Deacylated Ghrelin and Beta Cell Function

Study Overview
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Brief Summary
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Use of human unacylated ghrelin (UAG, also called des-octanoyl ghrelin) to study physiology in healthy subjects. The proposed research is an investigator-initiated study funded by the National Institutes of Health designed to examine the effect of physiologic levels of UAG on the regulation of glucose homeostasis as well as beta cell function.

Official Title
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Impact of Unacylated Ghrelin on Beta-cell Function in Humans

Conditions
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the Diabetic Process

Intervention / Treatment
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* Drug: unacylated ghrelin
* Drug: acyl ghrelin
* Drug: combined acyl and desacyl ghrelin
* Drug: saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Apparently healthy men and women. Only premenopausal women who are using an adequate method of contraception at Screening and who agree to continue the contraception during the study will be included. Male subjects do not need to use on birth control. Ages between 18 and 50 years, inclusive. BMI between 18.5 and 29.9 kg/m2, inclusive Exclusion Criteria: History or clinical evidence of impaired fasting glucose or impaired glucose tolerance or diabetes mellitus, myocardial infarction, history or symptoms of congestive heart failure, history of cancer or anorexia nervosa, history or active liver or renal disease (AST or ALT >2x upper limits of normal, calculated glomerular filtration rate [GFR] <60). A baseline resting systolic blood pressure of less than 100 mm Hg. History of growth hormone deficiency or excess disorders (acromegaly, pituitary gigantism, panhypopituitarism); history of adrenal insufficiency or Cushing's disease/syndrome; history of neuroendocrine tumors. Anemia defined as hematocrit <33%. Use of medications that alter insulin sensitivity: niacin, glucocorticoids, metformin, thiazolidinediones, exenatide, or atypical anti-psychotics. Pregnancy or lactation. BMI <18 kg/m2 or BMI >30 kg/m2; fasting plasma glucose >100 mg/dl and/or 2 hr plasma glucose >140 mg/dl on a 75 g oral glucose tolerance test. Electrocardiogram (ECG) abnormalities: specifically, myocardial ischemia, previous myocardial ischemia, atrial fibrillation, second or third degree heart block and complete right or left bundle branch block. Females who are on progesterone-only contraception and those who have irregular menses.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: decaylated ghrelin<br>UAG (4.0 µg/kg/hr) | Drug: unacylated ghrelin<br>* IV, UAG (4.0 µg/kg/hr), one time, duration of study visit (approximately 5 hours)<br>|
| Experimental: acyl ghrelin<br>AG (1.0 µg/kg/hr) | Drug: acyl ghrelin<br>* IV, AG (1.0 µg/kg/hr), one time, duration of study visit (approximately 5 hours)<br>|
| Experimental: combined acyl and desacyl ghrelin<br>the combination of AG (1 µg/kg/hr) and UAG (4 µg/kg/hr) | Drug: combined acyl and desacyl ghrelin<br>* IV, the combination of AG (1 µg/kg/hr) and UAG (4 µg/kg/hr), one time, for the duration of the study visit (approximately 5 hours)<br>|
| Placebo Comparator: saline<br>saline | Drug: saline<br>* IV, saline, one time, for the duration of the study visit(approximately 5 hours)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| acute insulin release (AIRg) | The primary outcome measure will be AIRg. This is calculated as the incremental insulin release,following IV glucose administration. (For the first ten minutes of the study visit.) | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin sensitivity | 1. Insulin sensitivity is quantified as the insulin sensitivity index (SI) using Bergman's minimal model of glucose kinetics from the glucose and insulin results obtained from a FSIGT. | one year | 
| Disposition index | 2. The disposition index (DI) is a measure of β-cell function. It accounts for the modulating effect of insulin sensitivity on β-cell responses. It is calculated as the product of the SI and AIRg | one year | 
| glucose tolerance | 3. Glucose tolerance is measured by glucose disappearance constant. This is calculated as the slope of the natural log of glucose during the study visit, during a set time frame. | one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unacylated ghrelin, beta cell function