Leptin to Treat Severe Insulin Resistance - Pilot Study

March 3, 2008 updated by: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Efficacy of Leptin in Severe Insulin Resistance: A Pilot Study

This pilot study will evaluate the safety and effectiveness of leptin therapy in two children with severe insulin resistance syndrome. Patients with this condition often have high blood sugar levels and may have hormone imbalances, a constant feeling of warmth, fertility problems, large appetite, and enlarged liver due to fat accumulation. Leptin is a hormone produced by fat cells. It influences appetite, affects levels of reproductive hormones, and possibly manages how the body reacts to insufficient food. Certain people with severe insulin resistance syndromes have decreased amounts of fat tissue and make little or no leptin.

A 13-year-old male and an 11-year-old female with severe insulin resistance will participate in this study. They will have the following tests and procedures before beginning 4 months of leptin therapy:

  • Insulin tolerance test - measures blood sugar levels after intravenous (IV) administration of insulin. Blood samples are collected through the IV tube at various intervals during the 1-hour test.
  • Ultrasound of the liver and, if abnormalities are found, possibly liver biopsies.
  • Fasting blood tests - to measure blood count, blood lipids, and various hormones and assess liver function.
  • Resting metabolic rate - to measure the amount of oxygen breathed at rest in order to calculate how many calories are required to maintain resting body functions.
  • Magnetic resonance imaging of the liver and other organs, and of muscle and fat.
  • Pelvic ultrasound in female patient - to detect ovarian cysts.
  • Estimation of body fat - measurements of height, weight, waist, hip size, and skin folds over the arms and abdomen to estimate body fat content.
  • Oral glucose tolerance test - measures blood sugar and insulin levels. The patient drinks a very sweet drink containing glucose (sugar), after which blood samples are collected through an IV tube in an arm vein at various intervals during the 3-hour test.
  • Intravenous glucose tolerance test - measures tissue response to insulin and glucose after glucose injection and insulin infusion. Blood is collected over 3 hours to measure insulin and glucose levels.
  • Appetite level and food intake - to measure hunger level and caloric intake. Patients are questioned about their hunger level, given a variety of foods they may choose to eat and questioned again at various intervals about hunger level. On another day, patients are given breakfast (usually a milkshake) and when they want to eat again, the appetite level and caloric intake study is repeated.
  • Hormone function tests - the function of three hormones influenced by leptin (corticotropin-releasing hormone, thyrotropin-releasing hormone and luteinizing hormone-releasing hormone) are assessed. The hormones are injected intravenously and then blood samples are drawn.
  • Questionnaire - patients complete a questionnaire about their activities and how they feel.
  • 24-hour urine collections - to measure specific hormones, proteins and sugars excreted in the urine.

When the above tests are completed, leptin therapy will start. The drug is injected under the skin twice a day for 4 months. Patients will record their symptoms weekly throughout the study. Those with diabetes will measure their blood glucose levels daily before each meal and at bedtime. Follow-up visits at 1, 2 and 4 months after therapy will include a physical examination, blood tests and a meeting with a dietitian. At the 4-month visit, the tests done at the beginning of the study will be repeated.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Over the course of the year, we have observed that recombinant leptin has the potential to act as an insulin-sensitizer in subjects with lipoatrophy and leptin deficiency. The exact mechanisms of this effect are not known. We would like to test whether leptin will work as an insulin-sensitizer in a situation where the mechanism of insulin resistance is known, namely in a situation where there is a known defect on the insulin receptor. This will allow us to learn if leptin can overcome a receptor defect by activating some of the down-stream molecules in insulin signaling cascade.

We would like to begin exploring this question in two patients with mutations on their insulin receptor, who are in need of improved treatment. In fact, in these two patients, the conventional therapeutic options have not provided adequate control of blood sugar levels. Furthermore, the circulating leptin concentrations in these two patients are lower than the 15th percentile of normal population. Therefore, a strategy to achieve physiological concentrations of leptin hormone using recombinant leptin (A100, recombinant methionyl-human leptin) will be justified.

We also plan to keep the initial observation period short. Since we have observed insulin-sensitizing effects of leptin in lipoatrophy within 4 months, we will limit the initial treatment period to 4 months. The regime will be similar to the regimen used in lipoatrophic patients. The starting dose will be 50% of replacement dose and this will be incrementally increased to 200% replacement dose within the course of two months. The medication will be administered subcutaneously in two divided doses. Plasma glucose concentrations and HbA1c are designated as primary outcome measures. Data on the effects of leptin hormone on appetite, insulin secretion and sensitivity and other pituitary hormones will also be collected as pilot data. At the end of 4 months, we will make a decision to continue therapy and to broaden the study by opening recruitment to other similar patients.

Study Type

Interventional

Enrollment

2

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • ADULT
  • OLDER_ADULT
  • CHILD

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

INCLUSION CRITERIA:

This pilot study will be limited to two minor subjects with the exceptionally rare Rabson-Mendenhall syndrome that were already enrolled in studies of extreme insulin resistance at the NIH.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2001

Study Completion

December 1, 2002

Study Registration Dates

First Submitted

December 7, 2001

First Submitted That Met QC Criteria

December 6, 2001

First Posted (ESTIMATE)

December 7, 2001

Study Record Updates

Last Update Posted (ESTIMATE)

March 4, 2008

Last Update Submitted That Met QC Criteria

March 3, 2008

Last Verified

December 1, 2002

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 020060
  • 02-DK-0060

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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