Ghrelin Plus Strength Training in Frail Elderly Study

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.

Study Overview

• Status: Completed
• Conditions: Frailty Syndrome
• Intervention / Treatment: Drug: Ghrelin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104-5160
      • Clinical and Translational Research Center, University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline to 12 weeks
Treatment-associated Adverse Events	Treatment-associated emergent adverse events, including clinically meaningful changes in laboratory measurements (IGF-1, HbA1c, fasting blood glucose, fasting insulin).	Twelve weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Weight	Change in weight from baseline to 12 weeks	Baseline to twelve weeks
Change in Lean Body Mass	Total lean body mass by dual energy x-ray absorptiometry	Baseline to 12 weeks
Change in Muscle Strength	One repetition max bench press	Baseline to 12 weeks
Change in Food Intake	Change in food intake by 3-day food intake record	Baseline to 12 weeks.
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	Baseline to 12 weeks.
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	Baseline to 12 weeks.

Collaborators and Investigators

• Sponsor: 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 record dates

Study Major Dates

• Study Start (Actual): July 1, 2013
• Primary Completion (Actual): August 31, 2016
• Study Completion (Actual): August 31, 2016

Study Registration Dates

• First Submitted: July 2, 2013
• First Submitted That Met QC Criteria: July 9, 2013
• First Posted (Estimate): July 12, 2013

Study Record Updates

• Last Update Posted (Actual): December 11, 2019
• Last Update Submitted That Met QC Criteria: November 26, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Elderly; Exercise; Aging; Weight Loss; Sarcopenia; Frailty; Ghrelin
• Additional Relevant MeSH Terms: Pathologic Processes; Frailty
• Other Study ID Numbers: 818192