Ghrelin Dose Finding In Frail Elderly
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.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Subject)
|Official Title:||Ghrelin In Frail Elderly Subcutaneous Dose Finding Study|
- Safety [ Time Frame: 0, 15, 30, 45, 60, 90, 120 minutes ] [ Designated as safety issue: Yes ]laboratory measurements compared to placebo (pre- and post-prandial glucose, insulin, free fatty acids, and cortisol).
- Safety [ Time Frame: 0, 15, 30, 45, 60, 90, 120 minutes, 1 day later and through 30 days following the last administration of study treatment. ] [ Designated as safety issue: Yes ]Treatment emergent adverse events
- Efficacy [ Time Frame: 2 hours, 30 minutes post injection ] [ Designated as safety issue: No ]A standardized nutritionally balanced meal provided 30 minutes post injection ) and assessed for caloric intake two hours later based upon returned uneaten portion.
- Growth hormone, total ghrelin and active ghrelin profiles [ Time Frame: 0, 15, 30, 45, 60, 90 and 120 minutes ] [ Designated as safety issue: No ]
- Food Intake [ Time Frame: Day-1 and Day-2 ] [ Designated as safety issue: No ]Assessed via self reported food intake record on day 1 and day 2 post injection.
|Study Start Date:||May 2012|
|Study Completion Date:||December 2012|
|Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
Dose finding with each participant receiving placebo and three doses of ghrelin, separated by 3-7 days
The first three participants will receive 2 mcg/kg as a single subcutaneous dose at Visit 3, 5 mcg/kg as a single subcutaneous dose at Visit 4, and 10 mcg/Kg as a single subcutaneous dose at visit 5. There will be 3-10 days between visits. The next three participants will receive either the same dosing at the first three, a regimen that includes an intermediate dose (e.g., 7.5 mcg/kg), or higher (e.g., 12, 15, and 18 mcg/kg) doses.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01605435
|United States, Pennsylvania|
|Clinical and Translational Research Center, University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104|
|Principal Investigator:||Anne R. Cappola, M.D., Sc.M.||University Of Pennsylvania, Perelman School of Medicine, Department of Endocrinology, Diabetes and Metabolism|