Trial Outcomes & Findings for Nicotinamide Riboside With and Without Resveratrol to Improve Functioning in Peripheral Artery Disease (NCT NCT03743636)

Nicotinamide Riboside With and Without Resveratrol to Improve Functioning in Peripheral Artery Disease

Among participants with PAD, investigators will determine whether NR alone improves six-minute walk distance at 6-month follow-up, compared to 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.

Among participants with PAD, investigators will determine whether NR alone improves six-minute walk performance at 3-month follow-up, compared to 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.

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.

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.

Among participants with PAD, investigators will determine whether NR alone improves maximal treadmill walking time at 6-month follow-up, compared to 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.