NCT00596934

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
9

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Feb 2006

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2006

Completed
1.9 years until next milestone

First Submitted

Initial submission to the registry

January 8, 2008

Completed
9 days until next milestone

First Posted

Study publicly available on registry

January 17, 2008

Completed
1.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2009

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2009

Completed
7.8 years until next milestone

Results Posted

Study results publicly available

December 9, 2016

Completed
Last Updated

November 24, 2017

Status Verified

October 1, 2017

Enrollment Period

3.1 years

First QC Date

January 8, 2008

Results QC Date

August 22, 2016

Last Update Submit

October 19, 2017

Conditions

Fatty Liver Disease, Nonalcoholic

Keywords

Nonalcoholic fatty liver diseaseInsulin resistanceObesityLeptin therapyNASH

Outcome Measures

Primary Outcomes (1)

  • Non-alcoholic Steatohepatitis Score as Determined by Liver Histopathology at 12 Months

    Non-alcoholic steatohepatitis (NASH) score after approximately one year of treatment with metreleptin. Total NASH scores can range from 0 to 14. The higher the NASH score the more severe the liver disease.

    1 year

Secondary Outcomes (7)

  • Body Weight at 12 Months

    1 year

  • Liver Fat Percentage by Magnetic Resonance Imaging (MRI - Dixon Method) at 12 Months

    1 year

  • Liver Function Test: Alanine Aminotransferase (ALT) Values at 12 Months

    1 year

  • Liver Function Test: Aspartate Aminotransferase (AST) Values at 12 Months

    1 year

  • Fasting Glucose Value at 12 Months

    1 year

  • +2 more secondary outcomes

Study Arms (1)

Metreleptin treatment group

EXPERIMENTAL

Treatment group

Drug: metreleptin

Interventions

metreleptinDRUG

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

Also known as: (originally A100, recombinant-human-Methionyl-leptin
Metreleptin treatment group

Eligibility Criteria

Age18 Years - 65 Years
Sexmale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Related Publications (1)

  • 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.

    PMID: 35291351DERIVED

Related Links

MeSH Terms

Conditions

Non-alcoholic Fatty Liver DiseaseInsulin ResistanceObesity

Interventions

metreleptinrecombinant methionyl human leptin

Condition Hierarchy (Ancestors)

Fatty LiverLiver DiseasesDigestive System DiseasesHyperinsulinismGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesOverweightOvernutritionNutrition DisordersBody WeightSigns and SymptomsPathological Conditions, Signs and Symptoms

Limitations and Caveats

This is a non-blinded, non-placebo controlled proof of concept trial. Out of the 9 patients, there were 7 completers.

Results Point of Contact

Title
Dr. Elif A. Oral
Organization
University of Michigan
eliforal@med.umich.edu
734-615-7271

Study Officials

  • Elif A Oral, MD

    University of Michigan

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Associate Prof of Medicine

Study Record Dates

First Submitted

January 8, 2008

First Posted

January 17, 2008

Study Start

February 1, 2006

Primary Completion

March 1, 2009

Study Completion

March 1, 2009

Last Updated

November 24, 2017

Results First Posted

December 9, 2016

Record last verified: 2017-10

Locations

US(1)