Unacylated Ghrelin to Improve Functioning in PAD

NCT04377126 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: STU00209681R21AG063076
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 2

Brief 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

Conditions

Peripheral Artery Disease

Keywords

Unacylated ghrelin

Outcome Measures

Primary Outcomes (1)

• 4-month change in six-minute walk distance

  Change in six minute walk distance at 4-month follow-up will be compared between those randomized to subcutaneously administered unacylated ghrelin vs. those randomized to placebo.

  Baseline to 4 months

Secondary Outcomes (2)

• 4-month change in maximal treadmill walking time

  Baseline to 4 months

• 4-month change in calf muscle perfusion

  Baseline to 4 months

Other Outcomes (6)

• 4-month change in calf muscle fiber type and size

  Baseline to 4 months

• 4-month change in satellite cell number

  Baseline to 4 months

• 4-month change in capillary density (capillaries per muscle fiber)

  Baseline to 4 months

Study Arms (2)

Unacylated ghrelin

ACTIVE COMPARATOR

Participants randomized to unacylated ghrelin will self-administer 20 ug/kg unacylated ghrelin daily. Study drug is dispensed in syringes labeled with the participant's name, date of birth, expiration date, and instructions for administration. Syringes will NOT be labeled with the group assignment, ensuring that both the research team collecting data and study participants are blinded to group assignment (i.e. double blinded status). Study drug is stored and handled according to the University of Chicago Research Pharmacy Standard Operating Procedure (SOP).

Drug: Ghrelin

Placebo

PLACEBO COMPARATOR

Participants randomized to placebo will self-administer an identical-appearing solution of bacteriostatic saline daily.

Drug: Placebo

Interventions

Ghrelin DRUG

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.

Also known as: Unacylated ghrelin

Unacylated ghrelin

Placebo DRUG

Placebo will consist of saline- no active ingredient.

Also known as: Inactive substance

Placebo

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years and older
• Presence of peripheral artery disease defined as either:
• An ankle-brachial index (ABI) of less than or equal to 0.90 at the baseline study visit
• Vascular lab evidence of PAD or angiographic evidence of PAD with ischemic leg symptoms during the six-minute walk and/or treadmill exercise stress test.

You may not qualify if:

• Above- or below-knee amputation.
• Critical limb ischemia.
• Wheelchair-bound or requiring a cane or walker to ambulate.
• Walking is limited by a symptom other than PAD.
• Current ulcer on bottom of foot. The participant may become eligible after the ulcer heals.
• Significant liver or kidney impairment defined as two or more hepatic function enzymes \> 3.0 times the upper limit of normal and/or eGFR \< 20. \[NOTE: participants who meet this criterion may undergo a re-test of hepatic function tests to determine whether initially elevated hepatic enzymes represented a transient or spurious phenomenon.\]
• Unwilling or unable to self-administer study drug.
• Failure to successfully complete the study run-in.
• Planned lower extremity revascularization or other major surgery during the next four months.
• Lower extremity revascularization, major orthopedic surgery, cardiovascular event, coronary revascularization, or other major surgery in the previous three months.
• 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. \[NOTE: potential participants may still qualify if they have had treatment for an early stage cancer in the past two years and the prognosis is excellent. Participants who only use oxygen at night may still qualify.\]
• Mini-Mental Status Examination (MMSE) score \< 23
• Participation in or completion of a clinical trial in the previous three months. \[NOTE: after completing a stem cell or gene therapy intervention, participants will become eligible after the final study follow-up visit of the stem cell or gene therapy study so long as at least six months have passed since the final intervention administration. After completing a supplement or drug therapy (other than stem cell or gene therapy), participants will be eligible after the final study follow-up visit as long as at least three months have passed since the final intervention of the trial.\]
• Currently taking study drug(s) or has taken study drug(s) in past six months.
• Increase in angina in last month or angina at rest.

Sponsors & Collaborators

• Northwestern University: lead
• National Institute on Aging (NIA): collaborator

Study Sites (2)

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611-3008, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Related Publications (1)

• Nayak P, Polonsky T, Tian L, Greenland P, Xu S, Zhang D, Zhao L, Criqui MH, Kibbe MR, Gladders B, Goodney P, Ho K, Guralnik JM, McDermott MM. Medical therapies, comorbid conditions, and functional performance in people with peripheral artery disease enrolled in clinical trials between 2004 and 2021. Vasc Med. 2023 Apr;28(2):144-146. doi: 10.1177/1358863X221145533. Epub 2023 Jan 1.

  PMID: 36588397 DERIVED

MeSH Terms

Conditions

Peripheral Arterial Disease

Interventions

Ghrelin

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases

Intervention Hierarchy (Ancestors)

Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Mary McDermott, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Both the research team collecting data and study participants will be blinded to group assignment (i.e. double blinded status).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Jeremiah Stamler Professor of Medicine

Model Details: Participants will be randomized to subcutaneously administered unacylated ghrelin or placebo.

Study Record Dates

• First Submitted: May 4, 2020
• First Posted: May 6, 2020
• Study Start: July 8, 2020
• Primary Completion: January 23, 2025
• Study Completion: January 23, 2025
• Last Updated: April 29, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)