Frailty Syndrome
Conditions
Keywords
Frailty, Sarcopenia, Weight Loss, Exercise, Aging, Ghrelin, Elderly
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.
Interventions
DRUGGhrelin
Ghrelin
DRUGPlacebo
Saline will be used as a placebo
Sponsors
University of Pennsylvania
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
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 uIU/L or greater than 10uIU/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. Hip fracture of hip or knee replacement within the previous 6 months or unable to walk 14. Deemed unsafe to participate by one of the study exercise therapists 15. Undergoing physical therapy or an exercise program 16. Unstable medical or psychological conditions or unstable home or food environment 17. Cognitive deficit as defined by a Folstein Mini Mental State Exam score \< 24/30 18. Depression (defined as a score of \> 11 on the Geriatric Depression Questionnaire) 19. Out of town for \> 1 week during the 12 week study 20. Residing outside of a 15 mile radius of University of Pennsylvania Health System
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 Weight | Baseline to twelve weeks | Change in weight from baseline to 12 weeks |
| 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 |
| 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 Lean Body Mass | Baseline to 12 weeks | Total lean body mass by dual energy x-ray absorptiometry |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ghrelin Plus Resistance Training Ghrelin 7.5 mcg/kg as a once daily subcutaneous dose for 12 weeks plus resistance training
Ghrelin: 2:1 ratio placebo to ghrelin
Resistance training: The exercise intervention will focus on twice weekly progressive strength training, taught by a certified fitness professional, to be performed in the home using dumbbells, an exercise step, and ankle weights. | 5 |
| Placebo Plus Resistance Training Placebo as a once daily subcutaneous dose for 12 weeks plus resistance training
Resistance training: The exercise intervention will focus on twice weekly progressive strength training, taught by a certified fitness professional, to be performed in the home using dumbbells, an exercise step, and ankle weights. | 10 |
| Total | 15 |
Baseline characteristics
| Characteristic | Placebo Plus Resistance Training | Ghrelin Plus Resistance Training | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 10 Participants | 5 Participants | 15 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 81.6 years STANDARD_DEVIATION 5 | 81.2 years STANDARD_DEVIATION 4 | 81.5 years STANDARD_DEVIATION 5 |
| Region of Enrollment United States | 10 participants | 5 participants | 15 participants |
| Sex: Female, Male Female | 6 Participants | 4 Participants | 10 Participants |
| Sex: Female, Male Male | 4 Participants | 1 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 11 |
| other Total, other adverse events | 0 / 5 | 0 / 11 |
| serious Total, serious adverse events | 0 / 5 | 1 / 11 |
Outcome results
Primary
Change in the Short Physical Performance Battery (SPPB)
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.
Time frame: Baseline to 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ghrelin Plus Resistance Training | Change in the Short Physical Performance Battery (SPPB) | 0.6 units on a scale | Standard Deviation 2.1 |
| Placebo Plus Resistance Training | Change in the Short Physical Performance Battery (SPPB) | 2.4 units on a scale | Standard Deviation 1.7 |
Primary
Treatment-associated Adverse Events
Treatment-associated emergent adverse events, including clinically meaningful changes in laboratory measurements (IGF-1, HbA1c, fasting blood glucose, fasting insulin).
Time frame: Twelve weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ghrelin Plus Resistance Training | Treatment-associated Adverse Events | 0 events |
| Placebo Plus Resistance Training | Treatment-associated Adverse Events | 0 events |
Secondary
Change in Food Intake
Change in food intake by 3-day food intake record
Time frame: Baseline to 12 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ghrelin Plus Resistance Training | Change in Food Intake | 298 kcal/day | Standard Deviation 127 |
| Placebo Plus Resistance Training | Change in Food Intake | -81 kcal/day | Standard Deviation 128 |
Secondary
Change in Frailty Status
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
Time frame: Baseline to 12 weeks.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Ghrelin Plus Resistance Training | Change in Frailty Status | 3.2 units on a scale |
| Placebo Plus Resistance Training | Change in Frailty Status | 3.4 units on a scale |
Secondary
Change in Lean Body Mass
Total lean body mass by dual energy x-ray absorptiometry
Time frame: Baseline to 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ghrelin Plus Resistance Training | Change in Lean Body Mass | 0.7 kg | Standard Deviation 0.8 |
| Placebo Plus Resistance Training | Change in Lean Body Mass | 1.0 kg | Standard Deviation 1.1 |
Secondary
Change in Muscle Strength
One repetition max bench press
Time frame: Baseline to 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ghrelin Plus Resistance Training | Change in Muscle Strength | 16 kg | Standard Deviation 21 |
| Placebo Plus Resistance Training | Change in Muscle Strength | 29 kg | Standard Deviation 25 |
Secondary
Change in Quality of Life
Quality of life as assessed by short form 36 (SF-36), higher score indicates better quality of life, scale is 0-100 points
Time frame: Baseline to 12 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ghrelin Plus Resistance Training | Change in Quality of Life | 8 score on a scale | Standard Deviation 13 |
| Placebo Plus Resistance Training | Change in Quality of Life | 4 score on a scale | Standard Deviation 8 |
Secondary
Change in Weight
Change in weight from baseline to 12 weeks
Time frame: Baseline to twelve weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ghrelin Plus Resistance Training | Change in Weight | -0.5 kg | Standard Deviation 0.5 |
| Placebo Plus Resistance Training | Change in Weight | 0.88 kg | Standard Deviation 1.8 |