Ghrelin Repeated Dose Study

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.

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)