A Study of the Functional Magnetic Resonance Imaging Response to Leptin and Pramlintide

Study Overview
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Brief Summary
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The purpose of this study is to identify how certain parts of the brain that help control body weight respond to an infusion of hormones called leptin and amylin.

Detailed Description
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Following an overnight fast, subjects will undergo fMRI measurements of the hypothalamus, brainstem and whole brain during an infusion of either normal saline, pramlintide, leptin, or the combination leptin and pramlintide.

Official Title
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A Pilot Study of the fMRI Response to Leptin and Pramlintide

Conditions
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Obesity

Intervention / Treatment
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* Drug: Pramlintide (Amylin)
* Drug: Placebo (Normal Saline)
* Drug: 2 Metreleptin
* Drug: Leptin plus Pramlintide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 year to 45 years of age MI 18 to 25 kg/m2 or ≥ 30 kg/m2 At maximal lifetime weight Weight stable for at least 3 months Exclusion Criteria: Those with a major medical illness or who require prescription medication, including: cancer, coronary artery disease, hypertension, and diabetes. Subjects taking psychiatric or centrally-acting (CNS) medications or who are diagnosed with a psychiatric or neurological illness, including: depression anorexia bulimia seizure disorder. Exercise > 30 minutes, 3 times a week Alcohol consumption > 2 drinks / day Weight > 350 lbs (159 kg) (weight limit for MR machine) Illicit drug use Pregnancy Extreme dietary habits as determined by a GCRC nutritionist: very high or low dietary carbohydrate or fat intakes Those with a contraindication to exposure to strong magnetic fields: presence of metal in the body such as body piercing, shrapnel, cardiac pacemakers or aneurysm clips Those with claustrophobia Anaphylaxis and known hypersensitivity to E. coli-derived proteins Allergies or contraindications to metreleptin or pramlintide Renal or hepatic impairment Women who are lactating Tobacco use

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1- Normal Saline<br>4.7 mls normal saline IV bolus | Drug: Placebo (Normal Saline)<br>* 4.7 mls normal saline IV bolus x1<br>* Other names: Placebo;|
| Active Comparator: 2 Metreleptin<br>IV Leptin bolus | Drug: 2 Metreleptin<br>* Receive .06mg/kg of metreleptin IV bolus x1<br>* Other names: Leptin;|
| Active Comparator: 3 Pramlintide<br>IV Pramlintide bolus at Timpoint +0 and +30 minutes | Drug: Pramlintide (Amylin)<br>* 4.7 mls of Amylin 15mcg/ml IV bolus.<br>* Other names: Amylin;|
| Active Comparator: 4 Leptin plus Pramlintide<br>leptin and pramlintide IV bolus injection at timpoints 0 and +30 minutes | Drug: Leptin plus Pramlintide<br>* receive leptin IV bolus x1 and pramlintide bolus at Timepoint +0 and +30 minutes.<br>* Other names: Leptin and Amylin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To measure the fMRI response in the hypothalamus and brainstem, and whole brain, to intravenous leptin, pramlintide, combination leptin and pramlintide, and saline control. | measurements at each study time are include fMRI, blood draws and Visual Analog Score. | over 90 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Timed blood samples during infusion will establish the time course for peak levels of infused hormones as well as detectable changes in insulin and glucose levels. | Blood samples are taken every 5 minutes from Timepoint +0 to Timepoint +60 and again one time at Timepoint +90 | over 90 minutes |