Clinical trial NCT01605435: Ghrelin Dose Finding In Frail Elderly
Official title: Ghrelin In Frail Elderly Subcutaneous Dose Finding Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: The Frailty Syndrome
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
First posted: 2012-05-24
Enrollment: 5
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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 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.

Detailed description: This study is to determine the optimal ghrelin dose for use in a daily subcutaneous dosing study in frail individuals. Using data from our previous study and the published literature, we have designed a single blind, single dose administration study in which we will examine food intake after ghrelin administration and metabolic parameters (plasma glucose, insulin, free fatty acids, and cortisol) pre and post ghrelin administration.We have selected a dose range using our own and previously published studies from which we will determine subcutaneous doses to use in subsequent studies. The selection criteria for subsequent studies will be the dose that maximizes food intake by more than 30% without inducing hyperglycemia or raising cortisol levels. Participants must meet all inclusion criteria and have no exclusion criteria. Data will be analyzed after the first three participants have completed the protocol and used to inform dose modifications for the next three participants. Data from this portion of the study will be analyzed immediately after its completion, to allow updates to the design of the next study.

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)

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Primary outcomes:
measure: Treatment Emergent Adverse Events
timeFrame: 30 days following the last administration of study treatment.
measure: Median Energy Intake
timeFrame: 30 mins post-ghrelin or placebo
measure: Percentage of Total Energy Intake Relative to Placebo
timeFrame: 30 mins post-ghrelin or placebo
measure: Growth Hormone
timeFrame: 30 minutes after ghrelin administration
measure: Cortisol Level
timeFrame: 0, 60 and 120 minutes after dosing
measure: Glucose Levels
timeFrame: 0 minutes (baseline) and 60 or 90 minutes from dosing
measure: Insulin Level
timeFrame: 0 and 90 minutes after dosing
measure: Free Fatty Acid Level
timeFrame: 90 and 120 minutes after dosing
Secondary outcomes:
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Clinical and Translational Research Center, University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: University Of Pennsylvania, Perelman School of Medicine, Department of Endocrinology, Diabetes and Metabolism
name: Anne R. Cappola, M.D., Sc.M.
role: PRINCIPAL_INVESTIGATOR
References: