Ghrelin Plus Strength Training in Frail Elderly Study

Phase 2

Completed

Brief Summary: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Ghrelin plus resistance training	Ghrelin	Ghrelin 7.5 mcg/kg as a once daily subcutaneous dose for 12 weeks plus resistance training
Placebo plus resistance training	Placebo	Placebo as a once daily subcutaneous dose for 12 weeks plus resistance training

Primary Outcome Measures

Name	Time	Method
Change in the Short Physical Performance Battery (SPPB)	Baseline to 12 weeks	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.
Treatment-associated Adverse Events	Twelve weeks	Treatment-associated emergent adverse events, including clinically meaningful changes in laboratory measurements (IGF-1, HbA1c, fasting blood glucose, fasting insulin).

Secondary Outcome Measures

Name	Time	Method
Change in Weight	Baseline to twelve weeks	Change in weight from baseline to 12 weeks
Change in Lean Body Mass	Baseline to 12 weeks	Total lean body mass by dual energy x-ray absorptiometry
Change in Muscle Strength	Baseline to 12 weeks	One repetition max bench press
Change in Food Intake	Baseline to 12 weeks.	Change in food intake by 3-day food intake record
Change in Quality of Life	Baseline to 12 weeks.	Quality of life as assessed by short form 36 (SF-36), higher score indicates better quality of life, scale is 0-100 points
Change in Frailty Status	Baseline to 12 weeks.	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