Mixed Models Analysis
Secondary
Six-minute Walk Distance (NR/Resveratrol or NR Alone vs. Placebo)
Participants with PAD who received NR alone and those who received NR + resveratrol will be combined into one group and compared to the group receiving placebo, to determine whether NR alone or NR+ resveratrol (combined group)have greater improvement in six-minute walk distance, compared to those randomized to placebo. Mixed model for repeated measures is applied to Placebo vs. 2 NR groups combined. The reported results of within group change and between group difference are Least Squares Mean (Standard Error) from the model adjusted for baseline six-minute walk + age + sex + race + resveratrol usage.
Time frame: Baseline to 6-month follow-up
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide Riboside + Resveratrol | Six-minute Walk Distance (NR/Resveratrol or NR Alone vs. Placebo) | -14.29 meters | Standard Error 9.97 |
| Nicotinamide Riboside + Placebo | Six-minute Walk Distance (NR/Resveratrol or NR Alone vs. Placebo) | -0.24 meters | Standard Error 5.81 |
Comparison: Mixed models for repeated measures were used to compare 6-month change in 6MW distance between the NR/resveratrol vs placebo groups and between the NR alone vs placebo groups using baseline, 3-month, and 6-month values, adjusted for age, sex, race, and baseline 6MW.p-value: 0.1195Mixed Models Analysis
Secondary
Six-minute Walk Distance (NR/Resveratrol vs. NR Alone)
Among participants with PAD, investigators will determine whether NR combined with resveratrol improves six-minute walk performance at 6-month follow-up, compared to NR alone.
Time frame: Baseline to 6-month follow-up
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide Riboside + Resveratrol | Six-minute Walk Distance (NR/Resveratrol vs. NR Alone) | -6.93 meters | Standard Error 7.84 |
| Nicotinamide Riboside + Placebo | Six-minute Walk Distance (NR/Resveratrol vs. NR Alone) | 7.00 meters | Standard Error 8.69 |
| Placebo + Placebo | Six-minute Walk Distance (NR/Resveratrol vs. NR Alone) | -10.58 meters | Standard Error 8.45 |
p-value: 0.8797Mixed Models Analysis
Secondary
Six-minute Walk Distance (NR/Resveratrol vs. NR Alone)
Among participants with PAD, investigators will determine whether NR combined with resveratrol improves six-minute walk performance at 3-month follow-up, compared to NR alone.
Time frame: Baseline to 3-month follow-up
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide Riboside + Resveratrol | Six-minute Walk Distance (NR/Resveratrol vs. NR Alone) | 2.99 meters | Standard Error 7.67 |
| Nicotinamide Riboside + Placebo | Six-minute Walk Distance (NR/Resveratrol vs. NR Alone) | 4.78 meters | Standard Error 8.28 |
| Placebo + Placebo | Six-minute Walk Distance (NR/Resveratrol vs. NR Alone) | -17.64 meters | Standard Error 8.03 |
p-value: 0.562Mixed Models Analysis
Secondary
Six-minute Walk Distance (NR/Resveratrol vs. Placebo)
Among participants with PAD, investigators will determine whether NR combined with resveratrol improves six-minute walk performance at 3-month follow-up, compared to placebo.
Time frame: Baseline to 3-month follow-up
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide Riboside + Resveratrol | Six-minute Walk Distance (NR/Resveratrol vs. Placebo) | 2.99 meters | Standard Error 7.67 |
| Nicotinamide Riboside + Placebo | Six-minute Walk Distance (NR/Resveratrol vs. Placebo) | 4.78 meters | Standard Error 8.28 |
| Placebo + Placebo | Six-minute Walk Distance (NR/Resveratrol vs. Placebo) | -17.64 meters | Standard Error 8.03 |
p-value: 0.0336Mixed Models Analysis
Secondary
Walking Impairment Questionnaire (WIQ) Distance Score (NR Alone vs. Placebo)
Among participants with PAD, investigators will determine whether NR alone improves the Walking Impairment Questionnaire (WIQ) distance score at 6-month follow-up, compared to placebo. The WIQ is a well validated questionnaire that measures patient-reported walking limitations in distance and speed and stair-climbing. They are scored on a 0-100 scale and that 100 indicates the best possible score.
Time frame: Baseline to 6-month follow-up
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide Riboside + Resveratrol | Walking Impairment Questionnaire (WIQ) Distance Score (NR Alone vs. Placebo) | 0.82 score on a scale | Standard Error 3.96 |
| Nicotinamide Riboside + Placebo | Walking Impairment Questionnaire (WIQ) Distance Score (NR Alone vs. Placebo) | -1.24 score on a scale | Standard Error 4.42 |
| Placebo + Placebo | Walking Impairment Questionnaire (WIQ) Distance Score (NR Alone vs. Placebo) | 5.86 score on a scale | Standard Error 4.31 |
p-value: 0.8703ANCOVA
Secondary
Walking Impairment Questionnaire (WIQ) Distance Score (NR/Resveratrol or NR Alone vs. Placebo)
Participants with PAD who received NR alone and those who received NR + resveratrol will be combined into one group and compared to the group receiving placebo, to determine whether NR alone or NR+ resveratrol (combined group)have greater improvement in Walking Impairment Questionnaire distance score, compared to those randomized to placebo. The WIQ is a well validated questionnaire that measures patient-reported walking limitations in distance and speed and stair-climbing. They are scored on a 0-100 scale and that 100 indicates the best possible score.
Time frame: Baseline to 6-month follow-up
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide Riboside + Resveratrol | Walking Impairment Questionnaire (WIQ) Distance Score (NR/Resveratrol or NR Alone vs. Placebo) | 6.89 score on a scale | Standard Error 5.29 |
| Nicotinamide Riboside + Placebo | Walking Impairment Questionnaire (WIQ) Distance Score (NR/Resveratrol or NR Alone vs. Placebo) | -0.21 score on a scale | Standard Error 2.94 |
Comparison: Mixed model for repeated measures is applied to Placebo vs. 2 NR groups combined. The reported results of within group change and between group difference are Least Squares Mean (Standard Error) from the model adjusted for baseline six-minute walk + age + sex + race + resveratrol usage.p-value: 0.8703ANCOVA
Secondary
Walking Impairment Questionnaire (WIQ) Distance Score (NR/Resveratrol vs. NR Alone)
Among participants with PAD, investigators will determine whether NR combined with resveratrol improves the Walking Impairment Questionnaire (WIQ) distance score at 6-month follow-up, compared to NR alone. The WIQ is a well validated questionnaire that measures patient-reported walking limitations in distance and speed and stair-climbing. They are scored on a 0-100 scale and that 100 indicates the best possible score.
Time frame: Baseline to 6-month follow-up
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide Riboside + Resveratrol | Walking Impairment Questionnaire (WIQ) Distance Score (NR/Resveratrol vs. NR Alone) | 0.82 score on a scale | Standard Error 3.96 |
| Nicotinamide Riboside + Placebo | Walking Impairment Questionnaire (WIQ) Distance Score (NR/Resveratrol vs. NR Alone) | -1.24 score on a scale | Standard Error 4.42 |
| Placebo + Placebo | Walking Impairment Questionnaire (WIQ) Distance Score (NR/Resveratrol vs. NR Alone) | 5.86 score on a scale | Standard Error 4.31 |
p-value: 0.3662ANCOVA
Secondary
Walking Impairment Questionnaire (WIQ) Distance Score (NR/Resveratrol vs. Placebo)
Among participants with PAD, investigators will determine whether NR combined with resveratrol improves the Walking Impairment Questionnaire distance score at 6-month follow-up, compared to placebo. The WIQ is a well validated questionnaire that measures patient-reported walking limitations in distance and speed and stair-climbing. They are scored on a 0-100 scale and that 100 indicates the best possible score.
Time frame: Baseline to 6-month follow-up
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide Riboside + Resveratrol | Walking Impairment Questionnaire (WIQ) Distance Score (NR/Resveratrol vs. Placebo) | 0.82 score on a scale | Standard Error 3.96 |
| Nicotinamide Riboside + Placebo | Walking Impairment Questionnaire (WIQ) Distance Score (NR/Resveratrol vs. Placebo) | -1.24 score on a scale | Standard Error 4.42 |
| Placebo + Placebo | Walking Impairment Questionnaire (WIQ) Distance Score (NR/Resveratrol vs. Placebo) | 5.86 score on a scale | Standard Error 4.31 |
p-value: 0.8039ANCOVA
Other Pre-specified
Gastrocnemius Muscle Satellite Cell Abundance (NR/Resveratrol vs. Placebo and NR vs. Placebo)
Investigators will perform calf muscle biopsies to determine whether among participants with PAD, those randomized to NR + resveratrol and NR alone have increased satellite cell abundance compared to the placebo group. Satellite cell abundance was measured via density (satellite cells/100 fibers) using antibodies against: Pax7, type 1 myosin, and laminin.
Time frame: Baseline to 6-month follow-up
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide Riboside + Resveratrol | Gastrocnemius Muscle Satellite Cell Abundance (NR/Resveratrol vs. Placebo and NR vs. Placebo) | -3.36 satellite cells/100 fibers | Standard Error 4.33 |
| Nicotinamide Riboside + Placebo | Gastrocnemius Muscle Satellite Cell Abundance (NR/Resveratrol vs. Placebo and NR vs. Placebo) | 1.73 satellite cells/100 fibers | Standard Error 4.52 |
| Placebo + Placebo | Gastrocnemius Muscle Satellite Cell Abundance (NR/Resveratrol vs. Placebo and NR vs. Placebo) | -9.41 satellite cells/100 fibers | Standard Error 3.8 |
Comparison: Mixed model for repeated measures is applied to 3 groups comparisons. The reported results of within group change and between group difference are Least Squares Mean (Standard Error) from the model adjusted for baseline six-minute walk + age + sex + race + resveratrol usage.p-value: 0.1589ANCOVA
Comparison: Mixed model for repeated measures is applied to 3 groups comparisons. The reported results of within group change and between group difference are Least Squares Mean (Standard Error) from the model adjusted for baseline six-minute walk + age + sex + race + resveratrol usage.p-value: 0.0602ANCOVA
Other Pre-specified
Muscle Fiber Phenotype in Gastrocnemius Muscle (NR/Resveratrol vs. Placebo and NR vs. Placebo)
Investigators will perform calf muscle biopsies to determine whether among participants with PAD, those randomized to NR + resveratrol and NR alone have improved muscle fiber phenotype (Percent Type 1 myofibers (%)), compared to the placebo group. Measurements of fiber type % were determined on frozen muscle sections using antibodies against: Pax7, type 1 myosin, and laminin.
Time frame: Baseline to 6-month follow-up
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide Riboside + Resveratrol | Muscle Fiber Phenotype in Gastrocnemius Muscle (NR/Resveratrol vs. Placebo and NR vs. Placebo) | -5.94 percentage | Standard Error 4.88 |
| Nicotinamide Riboside + Placebo | Muscle Fiber Phenotype in Gastrocnemius Muscle (NR/Resveratrol vs. Placebo and NR vs. Placebo) | 0.17 percentage | Standard Error 4.86 |
| Placebo + Placebo | Muscle Fiber Phenotype in Gastrocnemius Muscle (NR/Resveratrol vs. Placebo and NR vs. Placebo) | -5.04 percentage | Standard Error 4.12 |
Comparison: Mixed model for repeated measures is applied to 3 groups comparisons. The reported results of within group change and between group difference are Least Squares Mean (Standard Error) from the model adjusted for baseline six-minute walk + age + sex + race + resveratrol usage.p-value: 0.5558ANCOVA
Comparison: Mixed model for repeated measures is applied to 3 groups comparisons. The reported results of within group change and between group difference are Least Squares Mean (Standard Error) from the model adjusted for baseline six-minute walk + age + sex + race + resveratrol usage.p-value: 0.2378ANCOVA
Other Pre-specified
NAD+ Abundance in Gastrocnemius Muscle (NR/Resveratrol vs. Placebo and NR vs. Placebo)
Investigators will perform calf muscle biopsies to determine whether among participants with PAD, those randomized to NR + resveratrol and NR alone have increased calf muscle NAD+ abundance, compared to the placebo group. Measurements of NAD+ abundance were completed using High Performance Liquid Chromatography (HPLC) with a Shimadzu LC-20A pump and UV-VIS detector using a Supelco LC-18-Tcolumn, normalized to muscle weight.
Time frame: Baseline to 6-month follow-up
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide Riboside + Resveratrol | NAD+ Abundance in Gastrocnemius Muscle (NR/Resveratrol vs. Placebo and NR vs. Placebo) | 31.39 pmol/mg | Standard Error 22.57 |
| Nicotinamide Riboside + Placebo | NAD+ Abundance in Gastrocnemius Muscle (NR/Resveratrol vs. Placebo and NR vs. Placebo) | -13.99 pmol/mg | Standard Error 23.44 |
| Placebo + Placebo | NAD+ Abundance in Gastrocnemius Muscle (NR/Resveratrol vs. Placebo and NR vs. Placebo) | 21.14 pmol/mg | Standard Error 20.03 |
Comparison: Mixed model for repeated measures is applied to 3 groups comparisons. The reported results of within group change and between group difference are Least Squares Mean (Standard Error) from the model adjusted for baseline six-minute walk + age + sex + race + resveratrol usage.p-value: 0.3724ANCOVA
Comparison: Mixed model for repeated measures is applied to 3 groups comparisons. The reported results of within group change and between group difference are Least Squares Mean (Standard Error) from the model adjusted for baseline six-minute walk + age + sex + race + resveratrol usage.p-value: 0.8401ANCOVA
Other Pre-specified
Short-Form Physical Functioning (SF-36) Score (NR Alone vs. Placebo)
Among participants with PAD, investigators will determine whether NR alone improves the Walking Impairment Questionnaire speed and stair climbing scores and the Short-Form Physical Functioning score at 6-month follow-up, compared to placebo. The SF-36 measures health status. The score range is 0-100, where 100 is best.
Time frame: Baseline to 6-month follow-up
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide Riboside + Resveratrol | Short-Form Physical Functioning (SF-36) Score (NR Alone vs. Placebo) | 0.65 score on a scale | Standard Error 2.89 |
| Nicotinamide Riboside + Placebo | Short-Form Physical Functioning (SF-36) Score (NR Alone vs. Placebo) | -3.40 score on a scale | Standard Error 3.23 |
| Placebo + Placebo | Short-Form Physical Functioning (SF-36) Score (NR Alone vs. Placebo) | 4.00 score on a scale | Standard Error 3.15 |
p-value: 0.9449ANCOVA
Other Pre-specified
Short-Form Physical Functioning (SF-36) Score (NR/Resveratrol or NR Alone vs. Placebo)
Participants with PAD who received NR alone and those who received NR + resveratrol will be combined into one group and compared to the group receiving placebo, to determine whether NR alone or NR+ resveratrol (combined group) have greater improvement in the Short-Form Physical Functioning score at 6-month follow-up, compared to placebo. The SF-36 measures health status. The score range is 0-100, where 100 is best.
Time frame: Baseline to 6-month follow-up
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide Riboside + Resveratrol | Short-Form Physical Functioning (SF-36) Score (NR/Resveratrol or NR Alone vs. Placebo) | 6.02 score on a scale | Standard Error 3.87 |
| Nicotinamide Riboside + Placebo | Short-Form Physical Functioning (SF-36) Score (NR/Resveratrol or NR Alone vs. Placebo) | -1.37 score on a scale | Standard Error 2.15 |
Comparison: Mixed model for repeated measures is applied to Placebo vs. 2 NR groups combined. The reported results of within group change and between group difference are Least Squares Mean (Standard Error) from the model adjusted for baseline six-minute walk + age + sex + race + resveratrol usage.p-value: 0.9449ANCOVA
Other Pre-specified
Short-Form Physical Functioning (SF-36) Score (NR/Resveratrol vs. NR Alone)
Among participants with PAD, investigators will determine whether NR combined with resveratrol improves the Walking Impairment Questionnaire speed and stair climbing scores and the Short-Form Physical Functioning score at 6-month follow-up, compared to NR alone. The SF-36 measures health status. The score range is 0-100, where 100 is best.
Time frame: Baseline to 6-month follow-up
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide Riboside + Resveratrol | Short-Form Physical Functioning (SF-36) Score (NR/Resveratrol vs. NR Alone) | 0.65 score on a scale | Standard Error 2.89 |
| Nicotinamide Riboside + Placebo | Short-Form Physical Functioning (SF-36) Score (NR/Resveratrol vs. NR Alone) | -3.40 score on a scale | Standard Error 3.23 |
| Placebo + Placebo | Short-Form Physical Functioning (SF-36) Score (NR/Resveratrol vs. NR Alone) | 4.00 score on a scale | Standard Error 3.15 |
p-value: 0.1787ANCOVA
Other Pre-specified
Short-Form Physical Functioning (SF-36) Score (NR/Resveratrol vs. Placebo)
Among participants with PAD, investigators will determine whether NR combined with resveratrol improves the Short-Form Physical Functioning score at 6-month follow-up, compared to placebo. The SF-36 measures health status. The score range is 0-100, where 100 is best.
Time frame: Baseline to 6-month follow-up
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide Riboside + Resveratrol | Short-Form Physical Functioning (SF-36) Score (NR/Resveratrol vs. Placebo) | 0.65 score on a scale | Standard Error 2.89 |
| Nicotinamide Riboside + Placebo | Short-Form Physical Functioning (SF-36) Score (NR/Resveratrol vs. Placebo) | -3.40 score on a scale | Standard Error 3.23 |
| Placebo + Placebo | Short-Form Physical Functioning (SF-36) Score (NR/Resveratrol vs. Placebo) | 4.00 score on a scale | Standard Error 3.15 |
p-value: 0.7814ANCOVA
Other Pre-specified
Walking Impairment Questionnaire (WIQ) Speed Score (NR Alone vs. Placebo)
Among participants with PAD, investigators will determine whether NR alone improves the Walking Impairment Questionnaire speed and stair climbing score at 6-month follow-up, compared to placebo. The WIQ is a well validated questionnaire that measures patient-reported walking limitations in distance and speed and stair-climbing. They are scored on a 0-100 scale and that 100 indicates the best possible score.
Time frame: Baseline to 6-month follow-up
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide Riboside + Resveratrol | Walking Impairment Questionnaire (WIQ) Speed Score (NR Alone vs. Placebo) | -0.82 score on a scale | Standard Error 3.08 |
| Nicotinamide Riboside + Placebo | Walking Impairment Questionnaire (WIQ) Speed Score (NR Alone vs. Placebo) | 0.22 score on a scale | Standard Error 3.43 |
| Placebo + Placebo | Walking Impairment Questionnaire (WIQ) Speed Score (NR Alone vs. Placebo) | 2.93 score on a scale | Standard Error 3.34 |
p-value: 0.7112ANCOVA
Other Pre-specified
Walking Impairment Questionnaire (WIQ) Speed Score (NR/Resveratrol or NR Alone vs. Placebo)
Participants with PAD who received NR alone and those who received NR + resveratrol will be combined into one group and compared to the group receiving placebo, to determine whether NR alone or NR+ resveratrol (combined group) have greater improvement in the Walking Impairment Questionnaire (WIQ) speed and stair climbing score at 6-month follow-up, compared to placebo. The WIQ is a well validated questionnaire that measures patient-reported walking limitations in distance and speed and stair-climbing. They are scored on a 0-100 scale and that 100 indicates the best possible score.
Time frame: Baseline to 6-month follow-up
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide Riboside + Resveratrol | Walking Impairment Questionnaire (WIQ) Speed Score (NR/Resveratrol or NR Alone vs. Placebo) | 2.41 score on a scale | Standard Error 4.1 |
| Nicotinamide Riboside + Placebo | Walking Impairment Questionnaire (WIQ) Speed Score (NR/Resveratrol or NR Alone vs. Placebo) | -0.30 score on a scale | Standard Error 2.28 |
Comparison: Mixed model for repeated measures is applied to Placebo vs. 2 NR groups combined. The reported results of within group change and between group difference are Least Squares Mean (Standard Error) from the model adjusted for baseline six-minute walk + age + sex + race + resveratrol usage.p-value: 0.7112ANCOVA
Other Pre-specified
Walking Impairment Questionnaire (WIQ) Speed Score (NR/Resveratrol vs. NR Alone)
Among participants with PAD, investigators will determine whether NR combined with resveratrol improves the Walking Impairment Questionnaire speed and stair climbing score at 6-month follow-up, compared to NR alone. The WIQ is a well validated questionnaire that measures patient-reported walking limitations in distance and speed and stair-climbing. They are scored on a 0-100 scale and that 100 indicates the best possible score.
Time frame: Baseline to 6-month follow-up
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide Riboside + Resveratrol | Walking Impairment Questionnaire (WIQ) Speed Score (NR/Resveratrol vs. NR Alone) | -0.82 score on a scale | Standard Error 3.08 |
| Nicotinamide Riboside + Placebo | Walking Impairment Questionnaire (WIQ) Speed Score (NR/Resveratrol vs. NR Alone) | 0.22 score on a scale | Standard Error 3.43 |
| Placebo + Placebo | Walking Impairment Questionnaire (WIQ) Speed Score (NR/Resveratrol vs. NR Alone) | 2.93 score on a scale | Standard Error 3.34 |
p-value: 0.5884ANCOVA
Other Pre-specified
Walking Impairment Questionnaire (WIQ) Stair Climbing Score (NR/Resveratrol vs. Placebo)
Among participants with PAD, investigators will determine whether NR combined with resveratrol improves the Walking Impairment Questionnaire speed and stair climbing scores at 6-month follow-up, compared to placebo. The WIQ is a well validated questionnaire that measures patient-reported walking limitations in distance and speed and stair-climbing. They are scored on a 0-100 scale and that 100 indicates the best possible score.
Time frame: Baseline to 6-month follow-up
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide Riboside + Resveratrol | Walking Impairment Questionnaire (WIQ) Stair Climbing Score (NR/Resveratrol vs. Placebo) | -2.64 score on a scale | Standard Error 3.18 |
| Nicotinamide Riboside + Placebo | Walking Impairment Questionnaire (WIQ) Stair Climbing Score (NR/Resveratrol vs. Placebo) | 2.09 score on a scale | Standard Error 3.55 |
| Placebo + Placebo | Walking Impairment Questionnaire (WIQ) Stair Climbing Score (NR/Resveratrol vs. Placebo) | -2.15 score on a scale | Standard Error 3.46 |
p-value: 0.5409ANCOVA