Frailty in Aging
Conditions
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 this study, the investigators are trying to find out if repeated daily doses of ghrelin will help frail older people improve food intake for multiple days in a row.
Detailed description
The study design is an open label, repeated dose administration study in which we will examine the safety and efficacy of repeated subcutaneous ghrelin administration in frail individuals. There will be a screening visit plus three additional study visits at the CTRC on Days 1, 2, and 7. Participants will receive an injection of ghrelin subcutaneously once daily on Days 1 and 7 and will self-administer the subcutaneous injection before breakfast on Days 2-6 at home. A food record will be kept from Day -3 to Day 6. We will assess the efficacy of repeated ghrelin doses to sustainably increase caloric intake from pre-treatment baseline without hyperglycemia or raising of cortisol levels.
Interventions
DRUGghrelin
ghrelin administration subcutaneously for 7 days
Sponsors
University of Pennsylvania
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
70 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Individuals with three, four or five frailty criteria using the Fried frailty criteria
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. New York Heart Association 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. Thyroid stimulating hormone 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 \< 24/30 15. Depression (defined as a score of \> 11 on the Geriatric Depression Questionnaire)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety | pre-treatment baseline through 30 days following the last administration of study treatment day 7 | 1.Safety: # of participants with treatment emergent adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sustainability of Increased Caloric Intake | pre-treatment baseline (day 1) through day 7 | Sustained food intake of standardized meal from Days 1 compared to Day 7. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from the outpatient medical practice serving the geriatric population at University of Pennsylvania via an electronic alert to physicians. Ten subjects were screened in order to obtain five eligible participants.
Participants by arm
| Arm | Count |
|---|---|
| Ghrelin ghrelin: ghrelin administration subcutaneously for 7 days | 5 |
| Total | 5 |
Baseline characteristics
| Characteristic | Ghrelin |
|---|---|
| Age, Continuous | 86 years |
| Region of Enrollment United States | 5 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 4 / 5 |
| serious Total, serious adverse events | 0 / 5 |
Outcome results
Primary
Safety
1.Safety: # of participants with treatment emergent adverse events
Time frame: pre-treatment baseline through 30 days following the last administration of study treatment day 7
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ghrelin | Safety | 4 participants |
Secondary
Sustainability of Increased Caloric Intake
Sustained food intake of standardized meal from Days 1 compared to Day 7.
Time frame: pre-treatment baseline (day 1) through day 7
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Ghrelin | Sustainability of Increased Caloric Intake | Baseline (day 1) | 691 calories |
| Ghrelin | Sustainability of Increased Caloric Intake | Day 7 | 839 calories |