Ghrelin Plus Strength Training in Frail Elderly Study

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Completed
• CT.gov ID: NCT01898611
• Collaborator: (none)
• Enrollment: 16
• Location: 1
• Arms: 2
• Actual Duration (Months): 38
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Frailty Syndrome	Drug: Ghrelin; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Other
• Official Title: Ghrelin Plus Strength Training in Frail Elderly Study
• Actual Study Start Date: Jul 1, 2013
• Actual Primary Completion Date: Aug 31, 2016
• Actual Study Completion Date: Aug 31, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Ghrelin plus resistance training Ghrelin 7.5 mcg/kg as a once daily subcutaneous dose for 12 weeks plus resistance training	Drug: Ghrelin; Ghrelin
Placebo Comparator: Placebo plus resistance training Placebo as a once daily subcutaneous dose for 12 weeks plus resistance training	Drug: Placebo; Saline will be used as a placebo

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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 Outcome Measures

1. Change in Weight [Baseline to twelve weeks]

   Change in weight from baseline to 12 weeks

2. Change in Lean Body Mass [Baseline to 12 weeks]

   Total lean body mass by dual energy x-ray absorptiometry

3. Change in Muscle Strength [Baseline to 12 weeks]

   One repetition max bench press

4. Change in Food Intake [Baseline to 12 weeks.]

   Change in food intake by 3-day food intake record

5. 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

6. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 70 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical and Translational Research Center, University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104-5160

Sponsors and Collaborators

• University of Pennsylvania

Investigators

• Principal Investigator: Anne R. Cappola, M.D.,Sc.M., University of Pennsylvania, Perelman School of Medicine, Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Anne Cappola, Division of Endocrinology, Diabetes, and Metabolism, University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT01898611
• Other Study ID Numbers: 818192
• First Posted: Jul 12, 2013
• Last Update Posted: Dec 11, 2019
• Last Verified: Nov 1, 2019

• Keywords provided by Anne Cappola, Division of Endocrinology, Diabetes, and Metabolism, University of Pennsylvania: Frailty; Sarcopenia; Weight Loss; Exercise; Aging; Ghrelin; Elderly
• Additional relevant MeSH terms: Frailty

Study Results

Participant Flow

Arm/Group Title	Ghrelin Plus Resistance Training	Placebo Plus Resistance Training
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	5	11
COMPLETED	5	10
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Ghrelin Plus Resistance Training	Placebo Plus Resistance Training	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	5	10	15
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	5 100%	10 100%	15 100%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	81.2 (4)	81.6 (5)	81.5 (5)
Sex: Female, Male (Count of Participants)
Female	4 80%	6 60%	10 66.7%
Male	1 20%	4 40%	5 33.3%
Region of Enrollment (participants) [Number]
United States	5 100%	10 100%	15 100%

Outcome Measures

1. Primary Outcome

Title	Change in the Short Physical Performance Battery (SPPB)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ghrelin Plus Resistance Training	Placebo Plus Resistance Training
Arm/Group Description	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.	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.
Measure Participants	5	10
Mean (Standard Deviation) [units on a scale]	0.6 (2.1)	2.4 (1.7)

2. Primary Outcome

Title	Treatment-associated Adverse Events
Description	Treatment-associated emergent adverse events, including clinically meaningful changes in laboratory measurements (IGF-1, HbA1c, fasting blood glucose, fasting insulin).
Time Frame	Twelve weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ghrelin Plus Resistance Training	Placebo Plus Resistance Training
Arm/Group Description	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.	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.
Measure Participants	5	10
Number [events]	0	0

3. Secondary Outcome

Title	Change in Weight
Description	Change in weight from baseline to 12 weeks
Time Frame	Baseline to twelve weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ghrelin Plus Resistance Training	Placebo Plus Resistance Training
Arm/Group Description	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.	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.
Measure Participants	5	10
Mean (Standard Deviation) [kg]	-0.5 (0.5)	0.88 (1.8)

4. Secondary Outcome

Title	Change in Lean Body Mass
Description	Total lean body mass by dual energy x-ray absorptiometry
Time Frame	Baseline to 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ghrelin Plus Resistance Training	Placebo Plus Resistance Training
Arm/Group Description	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.	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.
Measure Participants	5	10
Mean (Standard Deviation) [kg]	0.7 (0.8)	1.0 (1.1)

5. Secondary Outcome

Title	Change in Muscle Strength
Description	One repetition max bench press
Time Frame	Baseline to 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ghrelin Plus Resistance Training	Placebo Plus Resistance Training
Arm/Group Description	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.	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.
Measure Participants	5	10
Mean (Standard Deviation) [kg]	16 (21)	29 (25)

6. Secondary Outcome

Title	Change in Food Intake
Description	Change in food intake by 3-day food intake record
Time Frame	Baseline to 12 weeks.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ghrelin Plus Resistance Training	Placebo Plus Resistance Training
Arm/Group Description	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.	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.
Measure Participants	5	10
Mean (Standard Deviation) [kcal/day]	298 (127)	-81 (128)

7. Secondary Outcome

Title	Change in Quality of Life
Description	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ghrelin Plus Resistance Training	Placebo Plus Resistance Training
Arm/Group Description	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.	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.
Measure Participants	5	10
Mean (Standard Deviation) [score on a scale]	8 (13)	4 (8)

8. Secondary Outcome

Title	Change in Frailty Status
Description	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ghrelin Plus Resistance Training	Placebo Plus Resistance Training
Arm/Group Description	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.	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.
Measure Participants	5	10
Mean (Full Range) [units on a scale]	3.2	3.4

Adverse Events

Arm/Group Title	Ghrelin Plus Resistance Training		Placebo Plus Resistance Training
Arm/Group Description	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.		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.
All Cause Mortality
	Ghrelin Plus Resistance Training		Placebo Plus Resistance Training
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/11 (0%)
Serious Adverse Events
	Ghrelin Plus Resistance Training		Placebo Plus Resistance Training
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		1/11 (9.1%)
Blood and lymphatic system disorders
Pulmonary embolism	0/5 (0%)	0	1/11 (9.1%)	1
Other (Not Including Serious) Adverse Events
	Ghrelin Plus Resistance Training		Placebo Plus Resistance Training
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/11 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.