Hypoleptinemia, Generalized Lipodystrophy, Partial Lipodystrophy, Insulin Resistance
Conditions
Keywords
Lipodystrophy, Insulin secretory response
Brief summary
Lipodystrophies represent a therapeutic challenge with regards to insulin resistance, hypertriglyceridemia and fatty liver which often is coupled with significant adipose tissue loss. The purpose of the study is to examine the safety and efficacy of Leptin on subjects with lipodystrophy.
Detailed description
The mechanism by which leptin improves glucose and lipid control is not clear. We will examine the possible mechanisms of leptin action by studying the effects of leptin administration on food intake, insulin resistance, insulin secretory response, hepatic and intramuscular triglyceride stores in a large sample of patients with lipodystrophy. Hypothesis: Leptin replacement in patients with generalized and partial lipodystrophy and hypoleptinemia will be safe and efficacious in improving the metabolic abnormalities associated with insulin resistance.
Interventions
DRUGLeptin
Leptin injected subcutaneously twice a day, to be administered at 100% of the estimated replacement dose during the first month, which is a dosage of 0.03mg/kg for female children, 0.04mg/kg for adult females, and0.02 mg/kg for all males, and then at 200% subsequently, or placebo.
DRUGPlacebo
Sugar pill
Sponsors
University of Texas Southwestern Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* age \> 6 years * Partial and generalized lipodystrophy * Serum leptin levels less than the 7th percentile of normal values reported by the 3rd National Health and Nutrition Examination survey (less than 7.0 ng/mL in females and less than 3/0 ng/mL in males) * Presence of at least one of the following metabolic abnormalities: 1. Type 2 Diabetes Mellitus 2. Fasting serum insulin \>20 uU/mL 3. Fasting serum triglycerides \> 300 mg/dL 4. Previous participation in leptin trial (Amgen 991265, GCRC 660) - for Part B of the Study.
Exclusion criteria
* Known liver disease due to causes other than non-alcoholic steatohepatitis. * Hematocrit of less than 30%. * Current alcohol or substance abuse. * Use of anorexigenic drugs, anabolic steroids, GH and thiazolidinediones * Active tuberculosis * Psychiatric disorder impeding competence or compliance * Malignancies * HIV infection * Subjects who have a known hypersensitivity to E. Coli derived proteins * Other condition, which in the opinion of the clinical investigators would impede completion of the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Fasting Serum Triglycerides | 4 months |
| HbA1c | 4 months |
Secondary
| Measure | Time frame |
|---|---|
| Fasting Serum Glucose | 4 months |
| Body Weight | 4 months |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Leptin Therapy Participants were randomized to receive Leptin . | 13 |
| Placebo Participants were randomized to receive Placebo . | 12 |
| Total | 25 |
Baseline characteristics
| Characteristic | Leptin Therapy | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 27.2 years STANDARD_DEVIATION 11.9 | 24.9 years STANDARD_DEVIATION 13 | 26.1 years STANDARD_DEVIATION 12.2 |
| Body weight | 65.5 kg STANDARD_DEVIATION 17.5 | 57.7 kg STANDARD_DEVIATION 16 | 61.8 kg STANDARD_DEVIATION 16.9 |
| Fasting serum Glucose | 157.0 mg/dL STANDARD_DEVIATION 74.2 | 184.0 mg/dL STANDARD_DEVIATION 87.2 | 170.0 mg/dL STANDARD_DEVIATION 80.2 |
| Fasting serum Triglycerides | 309.3 mg/dL | 443.8 mg/dL | 309.3 mg/dL |
| HbA1c | 8.1 % of haemoglobin STANDARD_DEVIATION 2.5 | 8.0 % of haemoglobin STANDARD_DEVIATION 2.5 | 8.0 % of haemoglobin STANDARD_DEVIATION 2.5 |
| Sex: Female, Male Female | 10 Participants | 9 Participants | 19 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 12 |
| other Total, other adverse events | 2 / 13 | 4 / 12 |
| serious Total, serious adverse events | 0 / 13 | 0 / 12 |
Outcome results
Primary
Fasting Serum Triglycerides
Time frame: 4 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Leptin Therapy | Fasting Serum Triglycerides | 203 mg/dL |
| Placebo | Fasting Serum Triglycerides | 304 mg/dL |
p-value: 0.2572Mixed Models Analysis
Primary
HbA1c
Time frame: 4 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Leptin Therapy | HbA1c | 8.1 % of haemoglobin |
| Placebo | HbA1c | 7.6 % of haemoglobin |
p-value: 0.71Mixed Models Analysis
Secondary
Body Weight
Time frame: 4 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Leptin Therapy | Body Weight | 62.5 kg | Standard Deviation 17.5 |
| Placebo | Body Weight | 56.3 kg | Standard Deviation 17.6 |
p-value: 0.0256Mixed Models Analysis
Secondary
Fasting Serum Glucose
Time frame: 4 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Leptin Therapy | Fasting Serum Glucose | 162 mg/dL |
| Placebo | Fasting Serum Glucose | 165 mg/dL |
p-value: 0.68Mixed Models Analysis