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Protocol Details

Long-Term Efficacy of Leptin Replacement in Treatment of Lipodystrophy

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

02-DK-0022

Sponsoring Institute

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

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 6 mo
Max Age: N/A

Referral Letter Required

No

Population Exclusion(s)

None

Special Instructions

Currently Not Provided

Keywords

Lipoatrophic Diabetes;
Leptin;
Diabetes Mellitus;
Hypertriglyceridemia;
NASH

Recruitment Keyword(s)

Lipodystrophy;
Leptin;
Lipoatrophic Diabetes;
Diabetes

Condition(s)

Lipodystrophy

Investigational Drug(s)

Metreleptin

Investigational Device(s)

None

Intervention(s)

Drug: Metreleptin

Supporting Site

National Institute of Diabetes and Digestive and Kidney Diseases

This study will evaluate the safety and effectiveness of leptin replacement therapy in patients with lipodystrophy (also called lipoatrophy). Patients have a total or partial loss of fat cells. They also lack the hormone leptin, which is produced by fat cells. The leptin deficiency usually causes high blood lipid (fat) levels and insulin resistance that may lead to diabetes. Patients may have hormone imbalances, fertility problems, large appetite, and liver disease due to fat accumulation.

Patients age greater than or equal to 6 months with significant lipodystrophy may be eligible for this study. Candidates will be screened with a physical examination and blood tests. Participants will be admitted to the NIH Clinical Center for 10 days for the following studies before beginning 12 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 women 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.

Additional studies may include blood tests for genetic studies of lipodystrophy, a muscle biopsy to study muscle proteins involved in regulating energy expenditure before and after leptin replacement, and examination of a surgical specimen (if available) to study molecules that may be involved in energy storage and use.

When the above tests are completed, leptin therapy begins. The drug is injected under the skin twice a day for 4 months and then once a day, if feasible. The dose is increased at the 1- and 2-month visits. Follow-up visits at 1, 2, 4, 6, 8 and 12 months after therapy starts include a physical examination, blood tests and a meeting with a dietitian. At the end of 12 months, all baseline studies described above are repeated. Patients record their symptoms weekly throughout the study. Those with diabetes measure their blood glucose levels daily before each meal and at bedtime.

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Eligibility

INCLUSION CRITERIA:

All ethnic groups.

Males and females.

-Age greater than or equal to 6 months.

-Clinically significant lipodystrophy, identified by the study physician during the physical examination as an absence of fat outside the range of normal variation and/or identified as a disfiguring factor by the patient.

Circulating leptin levels less than 12.0 ng/ml in females and less than 8.0 ng/ml in males as measured by Linco assay on a specimen obtained after an overnight fast. In children ages 6 months 5 years, a circulating leptin level of less than 6 ng/mL will be used. Leptin samples will be run through Millipore Laboratories, who use the Linco Assay, which has been the assay previously used to measure leptin levels throughout this study period.

Presence of at least one of the following metabolic abnormalities:

1. Presence of diabetes as defined by the 2007 ADA criteria

a. Fasting plasma glucose greater than or equal to 126 mg/dL, or

b. 2 hour plasma glucose greater than or equal to 200 mg/dL following a 75 gram (1.75gm/kg) oral glucose load, or

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

2. Fasting insulin greater than 30 micro units/ml.

3. Fasting hypertriglyceridemia greater than 200 mg/dL or postprandially elevated triglycerides greater than 500 mg/dL when fasting is clinically not indicated (e.g. in infants)

-Persons with impaired decision-making capacity and who may be unable to provide informed consent may participate in this study per the discretion of the Principal Investigator.

EXCLUSION CRITERIA:

Pregnant women, women in their reproductive years who do not use an effective method of birth control, and women currently nursing or lactating within 6 weeks of having completed nursing.

Exclusions for underlying diseases likely to increase side effects or 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 condition(s) which in the opinion of the clinical investigators would impede completion of the study

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

-Subjects with acquired lipodystrophy and a hematologic abnormality such as neutropenia and/or lymphadenopathy


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Citations:

Troglitazone action is independent of adipose tissue

Life without white fat: a transgenic mouse

Nuclear lamin A/C R482Q mutation in canadian kindreds with Dunnigan-type familial partial lipodystrophy

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Contacts:

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
10 CENTER DR
BETHESDA MD 20814
(301) 402-7340
gordenp@extra.niddk.nih.gov

Elaine K. Cochran, C.R.N.P.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
BG 10-CRC RM 5-3961
10 CENTER DR
BETHESDA MD 20814
(301) 496-2718
elainer@intra.niddk.nih.gov

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

prpl@mail.cc.nih.gov

Clinical Trials Number:

NCT00025883

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