Clinical trial NCT00520884
Conditions: Frailty
Keywords: frailty ghrelin appetite weight loss
Sponsor: University of Pennsylvania
Start date: 2007-03-01; Completion date: 2008-12-01
Enrollment: 10 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
The purpose of this research study is to see if giving women a hormone called "ghrelin" will increase levels of growth hormone in the blood and increase appetite. Ghrelin is a naturally occurring hormone that is produced mostly by the stomach and causes secretion of another hormone called growth hormone. It also increases short-term appetite and may lower the amount of inflammation in the body.

Some people lose their appetite as they age and have unintentional weight loss. This may be caused by a break in the communication between the stomach and the brain. We are particularly interested in seeing if there is a difference in the effects of ghrelin in older women who have lost weight recently without wanting to and those who have not.

Detailed description:
Five community-dwelling women aged 70 or over with unintentional weight loss of \>5% in the prior year plus at least 2 of the 4 remaining Fried criteria for frailty and five healthy women without any frailty criteria were enrolled. Women with conditions that can cause weight loss or taking an appetite stimulant or corticosteroids were excluded. Each woman completed two 180 minute infusions, one week apart, assigned randomly: a graded ghrelin infusion of 2.5, 5.0, and 10.0 pmol/kg/min for 60 minutes each and an equivalent placebo (saline) infusion. A meal of standardized composition was provided after each infusion and intake quantified. Samples were collected every 30 minutes for growth hormone (GH), and total and active ghrelin. Additional samples were collected every 60 minutes for glucose, insulin, free fatty acids, leptin, adiponectin, resistin, glucagon-like peptide-1 receptor agonists (GLP-1), and cortisol. Adverse events were collected during the infusion and by telephone 24 hours later. Non-parametric methods were used to compare differences in response to the ghrelin and placebo infusions 1) in all women and 2) between frail and healthy women.

Arms: arm 1: Healthy and Frail Women 70 and Older Receive a 3 hour Placebo Infusion of Saline administered in a stepwise fashion in amounts equivalent to the ghrelin infusion. arm 2: Frail Women 70 and Older Receive a 3 hour Placebo Infusion of Saline administered in a stepwise fashion in amounts equivalent to the ghrelin infusion. arm 3: Healthy Women 70 and Older are administered a 3 hour graded Ghrelin Infusion (the first hour of the ghrelin infusion a dose of 2.5 pmol/kg/min, increased to a dose of 5.0 pmol/kg/min for one hour, and then increased to the dose of 10 pmol/kg/min for the final hour of the infusion). arm 4: Frail Women 70 and Older are administered a 3 hour graded Ghrelin Infusion (the first hour of the ghrelin infusion at a dose of 2.5 pmol/kg/min, increased to a dose of 5.0 pmol/kg/min for one hour, and then increased to the dose of 10 pmol/kg/min for the final hour of the infusion).
Interventions: intervention 1: Ghrelin Infusion - Healthy intervention 2: Ghrelin Infusion - Frail intervention 3: Placebo Infusion -Healthy intervention 4: Placebo Infusion - Frail
Intervention descriptions: intervention 1: At time 0, a graded infusion of Ghrelin of 2.5, 5.0, and 10.0 pmol/kg/min infused in one of the IV sites for 60 minutes each, totalling 180 minutes when the infusion will be stopped. intervention 2: At time 0, a graded infusion of Ghrelin of 2.5, 5.0, and 10.0 pmol/kg/min will be infused in one of the IV sites for 60 minutes each, totalling 180 minutes when the infusion will be stopped. intervention 3: At time 0, an infusion of saline will be started in one of the IV sites (an equivalent amount to compare to the Ghrelin infusion) and will be infused in a stepwise fashion continued until 180 minutes, when the infusion will be stopped. intervention 4: At time 0, an infusion of saline will be started in one of the IV sites (an equivalent amount to compare to the Ghrelin infusion) and will be infused in a stepwise fashion continued until 180 minutes, when the infusion will be stopped.

Protocol documents: