Short-term Effects of Leptin in People With Lipodystrophy
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01778556|
Recruitment Status : Recruiting
First Posted : January 29, 2013
Last Update Posted : May 30, 2018
- Lipodystrophy is a condition where people do not have enough fat in the body. People with lipodystrophy can have problems such as diabetes or an enlarged liver. Researchers are looking at how leptin, a hormone produced by fat cells, can help people with these problems. Leptin helps control appetite and how the body stores food. Taking leptin can help people with lipodystrophy eat less food, which may help treat diabetes and other problems. To better understand how leptin works, researchers want to do an inpatient study on leptin treatment in people with lipodystrophy.
- To study how leptin treatment affects lipodystrophy.
- Individuals between 14 and 70 years of age who have lipodystrophy.
- All participants will have a 19-day stay at the National Institutes of Health Clinical Center. One group of participants will have tests for 5 days before starting to take leptin. They will then take leptin for 2 weeks, and have more tests. The other group of participants will have tests for 5 days while taking leptin. They will then take stop taking leptin for 2 weeks, and have more tests, and then they will start taking leptin again.
- Participants will have regular blood and urine tests during the visit. Some of the blood tests will look at insulin levels. Some will look at how the body metabolizes sugar and fat. Other tests will check hormone levels, especially of reproductive hormones.
- During the visit, participants will spend 3 separate days in a metabolic chamber, a special room that measures how many calories the body uses. Urine samples will be collected during these stays.
- Participants will also have several body imaging studies, including magnetic resonance imaging and a body composition scan.
- Physical activity will be tested with an exercise bicycle and an electronic activity monitor.
- Participants will be asked questions about hunger and comfort levels throughout the stay.
|Condition or disease||Intervention/treatment||Phase|
|Lipodystrophy||Biological: Metreleptin||Phase 2|
Leptin is an adipocyte-derived hormone that can be thought of as a signal from adipose tissue to the rest of the body conveying information about long-term nutritional status. Patients with lipodystrophy have leptin deficiency secondary to lack of adipose tissue, and thus represent a natural model for studying the effects of leptin deficiency and replacement in humans. Leptin replacement in lipodystrophy ameliorates metabolic and endocrine abnormalities, including reducing food intake, improving insulin resistance and diabetes, reducing ectopic lipid, and normalizing reproduction. The reduction in energy intake induced by leptin replacement is likely responsible for part of the improvements observed in glucose and lipid metabolism. The clinical effects of leptin that are independent of changes in energy intake, and the mechanisms underlying these effects, have been poorly explored in humans.
The primary aim of this study is to determine the energy intake-independent effects of leptin on energy metabolism in lipodystrophic subjects. The major aspects of energy metabolism to be studied are:
- Lipid metabolism, including fasting lipids, lipolysis and fatty acid turnover, and ectopic lipid storage.
- Glucose metabolism, including fasting glucose, endogenous glucose production, and insulin sensitivity
- Energy expenditure, including total and resting energy expenditure, skeletal muscle work efficiency, and spontaneous physical activity
In addition, the effects of leptin on endocrine and autonomic function will be examined, including effects on the thyroid, gonadal, and adrenal axes, as well as blood pressure, body temperature, and heart rate variability.
This is a non-randomized, parallel group study. Two groups of patients aged 14 to 70 years with lipodystrophy will be studied: leptin naive and leptin treated. Minors will only be included in the leptin naive arm. All subjects will be stabilized on a weight maintenance diet for 5 days (Period 1). After this, leptin will be withdrawn from leptin treated subjects, and leptin will be initiated in leptin naive subjects for a period of 14 days (Period 2). The same isocaloric diet will be continued throughout both Periods, permitting study of leptin s effects independent of energy intake.
All subjects will undergo metabolic testing on admission, at the end of Period 1, and throughout Period 2, to generate a detailed short-term time course of the effects of leptin initiation or withdrawal. At the end of Period 2, leptin will be continued in the leptin naive subjects, and restarted in the leptin treated subjects. Repeat metabolic testing will be performed 6-12 months after leptin initiation in the leptin-naive cohort to generate information on leptin s long-term effects.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||None (Open Label)|
|Official Title:||Short Term Effects of Leptin Withdrawal or Initiation in Lipodystrophy Independent of Energy Intake|
|Study Start Date :||January 26, 2013|
|Estimated Primary Completion Date :||December 31, 2018|
|Estimated Study Completion Date :||December 31, 2019|
Experimental: Leptin naive
Studied for 5 days without metreleptin, then 14 days while taking metreleptin
Recombinant analog of the human hormone, leptin
Studied for 5 days while taking metreleptin, then 14 days during metreleptin withdrawal
Recombinant analog of the human hormone, leptin
- Total body insulin sensitivity [ Time Frame: 6 moths ]
- Rate of lipolysis [ Time Frame: 6 months ]
- Total 24 hour energy expenditure [ Time Frame: 6 months ]
- Fatty acid turnover, Liver & muscle triglyceride, IGFBP2; Physical activity; thyroid function; catecholamines; cardiac autonomic nervous system tone; body temperature; thermal comfort; LH pulsatility; blood pressure, hunger and satiety. [ Time Frame: 6 months ]
- Hepatic insulin sensitivity; fasting plasma glucose, C-peptide, triglycerides, resting energy expenditure; Skeletal muscle work efficiency. [ Time Frame: 6 months ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01778556
|Contact: Cristina A Meehan||(301) firstname.lastname@example.org|
|Contact: Rebecca J Brown, M.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 firstname.lastname@example.org|
|Principal Investigator:||Rebecca J Brown, M.D.||National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)|