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

A Pilot Study of the fMRI Response to Leptin and Pramlintide

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Obesity
• Intervention / Treatment: Drug: Placebo (Normal Saline); Drug: 2 Metreleptin; Drug: Pramlintide (Amylin); Drug: Leptin plus Pramlintide

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.

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Oregon Health and Science University
• Investigators: Principal Investigator: Jonathan Q. Purnell, M.D., OHSU - Center for the Study of Weight Regulation

Study record dates

Study Major Dates

• Study Start: January 1, 2006
• Primary Completion (Anticipated): July 1, 2024
• Study Completion (Anticipated): July 1, 2024

Study Registration Dates

• First Submitted: June 2, 2008
• First Submitted That Met QC Criteria: June 4, 2008
• First Posted (Estimate): June 5, 2008

Study Record Updates

• Last Update Posted (Actual): December 16, 2022
• Last Update Submitted That Met QC Criteria: December 14, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Appetite Depressants; Anti-Obesity Agents; Amylin Receptor Agonists; Pramlintide; Islet Amyloid Polypeptide
• Other Study ID Numbers: eIRB #2168; OCTRI #933 (Other Identifier: Oregon Health and Sciences University)