Phase 2
N=9
Recombinant Leptin Therapy for Treatment of Nonalcoholic Steatohepatitis (NASH)
Fatty Liver Disease, Nonalcoholic
Bottom Line
View on ClinicalTrials.gov: NCT00596934 ↗Enrolled (actual)
9
Serious AEs
11.1%
Results posted
Dec 2016
Primary outcome: Primary: Non-alcoholic Steatohepatitis Score as Determined by Liver Histopathology at 12 Months — 5 units on a scale — p=0.015
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- metreleptin (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- Male
- Sponsor
- Elif Oral
- Primary completion
- Mar 2009
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Non-alcoholic Steatohepatitis Score as Determined by Liver Histopathology at 12 Months |
5 | 0.015 sig |
| SECONDARY Body Weight at 12 Months |
86.4 | <0.0001 sig |
| SECONDARY Liver Fat Percentage by Magnetic Resonance Imaging (MRI - Dixon Method) at 12 Months |
13.7 | 0.074 |
| SECONDARY Liver Function Test: Alanine Aminotransferase (ALT) Values at 12 Months |
44.3 | 0.003 sig |
| SECONDARY Liver Function Test: Aspartate Aminotransferase (AST) Values at 12 Months |
34.9 | 0.006 sig |
| SECONDARY Fasting Glucose Value at 12 Months |
92.1 | 0.023 sig |
| SECONDARY Fasting Triglycerides Value at 12 Months |
146.4 | 0.195 |
| SECONDARY Insulin Resistance: Homeostatic Model Assessment (HOMA) at 12 Months |
4.1 | 0.026 sig |
Summary
Nonalcoholic steatohepatitis (or NASH) is known to be caused by deposition of fat in the liver and development of scarring. This condition occurs more frequently in overweight and obese persons. It is often associated with resistance to the actions of insulin hormone. Fat cells secrete a hormone called leptin. Recently, we have learned that obese or overweight persons make too much leptin, which may contribute to insulin resistance. Paradoxically, patients who do not have any fat cells, also have insulin resistance. In these patients, insulin resistance is caused by the absence of leptin and leptin replacement significantly improves insulin resistance and fat deposition in the liver. In an earlier study, we determined the leptin levels in patients with NASH and how these levels are related to body fat levels as well as responsiveness to insulin. We saw that a subgroup of patients with NASH have relatively low levels of leptin in contrast to the amount of body fat they had. We now would like to see if restoring leptin levels to normal will improve the disease process in these patients. Our study patients will be male patients, aged between 18 and 65 (inclusive), who do not have any other cause for their liver disease. We have put some restrictions in body size such that a spectrum of patients from normal weight to obese range would be included. They will also demonstrate low leptin levels (levels similar to only 25% of normal population). We will use a genetically engineered form of leptin manufactured by Amylin Inc. given via injections under the skin. We plan to continue therapy for a period of one year and evaluate the change in liver disease by a liver biopsy. We will also follow the metabolic parameters and body composition characteristics that we examined in our earlier study. We expect that patients with low blood leptin levels will show improvement in their liver disease and insulin resistance when their blood leptin levels are restored to normal.
Eligibility Criteria
Inclusion Criteria
- Biopsy proven NASH
- Circulating fasting leptin 126 mg/dL or 2 hour post 75 g-glucose >200 mg/dL or random glucose >200 mg/dL with presence of diabetes symptoms or known history of diabetes)
- Any medication for treatment of NASH or obesity
- Presence of HIV
- Inability to give informed consent
- Presence of end-stage renal disease, any type of active cancer, or >class 2 congestive heart failure ((New York Heart Association Functional Classification System), based on medical history and physical examination
- Presence of any other condition that limits life expectancy to <2 years
- Active infection (may be transient)
- Any other condition in the opinion of the investigators that may impede successful data collection
Data sourced from ClinicalTrials.gov (NCT00596934). 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.