Unacylated Ghrelin to Improve FuncTioning in PAD: The GIFT Trial

Study Overview
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Brief Summary
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The GIFT pilot study will investigate the optimal subcutaneous dose and safety of subcutaneously administered unacylated ghrelin in older people with peripheral artery disease (PAD).

Detailed Description
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The pilot GIFT Trial will obtain preliminary evidence to identify the optimal dose of subcutaneously administered unacylated ghrelin in people with PAD. The results of this pilot study may be used to design a randomized trial of unacylated ghrelin, in subsequent study, to improve functioning and prevent mobility loss in older people with PAD. In our primary specific aims, we will 1) establish the association of increasing doses of subcutaneous unacylated ghrelin with circulating levels of unacylated ghrelin 2) assess the safety of increasing doses of subcutaneously administered unacylated ghrelin in six patients with PAD age 55 and older. We will relate peak and Area Under the Curve values of unacylated ghrelin to brachial artery flow-mediated dilation (FMD) values. To achieve these aims, six PAD participants age 55 and older will receive a single subcutaneous injection of unacylated ghrelin at doses of 10 ug/kg, 20 ug/kg, and 40 ug/kg, respectively, on three separate days at least one week apart. Unacylated ghrelin levels will be measured at baseline and at defined intervals after each subcutaneous injection (30 minutes, 60 minutes, 1.5 hours, 3 hours, 6 hours, 8 to 12 hours and 24 hours). Brachial artery FMD will be measured at baseline, before the unacylated ghrelin injection, approximately six hours, and 24 hours after each unacylated ghrelin injection. Blood will be collected and stored for potential later analyses of circulating biomarkers, such as inflammatory biomarkers. This is a Phase I study to guide dose finding for a pilot study of unacylated ghrelin in people with PAD.

Official Title
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Unacylated Ghrelin to Improve FuncTioning in PAD: The GIFT Trial

Conditions
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PAD, Peripheral Artery Disease, Peripheral Arterial Disease

Intervention / Treatment
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* Drug: unacelyated ghrelin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. PAD patients age 55 and older Exclusion Criteria: Above or below-knee amputation, critical limb ischemia, and wheelchair confinement. Cardiovascular event during the previous three months. [Note: Participants who have undergone coronary revascularization for a cardiac event during the previous three months may still qualify.] Major medical illnesses including renal disease requiring dialysis, or cancer requiring treatment in the previous year. Participation in another clinical trial or completion of a clinical trial in the previous month, unless they were in the control group of the previous trial. Unwilling to attend nine study visits over approximately six months. Surgery including lower extremity revascularization or orthopedic surgery in the previous month or anticipated surgery in the next three months. Greater than 15 mmHg difference in blood pressure in both arm pressure measurements during the ankle brachial index (ABI), diagnosis of Raynaud's phenomenon, or unable to have the blood pressure checked in both arms. Blood pressure < 90/50 at baseline. Non-English speaking, a visual impairment that limits ability to read the consent, or a hearing impairment that interferes with study participation. 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.

Ages Eligible for Study
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Minimum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Subcutaneous injection of unacylated ghrelin: Doses of 10 ug/kg, 20 ug/kg, and 40 ug/kg | Drug: unacelyated ghrelin<br>* We will test doses of 10 ug/kg, 20 ug/kg, and 40 ug/kg of unacylated ghrelin on three separate days for each participant.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Levels of Unacylated Ghrelin | Levels of unacylated ghrelin are measured before and after every injection | Baseline and at scheduled intervals up to 24 hours after baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brachial Artery Flow-mediated Dilation (FMD) | Brachial artery flow-mediated dilation in response to hyperemia. The outcome is reporting the MAX Relative FMD 60/90 (%), which is calculated as the highest FMD between the RH60 and RH90 results, as a percent. | Baseline, 6-8 hours after baseline, 24 hours after baseline. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PAD, unacylated ghrelin, Peripheral Artery Disease