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Protocol Details

Effect of Leptin Therapy in the Treatment of Severe Insulin Resistance

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

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

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 5
Max Age: N/A

Referral Letter Required


Population Exclusion(s)


Special Instructions

Currently Not Provided


Rabson Mendenhall;
Type B Insulin Resistance;
Type A Insulin Resistance;

Recruitment Keyword(s)



Insulin Resistance

Investigational Drug(s)


Investigational Device(s)



Drug: Metreleptin

Supporting Site

National Institute of Diabetes and Digestive and Kidney Diseases

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.

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Ethnicity: All ethnic groups.

Gender: Males and females.

Ages greater than 5 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 12.0 ng/ml in females and less than 6.0 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 2006 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.


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

-Known HIV infection

-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

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Park JY, Gavrilova O, Gorden P. The clinical utility of leptin therapy in metabolic dysfunction. Minerva Endocrinol. 2006 Jun;31(2):125-31.

Musso C, Cochran E, Moran SA, Skarulis MC, Oral EA, Taylor S, Gorden P. Clinical course of genetic diseases of the insulin receptor (type A and Rabson-Mendenhall syndromes): a 30-year prospective. Medicine (Baltimore). 2004 Jul;83(4):209-22.

Cochran E, Young JR, Sebring N, DePaoli A, Oral EA, Gorden P. Efficacy of recombinant methionyl human leptin therapy for the extreme insulin resistance of the Rabson-Mendenhall syndrome. J Clin Endocrinol Metab. 2004 Apr;89(4):1548-54.

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Principal Investigator

Referral Contact

For more information:

Phillip Gorden, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
BG 10-CRC RM 6-5952
(301) 402-7340

Elaine K. Cochran, C.R.N.P.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
BG 10-CRC RM 5-3961
(301) 496-2718

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

Protocol Consents:

Link to Protocol Consents

Public View: 03-DK-0257

Clinical Trials Number:


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