Leptin to Treat Severe Insulin Resistance - Pilot Study
Status:
Completed
Trial end date:
2002-12-01
Target enrollment:
Participant gender:
Summary
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.
Phase:
Phase 2
Details
Lead Sponsor:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)