Ghrelin in Healthy and Frail Older Women

NCT ID: NCT00520884

Last Updated: 2019-06-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-03-31
• Study Completion Date: 2008-12-31

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.

Conditions

Frailty

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: TRIPLE

Study Groups

Healthy 70+ Women Placebo Infusion

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.

Group Type: PLACEBO_COMPARATOR

Placebo Infusion -Healthy

Intervention Type: OTHER

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.

Frail 70+ Women Placebo Infusion

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.

Group Type: PLACEBO_COMPARATOR

Placebo Infusion - Frail

Intervention Type: OTHER

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.

Healthy 70+ Women Ghrelin Infusion

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).

Group Type: ACTIVE_COMPARATOR

Ghrelin Infusion - Healthy

Intervention Type: DRUG

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.

Frail 70+ Women Ghrelin Infusion

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).

Group Type: ACTIVE_COMPARATOR

Ghrelin Infusion - Frail

Intervention Type: DRUG

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.

Interventions

Ghrelin Infusion - Healthy

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 Type: DRUG

Ghrelin Infusion - Frail

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 Type: DRUG

Placebo Infusion -Healthy

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 Type: OTHER

Placebo Infusion - Frail

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 Type: OTHER

Other Intervention Names

Healthy Older Women Receiving; Frail Older Women Receiving; Healthy Older Women Receiving; Frail Older Women Receiving

Eligibility Criteria

Inclusion Criteria

Frail group:

• Women aged 70 or greater
• Able to give informed consent
• Undiagnosed weight loss (>5% over the previous year)
• Two of the following four criteria (from Fried L et al, 2001): low grip strength, slow walking speed, subjective exhaustion, low levels of physical activity

Healthy group:

• Women aged 70 or greater
• Able to give informed consent
• None of the frailty criteria

Exclusion Criteria

• Prior diagnosis of Parkinson's Disease
• History of cerebrovascular accident with residual hemiparesis
• Hospitalization for treatment of vascular disease (including, coronary heart disease, cerebrovascular disease, peripheral vascular disease) in the past 6 months
• Congestive heart failure
• Rheumatoid arthritis or other inflammatory conditions
• Depression (defined as a score of >11 on the Geriatric Depression Questionnaire)
• History of cancer requiring treatment in the past 5 years, with the exception of cancers which have been cured, or, in the opinion of the investigator, carry a good prognosis
• Cognitive deficit as defined by a Folstein Mini Mental State Exam score < 18/30
• Current use of corticosteroids or immune-modulating agents other than topical, ophthalmic, and inhaled preparations, in past 3 months
• Diabetes mellitus
• Thyroid stimulating hormone (TSH) measured as <0.5 U/L or greater than 10 U/L. If participant is taking replacement thyroid hormone, they should be on a stable dose for at least 2 months
• History of liver disease or abnormal liver function tests (LFTs > 2x upper limit of normal)
• Renal insufficiency (serum creatinine ≥ 1.4 mg/dL).
• Hemoglobin < 11g/dL
• History of surgery within the last 30 days.
• Serious or unstable medical or psychological conditions that, in the opinion of the investigator, would compromise the subject's safety or successful participation in the study
• Participation in an investigational drug study within 6 weeks prior to screening visit
• Self reported history of HIV disease
• Hospitalization for chronic obstructive pulmonary disease or asthma in the past 3 months
• History of alcohol abuse as defined as any one of the following:

• History of gastrectomy
• Current therapy with an appetite stimulant, i.e. medroxyprogesterone acetate, within the last 6 weeks.
• Weight >85 kg

• Minimum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Anne Cappola

Associate Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Anne R Cappola, MD, ScM

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

University of Pennsylvania Clinical and Translational Research Center

Philadelphia, Pennsylvania, United States

Countries

United States

Other Identifiers

IRB805400

Identifier Type: -

Identifier Source: org_study_id