Phase 2
N=25
Short-term Effects of Leptin in People With Lipodystrophy
Lipodystrophy
Bottom Line
View on ClinicalTrials.gov: NCT01778556 ↗Enrolled (actual)
25
Serious AEs
4.9%
Results posted
Nov 2019
Primary outcome: Primary: Total Body Insulin Sensitivity — 4.4; 10.9; 5.8; 6.4 mg/kg fat-free mass/min
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Metreleptin (Biological)
- Age
- Pediatric, Adult, Older Adult · 14+ yrs
- Sex
- All
- Sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Primary completion
- Feb 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Total Body Insulin Sensitivity |
4.4; 10.9; 5.8; 6.4; 8.0 | — |
| SECONDARY Insulin-mediated Suppression of Hepatic Glucose Production |
61.2; 77.1; 75.2; 63.8; 85.6 | — |
| SECONDARY Endogenous Rate of Appearance of Palmitate |
3.2; 1.4; 2.8; 1.7; 2.2 | — |
Summary
Background:
- 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.
Objectives:
- To study how leptin treatment affects lipodystrophy.
Eligibility:
- Individuals between 14 and 70 years of age who have lipodystrophy.
Design:
* 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.
Eligibility Criteria
- INCLUSION CRITERIA:
- Age 14-70 years (children under age 18 will only be enrolled in the leptin-naive arm of the study
- Clinically-significant lipodystrophy as defined in protocol 02-DK-0022 (Long Term Efficacy of Leptin Replacement in the Treatment of Lipodystrophy). Relevant inclusion criteria for enrollment in protocol 02-DK-0022 are (summarized):
- Lipodystrophy identified by the study physician during physical examination as an absence of fat outside the range of normal
- Circulating leptin levels 30 microU/mL
- Fasting hypertriglyceridemia >200 mg/dL
- Co-enrolled in protocol 02-DK-0022 and either:
- Leptin naive, with plans to initiate leptin treatment during the current study. For the purpose of this study, leptin naive will be defined as having received no exogenous leptin in the 4 months prior to study participation. Thus, subjects who previously received leptin therapy, discontinued, and wish to restart are eligible.
Or
--Leptin treated, meaning the subject has taken a stable dose of exogenous leptin for a minimum of 4 months (adults over age 18, only)
EXCLUSION CRITERIA
In leptin treated subjects only, the following exclusion criteria apply:
- Poorly controlled diabetes at study entry (hemoglobin A1c greater than or equal to 9%)
- Poorly controlled hypertriglyceridemia at study entry (serum triglycerides > 800 mg/dL)
- Extreme hypertriglyceridemia prior to leptin (triglycerides greater than 2000 mg/dL at initiation of leptin treatment)
- History of chronic or recurrent acute pancreatitis (> 1 episode), or a single episode of pancreatitis while receiving leptin treatment
- Lipase greater than the upper limit of normal (491 units/L) at study entry
In all subjects (leptin treated and leptin naive), the following exclusion criteria apply:
- Known HIV infection or HIV-associated lipodystrophy
- History of diabetic ketoacidosis
- Active inflammatory disease (e.g. dermatomyositis)
- Change in diabetes or lipid-lowering medications within the past 6 weeks
- Estimated glomerular filtration rate 4 mcIU/L) or change in thyroid medication in the past 8 weeks.
- Pregnancy or breast-feeding
- Psychiatric disorder impeding competence or compliance
- Any medical condition or medication that will increase risk to the subject (e.g. ischemic heart disease, decompensated liver disease) or that will interfere with interpretation of study data (e.g. Cushing s syndrome).
Data sourced from ClinicalTrials.gov (NCT01778556). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.