Obesity
Conditions
Brief summary
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
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.
Interventions
DRUGPramlintide (Amylin)
4.7 mls of Amylin 15mcg/ml IV bolus.
DRUGPlacebo (Normal Saline)
4.7 mls normal saline IV bolus x1
DRUG2 Metreleptin
Receive .06mg/kg of metreleptin IV bolus x1
DRUGLeptin plus Pramlintide
receive leptin IV bolus x1 and pramlintide bolus at Timepoint +0 and +30 minutes.
Sponsors
Oregon Health and Science University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To measure the fMRI response in the hypothalamus and brainstem, and whole brain, to intravenous leptin, pramlintide, combination leptin and pramlintide, and saline control. | over 90 minutes | measurements at each study time are include fMRI, blood draws and Visual Analog Score. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | over 90 minutes | Blood samples are taken every 5 minutes from Timepoint +0 to Timepoint +60 and again one time at Timepoint +90 |
Countries
United States
Outcome results
None listed