Kisspeptin Influence on Glucose Homeostasis

Study Overview
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Brief Summary
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The goal of this study is to learn about how a naturally occurring hormone called kisspeptin affects blood sugar and insulin levels.

Official Title
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Kisspeptin Influence on Glucose Homeostasis

Conditions
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Hypogonadism, Impaired Glucose Tolerance

Intervention / Treatment
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* Drug: kisspeptin 112-121
* Other: Insulin Resistance Test
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion/Exclusion Criteria: History: normal pubertal development stable weight for previous three months no active illicit drug use, no history of a medication reaction requiring emergency medical care, no difficulty with blood draws. Physical examination: • systolic BP < 140 mm Hg, diastolic < 90 mm Hg, Laboratory studies: (per MGH reference ranges) normal hemoglobin, unless hypogonadal then no lower than 0.5 gm/dL below the lower limit of the reference range for normal women (as men and women with hypogonadism have lower hemoglobin levels off of treatment) hemoglobin A1C < 6.5% BUN, creatinine not elevated AST, ALT < 3x upper limit of normal negative serum pregnancy test (for all women) no hyperlipidemia by fasting lipid panel Additional Criteria by Study Population Healthy Men: normal body mass index (BMI between 18.5-25) no history of chronic disease, except well controlled thyroid disease no recent use of prescription medications which interfere with metabolism or reproduction. Use of levothyroxine or seasonal allergy medications is acceptable. no history of diabetes in a first degree relative. Healthy Women: normal body mass index (BMI between 18.5-25) no history of chronic disease, except well controlled thyroid disease, no recent use of prescription medications which interfere with metabolism or reproduction. Use of levothyroxine or seasonal allergy medications is acceptable. no history of diabetes in a first degree relative, no use of contraceptive pills, patches or vaginal rings within last 4 weeks. regular menstrual cycles Postmenopausal Women: body mass index (BMI between 18.5-30) no history of chronic disease except thyroid disease, and osteoporosis, no recent use of prescription medications which interfere with metabolism or reproduction. Use of levothyroxine, osteoporosis medications or seasonal allergy medications is acceptable, no history of diabetes in a first degree relative, normal activate protein C resistance screen, if applicable, able to undergo appropriate washout from hormone therapy. Men and Women with Impaired Glucose Tolerance (IGT): diagnosis of impaired glucose tolerance by oral glucose tolerance test, all medical conditions well-controlled. Men and Women with Hypogonadism diagnosis of hypogonadism, all other medical conditions well-controlled, if applicable, able to undergo appropriate washout from hormone therapy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Kisspeptin and Insulin Resistance Test<br>Intravenous (IV) administration of kisspeptin 112-121; eat a standard mixed meal or drink a standard mixed meal or 75 grams of oral glucose | Drug: kisspeptin 112-121<br>* Dose: 0.313-12.5 mcg/kg Duration: up to 16 hours<br>* Other names: metastin 45-54;Other: Insulin Resistance Test<br>* Eat or drink a standard meal OR drink a standard drink containing 75 grams of sugar<br>|
| Placebo Comparator: Placebo and Insulin Resistance Test<br>IV administration of fluids that contain no study drug; eat a standard mixed meal or drink a standard mixed meal or 75 grams of oral glucose | Other: Insulin Resistance Test<br>* Eat or drink a standard meal OR drink a standard drink containing 75 grams of sugar<br>Other: Placebo<br>* Receive IV fluids for up to 16 hours that do not contain any study drug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average difference in area under the curve of insulin in response to a mixed meal tolerance test | Compares difference on and off kisspeptin | 4 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average difference in area under the curve of glucose in response to a mixed meal tolerance test | Compares difference on and off kisspeptin | 4 hours | 
| Average difference in area under the curve of glucagon-like peptide 1 in response to a mixed meal tolerance test | Compares difference on and off kisspeptin | 4 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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insulin regulation in pregnancy, kisspeptin