Ghrelin Repeated Dose Study

Study Overview
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Brief Summary
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Frailty is a geriatric syndrome leading to physical deterioration including muscle wasting (sarcopenia) and unintentional weight loss. There are currently no approved therapies for frailty. Ghrelin is a hormone produced by the stomach that stimulates appetite centers in the brain. The investigators already know that a single dose of Ghrelin improves food intake immediately after the dose in frail older people. In this study, the investigators are trying to find out if repeated daily doses of ghrelin will help frail older people improve food intake for multiple days in a row.

Detailed Description
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The study design is an open label, repeated dose administration study in which we will examine the safety and efficacy of repeated subcutaneous ghrelin administration in frail individuals. There will be a screening visit plus three additional study visits at the CTRC on Days 1, 2, and 7. Participants will receive an injection of ghrelin subcutaneously once daily on Days 1 and 7 and will self-administer the subcutaneous injection before breakfast on Days 2-6 at home. A food record will be kept from Day -3 to Day 6. We will assess the efficacy of repeated ghrelin doses to sustainably increase caloric intake from pre-treatment baseline without hyperglycemia or raising of cortisol levels.

Official Title
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Ghrelin in Frail Elderly Subcutaneous Repeated Dose Study

Conditions
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Frailty in Aging

Intervention / Treatment
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* Drug: ghrelin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals with three, four or five frailty criteria using the Fried frailty criteria Exclusion Criteria: Diabetes mellitus or fasting glucose ≥ 126 mg/dL Hospitalization for stroke, myocardial infarction, coronary artery bypass graft surgery, vascular surgery in the past six months. New York Heart Association Class III or IV congestive heart failure Therapy for cancer in the past 12 months, except non-melanoma skin cancer BMI ≥ 30 kg/m2 Current use of corticosteroids other than topical, ophthalmic, and inhaled preparations Therapy with megestrol acetate or dronabinol within the last 6 weeks Thyroid stimulating hormone measured as < 0.4 mU/L or greater than 10mU/L Abnormal liver function tests (LFTs > 2x upper limit of normal) Hemoglobin < 11g/dL Insulin-like growth factor-I (IGF-I) above the age-specific reference range History of surgery within the last 30 days Unstable medical or psychological conditions or unstable home or food environment Cognitive deficit as defined by a Folstein Mini Mental State Exam score < 24/30 Depression (defined as a score of > 11 on the Geriatric Depression Questionnaire)

Ages Eligible for Study
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Minimum Age: 70 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 |
| --- | --- |
| Other: 7 day ghrelin dosing - all participants<br>All participants will receive an injection of ghrelin (7.5mcg/kg) dose subcutaneously once daily on Days 1, 2 and 7 in the research center and will self-administer the subcutaneous injection before breakfast on Days 2-6 at home. | Drug: ghrelin<br>* ghrelin administration subcutaneously for 7 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | 1.Safety: # of participants with treatment emergent adverse events | pre-treatment baseline through 30 days following the last administration of study treatment day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustainability of Increased Caloric Intake | Sustained food intake of standardized meal from Days 1 compared to Day 7. | pre-treatment baseline (day 1) through day 7 |