Protocol Number: 03-DK-0257

Title:

Effect of Leptin Therapy in the Treatment of Severe Insulin Resistance

Number:

03-DK-0257

Summary:

Leptin is a hormone produced by the fat cells that researchers have shown to play a role in controlling appetite. Certain people with severe insulin resistance have little or no leptin.

The purpose of this study is to investigate people whose leptin levels have been found to be lower than 85 percent of the general population. Researchers will determine whether insulin levels in these participants improve when they are treated with genetically engineered leptin.

Study participants must be age 8 years or older and must have severe insulin resistance syndrome and leptin deficiency. During an initial 7-day visit to the Clinical Center, researchers will evaluate participants' metabolic parameters, such as insulin responsiveness, lipid levels, appetite, and hormone levels. After taking these tests, participants will self-inject doses of leptin once or twice a day and will be monitored for treatment outcomes as well as side effects via follow-up visits. These inpatient follow-up visits will involve both blood tests and imaging studies at the Clinical Center at 4, 8, and 12 months after the initial visit, and every 6 months thereafter.

Sponsoring Institute:

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

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: Yes

Population Exclusion(s): None

Eligibility Criteria:

INCLUSION CRITERIA:

Ethnicity: All ethnic groups.

Gender: Males and females.

Ages greater than 8 years.

Clinically significant, severe insulin resistance. This can be documented by a known or suspected defect in the insulin receptor, that have characteristic phenotypic identification. These include the following: Rabson Mendenhall syndrome, which usually is associated with mutations in the insulin receptor; Type A insulin resistance, which is usually associated with mutations in the insulin receptor; and Type B insulin resistance, which is associated with auto-antibodies to the insulin receptor. The inclusion criteria should include any patient with extreme insulin resistance who has appropriately low leptin levels. Syndromes of lipodystrophy are similar, but we already have approval to treat this group of patients.

Circulating leptin levels less than 6.0 ng/ml in females and less than 4.0 ng/ml in males as measured by Linco assay obtained from pooled samples collected fasting at 6 AM, 6:30 AM and 7 AM.

Presence of at least one of the following metabolic abnormalities:

a) Fasting insulin greater than 30 micro U/ml, or

b) Presence of diabetes as defined by the 1997 ADA criteria:

-Fasting plasma glucose greater than or equal to 126 mg/dL

-2 hour plasma glucose greater than or equal to 200 mg/dL following a 75 gram (1.75mg/kg if less than 40 kg) oral glucose load, or

-Diabetic symptoms with a random plasma glucose greater than or equal to 200 mg/dL.

EXCLUSION CRITERIA:

General: Pregnant women, women in their reproductive years who do not use an effective method of birth control, women currently nursing or lactating within 6 weeks of having completed nursing, and persons who are unable to provide informed consent will be excluded from the study.

Exclusions for underlying disease likely to increase side effects or to hinder objective data collection:

-Known infectious liver disease

-Current alcohol or substance abuse

-Psychiatric disorder impeding competence or compliance

-Active tuberculosis

-Use of anorexiogenic drugs

-Other conditions which in the opinion of the clinical investigators would impede completion of the study

-Subjects who have a known hypersensitivity to E. Coli derived proteins

Special Instructions: Currently Not Provided

Keywords:

Rabson Mendenhall

Type B Insulin Resistance

Type A Insulin Resistance

Diabetes

Recruitment Keywords:

None

Conditions:

Insulin Resistance

Investigational Drug(s):

hu Leptin (A-100)

Investigational Device(s):

None

Contacts:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:

Ahima RS, et al., Leptin accelerates the onset of puberty in normal female mice. J Clin Invest. 1997 Feb 1;99(3):391-5. PMID: 9022071

Ahima RS, et al., Distinct physiologic and neuronal responses to decreased leptin and mild hyperleptinemia. Endocrinology. 1999 Nov;140(11):4923-31. PMID: 10537115

Oral EA, et al., Leptin-replacement therapy for lipodystrophy. N Engl J Med. 2002 Feb 21;346(8):570-8. PMID: 11856796

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
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Bethesda, Maryland 20892. Last update: 10/15/2004