Leptin to Treat Severe Insulin Resistance - Pilot Study
|First Received Date ICMJE||December 7, 2001|
|Last Updated Date||March 3, 2008|
|Start Date ICMJE||November 2001|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00027456 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Leptin to Treat Severe Insulin Resistance - Pilot Study|
|Official Title ICMJE||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:
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.
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 ICMJE||Interventional|
|Study Phase||Phase 2|
|Study Design ICMJE||Endpoint Classification: Safety/Efficacy Study
Primary Purpose: Treatment
|Intervention ICMJE||Drug: Leptin A-100|
|Study Arm (s)||Not Provided|
|Publications *||Scheen AJ, Paquot N, Letiexhe MR, Paolisso G, Castillo MJ, Lefebvre PJ. Glucose metabolism in obese subjects: lessons from OGTT, IVGTT and clamp studies. Int J Obes Relat Metab Disord. 1995 Sep;19 Suppl 3:S14-20. Review.|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Completion Date||December 2002|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
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.
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Location Countries ICMJE||United States|
|NCT Number ICMJE||NCT00027456|
|Other Study ID Numbers ICMJE||020060, 02-DK-0060|
|Has Data Monitoring Committee||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)|
|Collaborators ICMJE||Not Provided|
|Investigators ICMJE||Not Provided|
|Information Provided By||National Institutes of Health Clinical Center (CC)|
|Verification Date||December 2002|
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