Recombinant Leptin Therapy for Treatment of Nonalcoholic Steatohepatitis (NASH)

NCT ID: NCT00596934

Last Updated: 2017-11-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-02-28
• Study Completion Date: 2009-03-31

Brief 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.

Conditions

Fatty Liver Disease, Nonalcoholic

Keywords

Nonalcoholic fatty liver disease; Insulin resistance; Obesity; Leptin therapy; NASH

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Metreleptin treatment group

Treatment group

Group Type: EXPERIMENTAL

metreleptin

Intervention Type: DRUG

0.1 mg/kg/day once a day via subcutaneous injections

Interventions

metreleptin

0.1 mg/kg/day once a day via subcutaneous injections

Intervention Type: DRUG

Other Intervention Names

(originally A100, recombinant-human-Methionyl-leptin

Eligibility Criteria

Inclusion Criteria

• Biopsy proven NASH
• Circulating fasting leptin <9 ng/mL (staggered criteria for different BMI levels)

Exclusion Criteria

• Presence of advanced liver disease (as evidenced by abnormal synthetic function, abnormal prothrombin time or albumin)
• Presence of clinical lipodystrophy
• Presence of other liver disease
• Presence of clinical diabetes (fasting >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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

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

NIH

Sponsor Role: collaborator

University of Michigan

OTHER

Sponsor Role: collaborator

Elif Oral

OTHER

Sponsor Role: lead

Responsible Party

Elif Oral

Associate Prof of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Elif A Oral, MD

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Locations

University of Michigan

Ann Arbor, Michigan, United States

Countries

United States

References

Akinci B, Subauste A, Ajluni N, Esfandiari NH, Meral R, Neidert AH, Eraslan A, Hench R, Rus D, McKenna B, Hussain HK, Chenevert TL, Tayeh MK, Rupani AR, Innis JW, Mantzoros CS, Conjeevaram HS, Burant CL, Oral EA. Metreleptin therapy for nonalcoholic steatohepatitis: Open-label therapy interventions in two different clinical settings. Med. 2021 Jul 9;2(7):814-835. doi: 10.1016/j.medj.2021.04.001. Epub 2021 May 12.

Reference Type: DERIVED

PMID: 35291351 (View on PubMed)

Related Links

http://www.uofmhealth.org/profile/83/elif-oral-md

PIs Web site

Other Identifiers

R03DK074488

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Protocol 2145 (MCRU)

Identifier Type: -

Identifier Source: secondary_id

Amylin Protocol 20050119

Identifier Type: -

Identifier Source: secondary_id

DRDA 643938K3

Identifier Type: -

Identifier Source: secondary_id

R03DK074488

Identifier Type: NIH

Identifier Source: org_study_id

View Link