Ghrelin Plus Strength Training in Frail Elderly 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 addition, exercise programs have been shown to improve strength and function in older people. In this study, the investigators are trying to find out if a joint intervention of ghrelin and resistance training will improve walking, balance and leg strength in frail elderly people.

Official Title
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Ghrelin Plus Strength Training in Frail Elderly Study

Conditions
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Frailty Syndrome

Intervention / Treatment
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* Drug: Ghrelin
* Drug: Placebo


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 uIU/L or greater than 10uIU/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 Hip fracture of hip or knee replacement within the previous 6 months or unable to walk Deemed unsafe to participate by one of the study exercise therapists Undergoing physical therapy or an exercise program 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) Out of town for > 1 week during the 12 week study Residing outside of a 15 mile radius of University of Pennsylvania Health System

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ghrelin plus resistance training<br>Ghrelin 7.5 mcg/kg as a once daily subcutaneous dose for 12 weeks plus resistance training | Drug: Ghrelin<br>* Ghrelin<br>|
| Placebo Comparator: Placebo plus resistance training<br>Placebo as a once daily subcutaneous dose for 12 weeks plus resistance training | Drug: Placebo<br>* Saline will be used as a placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Short Physical Performance Battery (SPPB) | The SPPB includes three components: gait speed on a 15-foot walk, standing balance testing, and time to rise from a chair 5 times. Each test is rated on a five-level categorical score, with 0 representing inability to complete the test and 4 representing the highest level of performance, and summed to create a score ranging from 0 to 12. | Baseline to 12 weeks | 
| Treatment-associated Adverse Events | Treatment-associated emergent adverse events, including clinically meaningful changes in laboratory measurements (IGF-1, HbA1c, fasting blood glucose, fasting insulin). | Twelve weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Weight | Change in weight from baseline to 12 weeks | Baseline to twelve weeks | 
| Change in Lean Body Mass | Total lean body mass by dual energy x-ray absorptiometry | Baseline to 12 weeks | 
| Change in Muscle Strength | One repetition max bench press | Baseline to 12 weeks | 
| Change in Food Intake | Change in food intake by 3-day food intake record | Baseline to 12 weeks. | 
| Change in Quality of Life | Quality of life as assessed by short form 36 (SF-36), higher score indicates better quality of life, scale is 0-100 points | Baseline to 12 weeks. | 
| Change in Frailty Status | According to the Fried frailty criteria: Weight loss, exhaustion, low physical activity, slow walking speed, weakness, range 0 to 5, higher score indicates more frailty | Baseline to 12 weeks. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Frailty, Sarcopenia, Weight Loss, Exercise, Aging, Ghrelin, Elderly