Clinical trial NCT02246660
Conditions: Peripheral Arterial Disease
Keywords: Peripheral Artery Disease Peripheral Arterial Disease PAD
Sponsor: Northwestern University
Start date: 2015-01-01; Completion date: 2016-09-01
Enrollment: 66 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The RESTORE trial will determine whether resveratrol supplementation can improve walking performance in older people with lower extremity peripheral arterial disease (PAD). Resveratrol, a polyphenol and natural supplement, specifically targets several impairments associated with walking difficulty and mobility loss in people with PAD.

Detailed description:
Eight million men and women in the United States have lower extremity peripheral arterial disease (PAD). PAD is expected to be increasingly common as the population survives longer with chronic disease. Patients with PAD have greater functional impairment and faster functional decline compared to those without PAD. However, currently there are only two FDA approved medications for improving functional performance in patients with PAD. Furthermore, these FDA approved medications are only modestly beneficial for improving walking performance in patients with PAD.

Emerging evidence, including our pilot data, demonstrates that calf skeletal muscle mitochondria dysfunction contributes to functional impairment in people with PAD. Resveratrol, a polyphenol and natural supplement, has pharmacological properties that target specific mitochondrial impairments that are associated with functional impairment in older people with PAD. Animal models and preliminary human evidence show that resveratrol protects against ischemia-reperfusion injury, reduces inflammation, and improves endothelial dysfunction. Ischemia-reperfusion injury, inflammation, and endothelial dysfunction are all present in people with PAD and contribute to adverse outcomes in PAD.

We now propose a pilot study of 66 PAD participants age 65 and older: a double-blind, randomized controlled pilot clinical trial to provide preliminary data to address our hypothesis that resveratrol significantly improves lower extremity functioning in people with PAD by improving calf skeletal muscle oxidative metabolism, increasing calf skeletal muscle mitochondrial biogenesis, and improving systemic endothelial function in older people with PAD.

In our primary specific aims, we will determine 1) whether PAD participants randomized to resveratrol 500 mgs daily achieve greater increases or have less decline in six-minute walk performance at 6-month follow-up, compared to those randomized to placebo and 2) whether PAD participants randomized to resveratrol 125 mgs daily achieve greater increases or have less decline in six-minute walk performance at 6-month follow-up, compared to those randomized to placebo. In our secondary aims, we will determine whether PAD participants randomized to resveratrol have improved treadmill walking performance, increased calf muscle biopsy-measured mitochondrial function, increased calf muscle biopsy-measured mitochondrial biogenesis, and improved brachial artery flow-mediated dilation at six-month follow-up, compared to those randomized to control. For each secondary specific aim, participants randomized to 500 mgs of resveratrol (N=22) will be compared to those randomized to placebo (N=20) and participants randomized to 125 mgs of resveratrol (N=22) will be compared to those randomized to placebo (N=22), respectively. In an exploratory specific aim, we will determine whether participants randomized to resveratrol 125 mgs (N=22) have greater improvement in each study outcome compared to those randomized to resveratrol 500 mgs (N=22).

If our hypotheses are correct, results will be used to design a large, definitive randomized controlled trial of resveratrol therapy to improve lower extremity functioning and prevent mobility loss in the large and growing number of older people who are disabled by PAD. By studying two doses of resveratrol, our results will also provide guidance on the most optimal dose of resveratrol to use in a large definitive trial.

Arms: arm 1: The dose of Resveratrol will be 500 mg daily for six months. Resveratrol is taken orally. Resveratrol is a natural plant derivative. arm 2: The dose of Resveratrol will be 125 mg daily for six months. Resveratrol is taken orally. Resveratrol is a natural plant derivative. arm 3: Placebo will be taken orally for 6 months.
Interventions: intervention 1: Resveratrol intervention 2: Placebo
Intervention descriptions: intervention 1: The dose of Resveratrol will be 500 mg daily for six months. Resveratrol is taken orally. Resveratrol is a natural plant derivative.

OR

The dose of Resveratrol will be 125 mg daily for six months. Resveratrol is taken orally. Resveratrol is a natural plant derivative. intervention 2: Placebo will be taken orally for 6 months.

Protocol documents: