Ghrelin in Healthy and Frail Older Women

Frailty Clinical Trial

Official title:

A Pilot Study of Ghrelin in Healthy and Frail Older Women

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00520884
• Other study ID #: IRB805400
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 2007
• Est. completion date: December 2008

Study information

• Verified date: May 2019
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: December 2008
• Est. primary completion date: December 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 70 Years and older

Eligibility

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:

1) average consumption of 3 or more alcohol containing beverages daily; 2) consumption of 7 or more alcoholic beverages within a 24 hr period in the past 12 months; or 3) clinical assessment of alcohol dependence based on two or more positive responses to an alcoholism questionnaire (if confirmed by further probing) or on other evidence available to clinic staff. If any of these exclusion criteria are met, the subject may still be considered eligible if, after an explanation of the importance of limiting alcohol intake during the study, the clinic staff believes that the volunteer can and will limit future alcohol intake to acceptable levels.

• History of gastrectomy

• Current therapy with an appetite stimulant, i.e. medroxyprogesterone acetate, within the last 6 weeks.

• Weight >85 kg

Related Conditions & MeSH terms

• Frailty

Intervention

Drug:
• 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.
• 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.

Other:
• 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.
• 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.

Locations

Country	Name	City	State
United States	University of Pennsylvania Clinical and Translational Research Center	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
University of Pennsylvania

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Kilocalories Consumed	Kilocalorie consumption from meal of standardized composition during the visit when infusion complete	After infusion
Primary	Max Change Growth Hormone	Maximum growth hormone level change from baseline to 180 minutes	180 minutes
Primary	Max Change Total Ghrelin	Maximum total ghrelin change from baseline to 180 minutes	180 minutes
Primary	Max Change Active Ghrelin	Active ghrelin change from baseline to 180 minutes. Active ghrelin=acylated ghrelin.	180 minutes