Ghrelin Dose Finding In Frail Elderly

• Status: Completed
• Trial end date: 2012-12-01
• Target enrollment: 0
• Participant gender: All

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 purpose of this study is to determine the optimal subcutaneous ghrelin dose as a potential intervention for frail elderly individuals. We will examine food intake and metabolic parameters after placebo and ghrelin administration at three escalating subcutaneously administered doses.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Pennsylvania

Criteria

Inclusion Criteria:

• We will include men and women aged 70 or older who are able to provide informed consent and are frail by the Fried criteria (Table 1).

• Table 1. Frailty criteria. Individuals with three, four, or all five criteria are frail.

• Weight loss: Unintentional weight loss of >5% over the previous year

Exhaustion: Two statements are read:

• I felt that everything I did was an effort

• I could not get going. The question is asked "How often in the last week did you feel this way?" 0 = rarely or none of the time (<1 day), 1 = some or a little of the time (1-2 days), 2 = a moderate amount of the time (3-4 days), or 3 = most of the time. A "2" or "3" response to either question is a positive response.

• Low physical activity: Kcal/week of physical activity calculated from the short version of the Minnesota Leisure Time Activity questionnaire.40 < 383 kcals in men or < 270 kcals/wk in women is positive for this criterion.

• Slow walking speed: A usual pace, 15-ft walk timed from a defined standing start. For men ≤173 cm tall and women ≤159 cm, ≥7 sec, and for men >173 cm and women > 159 cm, ≥ 6 sec is positive for this criterion.

• Weakness: Hand grip strength measured with a dynamometer. The average of three measurements performed in the dominant hand is used. For men with BMI ≤ 24 kg/m2, the cutoff is ≤ 29 kg, for BMI 24.1 to 26 the cutoff is ≤ 30 kg, for BMI 26.1 to 28 the cutoff is ≤30 kg, and for BMI > 28 the cutoff is ≤ 32 kg. For women with BMI ≤ 23 kg/m2, the cutoff is ≤ 17 kg, for BMI 23.1 to 26 the cutoff is ≤ 17.3 kg, for BMI 26.1 to 29 the cutoff is ≤ 18 kg, and for BMI > 29 the cutoff is ≤ 21 kg for a positive criterion.

Exclusion Criteria:

1. Diabetes mellitus or fasting glucose ≥ 126 mg/dL

2. Hospitalization for stroke, myocardial infarction, coronary artery bypass graft surgery, vascular surgery in the past six months.

3. NYHA Class III or IV congestive heart failure

4. Therapy for cancer in the past 12 months, except non-melanoma skin cancer

5. BMI≥ 30 kg/m2

6. Current use of corticosteroids other than topical, ophthalmic, and inhaled preparations

7. Therapy with megestrol acetate or dronabinol within the last 6 weeks

8. TSH measured as <0.4 mU/L or greater than 10mU/L

9. Abnormal liver function tests (LFTs > 2x upper limit of normal)

10. Hemoglobin < 11g/dL

11. Insulin-like growth factor-I (IGF-I) above the age-specific reference range

12. History of surgery within the last 30 days

13. Unstable medical or psychological conditions or unstable home or food environment

14. Cognitive deficit as defined by a Folstein Mini Mental State Exam score < 18/30

15. Depression (defined as a score of >11 on the Geriatric Depression Questionnaire)

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