Clinical trial NCT00520884: Ghrelin in Healthy and Frail Older Women
Official title: A Pilot Study of Ghrelin in Healthy and Frail Older Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Frailty
Keywords: frailty
ghrelin
appetite
weight loss
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
First posted: 2007-08-27
Enrollment: 10
Sex: FEMALE
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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.

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:

  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

Primary outcomes:
measure: Kilocalories Consumed
timeFrame: After infusion
measure: Max Change Growth Hormone
timeFrame: 180 minutes
measure: Max Change Total Ghrelin
timeFrame: 180 minutes
measure: Max Change Active Ghrelin
timeFrame: 180 minutes
Secondary outcomes:
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: University of Pennsylvania Clinical and Translational Research Center
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Anne R Cappola, MD, ScM
role: PRINCIPAL_INVESTIGATOR
References: