NCT04377126

Unacylated Ghrelin to Improve Functioning in PAD

Unacylated Ghrelin to Improve Functioning in PAD: The GIFT Trial Phase II

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 25 (actual)
• Sponsor: Northwestern University · Academic / Other
• Sex: All
• Age: 55 Years
• Healthy volunteers: Accepted

Summary

GIFT is a pilot, randomized, double-blinded clinical trial that will examine the effects of unacylated ghrelin on walking ability in people with peripheral artery disease (PAD) compared to placebo. Preliminary evidence suggests that unacylated ghrelin may improve blood flow to the extremities and promote improved skeletal muscle growth and energy use. A total of 30 participants with PAD will be randomized to one of two groups: unacylated ghrelin injections or placebo injections . Participants will self-administer the study drug or placebo subcutaneously once daily for four months. The primary outcome is change in six-minute walk distance between baseline and 4-month follow-up

Detailed description

Work from the McDermott research team and that of other investigators shows that patients with lower extremity peripheral artery disease (PAD) have greater functional impairment, faster functional decline, and higher rates of mobility loss compared to people without PAD. In patients with PAD, ischemia results in calf muscle injury that includes myofiber loss and calf muscle mitochondrial dysfunction. Therapies to regenerate calf skeletal muscle cells, improve mitochondrial function, and increase calf muscle capillary density may improve functioning and prevent mobility loss in people with PAD. Yet few effective therapies currently exist for patients with PAD. This pilot study will investigate the therapeutic potential of unacylated ghrelin to promote capillary growth, increase calf muscle perfusion, and reverse PAD-related skeletal muscle abnormalities, thereby improving PAD-related functional impairment. Ghrelin is a peptide and hormone that circulates in acylated and unacylated forms. Unacylated ghrelin promotes skeletal muscle cell regeneration, improves mitochondrial function, and increases muscle capillary density. Unlike acylated ghrelin, unacylated ghrelin does not increase appetite, or cause insulin resistance. The proposed GIFT Trial will provide preliminary data to test the hypothesis that unacylated ghrelin improves walking performance and prevents mobility loss in older patients with PAD. Furthermore, the investigators hypothesize that the favorable effect of unacylated ghrelin will be mediated by increased myofiber regeneration, increased muscle capillary density, and improved muscle mitochondria function. If preliminary data support these hypotheses, results will be used to design a large randomized trial of unacylated ghrelin therapy, in subsequent study, to improve functioning and prevent mobility loss in older people with PAD. Investigators will conduct a pilot randomized trial in 30 participants age 55 and older with PAD, to gather preliminary evidence about whether daily subcutaneously administered unacylated improves the six-minute walk distance (primary outcome), maximal treadmill walking time(secondary outcome), and calf muscle perfusion (secondary outcome), compared to placebo. Investigators will also perform calf muscle biopsies at baseline and follow up to determine whether unacylated ghrelin increases Type 1 skeletal muscle myofibers, satellite cell number, capillary density, and succinate dehydrogenase (SDH) mitochondrial activity in calf skeletal muscle, compared to placebo. If these hypotheses are correct, results will be used to design a large, definitive randomized trial of unacylated ghrelin to improve lower extremity functioning and prevent mobility loss in the large and growing number of older people who are disabled by PAD.

Conditions

• Peripheral Artery Disease

Interventions

Type	Name	Description
DRUG	Ghrelin	Ghrelin is a peptide and hormone that is primarily produced by P/D1 cells of the gastric fundus and circulates in both acylated and unacylated forms. This pilot trial will gather preliminary evidence to test investigators hypothesis that unacylated ghrelin improves walking performance and prevents mobility loss in older patients with PAD.
DRUG	Placebo	Placebo will consist of saline- no active ingredient.

Timeline

• Start date: 2020-07-08
• Primary completion: 2025-01-23
• Completion: 2025-01-23
• First posted: 2020-05-06
• Last updated: 2025-04-29

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study