Ghrelin Dose Finding In Frail Elderly
Condition: The Frailty Syndrome
MeSH terms: Frailty
Intervention: Ghrelin Group 1; Ghrelin Group 2
Intervention description: The first two participants received placebo at baseline visit, 2 mcg/kg as a single subcutaneous dose at Visit 2, 5 mcg/kg as a single subcutaneous dose at Visit 3, and 10 mcg/Kg as a single subcutaneous dose at visit 4. There was 3-10 days between visits.; The next three participants received placebo at baseline visit, 5 mcg/kg as a single subcutaneous dose at Visit 2, 7.5 mcg/kg as a single subcutaneous dose at Visit 3, and 10 mcg/Kg as a single subcutaneous dose at visit 4.
Phase: Phase 2
Study type: Interventional
Primary purpose: Other
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Enrollment: 5.0
Sex: All
Minimum age: 70 Years
Healthy volunteers: No

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.
    

Eligibility 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)

             -