Peripheral Artery DiseasePhase 2GIFTIINCT04377126
Unacylated Ghrelin to Improve Functioning in PAD
A Phase 2 study testing Ghrelin in people with Peripheral Artery Disease, run by Northwestern University at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 55 years and olderHealthy volunteers can take part
- Conditions the study is for
- Peripheral Artery Disease
- What is being tested?
- Ghrelin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- 2 sitesUnited States
- Study dates
- 8 Jul 2020to 23 Jan 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 55 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.
Who cannot join
- 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.]
Show all 22Show fewer
- 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.
- Non-English speaking.
- Visual impairment that limits walking ability.
- Women who are pregnant or who are pre-menopausal will not be eligible.
- Potential participants who recently participated in or are currently participating in a supervised treadmill exercise and those planning to begin a supervised treadmill exercise regimen will become eligible four months after their participation in the supervised treadmill exercise program has ended.
- 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.
- The potential participant does not have adequate refrigeration for storing study drug.
- Vulnerable populations (fetuses, pregnant women, children, prisoners, and institutionalized persons) and adults unable to consent will not be included in the study.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Northwestern University Feinberg School of Medicine
Chicago, Illinois, 60611-3008
University of Chicago
Chicago, Illinois, 60637
About this study
Official title: Unacylated Ghrelin to Improve Functioning in PAD: The GIFT Trial Phase II
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
Read the 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
- Being tested
- Ghrelin, Placebo
- Keywords
- Unacylated ghrelin
- Medical subject headings
- Peripheral Arterial Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GhrelinDrug
Also called Unacylated 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.
PlaceboDrug
Also called Inactive substance
Placebo will consist of saline- no active ingredient.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Drug: Ghrelin |
| Placebo | Placebo comparator | Participants randomized to placebo will self-administer an identical-appearing solution of bacteriostatic saline daily. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to 4 months
Secondary outcomes (2)
4-month Change in Maximal Treadmill Walking Time
Change in maximal treadmill walking time at 4 month follow-up will be compared between those randomized to subcutaneously administered unacylated ghrelin vs. those randomized to placebo.
Measured: Baseline to 4 months
4-month Change in Calf Muscle Perfusion
Perfusion was measured using cuff occlusion hyperemia while the participant was supine. The cuff occlusion hyperemia MRI was performed by inflating a thigh cuff to 250 mm Hg in the leg with lowest ABI for five minutes while the participant was supine. After five minutes, the cuff was rapidly deflated. Seven control-tagged image pairs were acquired over 60 seconds using PASL pulse sequence with single-shot echo-planar imaging readouts. Images were interpreted using a Siemens Healthcare workstation.
Measured: Baseline to 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2020
- Study start8 Jul 2020
- Primary completion23 Jan 2025
- Study completion23 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Peripheral Artery DiseaseStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomized to subcutaneously administered unacylated ghrelin or placebo.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Principal investigator, Mary McDermott, Northwestern University
- Investigators
- Mary McDermott, MD, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04377126
- Sponsor's protocol ID
- STU00209681
- Other IDs
- R21AG063076
- Acronym
- GIFTII
- Status last verified
- Apr 2026
- First submitted
- 4 May 2020
- Last updated
- 1 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 36588397
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Unacylated Ghrelin to Improve Functioning in PAD: The GIFT Trial Phase II
- ClinicalTrials.gov ID
- NCT04377126
- Acronym / sponsor ID
- GIFTII / STU00209681
- Conditions
- Peripheral Artery Disease
- Keywords
- Unacylated ghrelin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 8 Jul 2020 (actual)
- Primary completion
- 23 Jan 2025 (actual)
- Study completion
- 23 Jan 2025 (actual)
- First posted
- 6 May 2020 (actual)
- Results
- Posted 1 Jun 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- Participants will be randomized to subcutaneously administered unacylated ghrelin or placebo.
| Arm | Type | Receives |
|---|---|---|
| Unacylated ghrelin | Active comparator | Drug: GhrelinParticipants 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). |
| Placebo | Placebo comparator | Drug: PlaceboParticipants randomized to placebo will self-administer an identical-appearing solution of bacteriostatic saline daily. |
Who may qualify
- Ages
- 55 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 55 years and older
- Presence of peripheral artery disease defined as either:
Key exclusion criteria (22 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GhrelinAlso: Unacylated ghrelinGhrelin 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 | Unacylated ghrelin |
| PlaceboAlso: Inactive substancePlacebo will consist of saline- no active ingredient. | Drug | Placebo |
Primary outcome
4-month Change in Six-minute Walk Distance
Time frame: Baseline to 4 months
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.
2 secondary outcomes
4-month Change in Maximal Treadmill Walking Time
Time frame: Baseline to 4 months
4-month Change in Calf Muscle Perfusion
Time frame: Baseline to 4 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36588397Nayak 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mary McDermott, MD principal investigator
Northwestern University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ghrelin in people with Peripheral Artery Disease, run by Northwestern University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Jun 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
4-month Change in Six-minute Walk Distance (time frame: Baseline to 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04377126, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2026.