NCT01679197

Clinical Protocol to Investigate the Efficacy of Recombinant Human Leptin (Metreleptin) in Nonalcoholic Steatohepatitis (NASH) or Nonalcoholic Fatty Liver Disease (NAFLD) Associated With Lipodystrophy

Completed Phase 2 Results posted Last updated 14 June 2017

What this trial tests

Phase 2 trial testing Metreleptin in Fatty Liver Disease, Nonalcoholic in 23 participants. Completed in 13 July 2016.

Timeline

8 October 2012

Primary endpoint
13 July 2016

13 July 2016

Quick facts

Lead sponsor	University of Michigan
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	23
Start date	8 October 2012
Primary completion	13 July 2016
Estimated completion	13 July 2016
Sites	1 location across United States

Drugs / interventions tested

• Metreleptin (METRELEPTIN) — full drug profile →

Conditions studied

• Fatty Liver Disease, Nonalcoholic — all drugs for Fatty Liver Disease, Nonalcoholic →
• Nonalcoholic Steatohepatitis — all drugs for Nonalcoholic Steatohepatitis →
• Lipodystrophy — all drugs for Lipodystrophy →

Sponsor

University of Michigan

Who can join

5 and older, any sex, with Fatty Liver Disease, Nonalcoholic or Nonalcoholic Steatohepatitis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Liver Histopathology Primary · 1 year

Primary outcome will be the total non-alcoholic steatohepatitis (NASH) score read histopathologically from the liver biopsy samples. This outcome measure quantifies the severity of fatty liver disease. At baseline and at the end of the year, patients have undergone a transcutaneous liver biopsy and the specimens were graded for the severity of non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) pathology. Histological features of NAFLD/NASH were scored using the validated NASH-CRN (NASH Clinical Research Network) scoring system. This scoring system is the total of 4

Baseline

Group	Value	95% CI
Treatment	6	± 2

Month 12

Group	Value	95% CI
Treatment	5	± 2

Liver Fat by MRI and MR Spectroscopy Secondary · 1 year

All enrolled patients will have a baseline MRI of the liver to evaluate liver volume and liver fat. For determination of hepatic fat content by MRI and MR spectroscopy in patients, a series of out-phase and in-phase MRI at multiple flip angles are used. By combination of out-phase and in-phase MRI at multiple flip-angles and TE times, relaxation-time effects can be removed to yield quantitative intra-hepatic (and other organs') fractional fat content throughout the liver in a few breath-hold intervals.

Baseline

Group	Value	95% CI
Treatment	19.19	± 11.11

Month 12

Group	Value	95% CI
Treatment	13.47	± 9.02

Liver Function Tests Secondary · 1 year

AST and ALT are the liver function tests. We are reporting the liver function tests where the treatment group arm would normally be listed, though, we are looking at the same single arm population of 23 participants who received treatment in this study.

Baseline

Group	Value	95% CI
Liver Function AST	41.52	± 27.46
Liver Function ALT	53.22	± 37.03

Month 12

Group	Value	95% CI
Liver Function AST	30.37	± 14.04
Liver Function ALT	36	± 22.84

Fasting Lipids Secondary · 1 year

Cholesterol, triglycerides, HDL cholesterol, and LDL together make up the lipid profile and must be reported together. We are reporting the lipid profile where the treatment group arm would normally be listed, though, we are looking at the same single arm population of 23 participants who received treatment in this study.

Baseline

Group	Value	95% CI
Cholesterol, Total mg/dL	256.91	± 136.87
Triglycerides mg/dL	1057.48	± 1744.89
HDL Cholesterol mg/dL	35.83	± 11.01
LDL mg/dL	95.39	± 48.30

Month 12

Group	Value	95% CI
Cholesterol, Total mg/dL	189.11	± 64.73
Triglycerides mg/dL	478.47	± 790.85
HDL Cholesterol mg/dL	33.42	± 6.41
LDL mg/dL	95.95	± 32.64

Fasting Glucose Secondary · 1 year

Baseline

Group	Value	95% CI
Treatment	178.91	± 82.36

Month 12

Group	Value	95% CI
Treatment	163.53	± 66.79

Body Weight Secondary · 1 year

Baseline

Group	Value	95% CI
Treatment	77.2	± 21.4

Month 12

Group	Value	95% CI
Treatment	75.0	± 23.1

Adverse events — posted to ClinicalTrials.gov

Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Treatment

Serious: 7/23 (30%)

Deaths: 0/23

Serious adverse events (12 terms)

Reaction	System	Treatment
Left shoulder pain, atypical chest pain	Cardiac disorders	—
Granulomatous tissue reaction	Immune system disorders	—
Bronchial pneumonia	Respiratory, thoracic and mediastinal disorders	—
Fall, hip fracture	Musculoskeletal and connective tissue disorders	—
Hypertriglyceridemia	Metabolism and nutrition disorders	—
Transient ischemic attack vs. cerebrovascular attack vs. complicated migraine	Nervous system disorders	—
Epigastric pain, mild chest pain	Gastrointestinal disorders	—
Secondary diabetes mellitus with keatoacidosis	Metabolism and nutrition disorders	—
Bell's palsy left side weakness	Nervous system disorders	—
UTI abdominal pain	Renal and urinary disorders	—
Rectal prolapse surgery	Surgical and medical procedures	—
Chest pain	Musculoskeletal and connective tissue disorders	—

Other adverse events (18 terms — click to expand)

Reaction	System	Treatment
Upper respiratory tract infection	Immune system disorders	—
Hypoglycemia	Blood and lymphatic system disorders	—
Diarrhea	Gastrointestinal disorders	—
Cold/Flu-like symptoms	Infections and infestations	—
Nausea	General disorders	—
Asthma	Respiratory, thoracic and mediastinal disorders	—
Abdominal pain/discomfort	Gastrointestinal disorders	—
Injection site reaction	Skin and subcutaneous tissue disorders	—
Muscle cramping	Musculoskeletal and connective tissue disorders	—
Dizziness	General disorders	—
Urinary tract infection	Renal and urinary disorders	—
Fall	Musculoskeletal and connective tissue disorders	—
Alopecia	Skin and subcutaneous tissue disorders	—
Bronchitis	Respiratory, thoracic and mediastinal disorders	—
Vomiting	Gastrointestinal disorders	—
Hematuria	Renal and urinary disorders	—
Cough	Respiratory, thoracic and mediastinal disorders	—
Rash	Skin and subcutaneous tissue disorders	—

Most-reported serious reactions: Left shoulder pain, atypical chest pain, Granulomatous tissue reaction, Bronchial pneumonia, Fall, hip fracture, Hypertriglyceridemia, Transient ischemic attack vs. cerebrovascular attack vs. complicated migraine, Epigastric pain, mild chest pain, Secondary diabetes mellitus with keatoacidosis.

Data from ClinicalTrials.gov NCT01679197 adverse events section.

Sponsor's own description

This study involves research about an investigational medicine called metreleptin. The reason for this study is to find out how metreleptin can improve non-alcoholic steatohepatitis or nonalcoholic fatty liver disease associated with lipodystrophy, a rare disorder associated with abnormal loss of the body's fat tissue. In this study, metreleptin is considered to be investigational for the treatment of lipodystrophy. Metreleptin will be 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 (e.g. blood cholesterol, liver function, insulin resistance) and body composition characteristics (e.g. the pattern of fat distribution in the body).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Leptin's role in lipodystrophic and nonlipodystrophic insulin-resistant and diabetic individuals.
   Moon HS, Dalamaga M, Kim SY, Polyzos SA, et al · · 2013 · cited 179× · PMID 23475416 · DOI 10.1210/er.2012-1053
2. Spectrum of disease associated with partial lipodystrophy: lessons from a trial cohort.
   Ajluni N, Meral R, Neidert AH, Brady GF, et al · · 2017 · cited 86× · PMID 28199729 · DOI 10.1111/cen.13311
3. Association of Adipose Tissue and Adipokines with Development of Obesity-Induced Liver Cancer.
   Rajesh Y, Sarkar D. · · 2021 · cited 47× · PMID 33671547 · DOI 10.3390/ijms22042163
4. Metreleptin therapy for nonalcoholic steatohepatitis: Open-label therapy interventions in two different clinical settings.
   Akinci B, Subauste A, Ajluni N, Esfandiari NH, et al · · 2021 · cited 26× · PMID 35291351 · DOI 10.1016/j.medj.2021.04.001
5. Endogenous Leptin Concentrations Poorly Predict Metreleptin Response in Patients With Partial Lipodystrophy.
   Meral R, Malandrino N, Walter M, Neidert AH, et al · · 2022 · cited 16× · PMID 34677608 · DOI 10.1210/clinem/dgab760
6. Metabolic Improvements With Tirzepatide in Lipodystrophy: A Novel Option?
   Meral R, Celik Guler M, Kaba D, Prativadi J, et al · · 2025 · cited 10× · PMID 40063619 · DOI 10.2337/dc24-2408
7. The complicated clinical course in a case of atypical lipodystrophy after development of neutralizing antibody to metreleptin: treatment with setmelanotide.
   Akinci B, Meral R, Rus D, Hench R, et al · · 2020 · cited 7× · PMID 32213649 · DOI 10.1530/edm-19-0139
8. Efficacy and Safety of Obeticholic Acid for Treating Hepatic Steatosis in Patients With Familial Partial Lipodystrophy.
   Garg A, Vasandani C, Li X, Quittner C, et al · · 2025 · cited 2× · PMID 40080694 · DOI 10.1210/clinem/dgaf173