Fatty Liver Disease, NonalcoholicPhase 2NCT00596934
Recombinant Leptin Therapy for Treatment of Nonalcoholic Steatohepatitis (NASH)
A Phase 2 study testing metreleptin in people with Fatty Liver Disease, Nonalcoholic, run by Elif Oral at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years, men only
- Conditions the study is for
- Fatty Liver Disease, Nonalcoholic
- What is being tested?
- metreleptin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2006to Mar 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Biopsy proven NASH
- Circulating fasting leptin <9 ng/mL (staggered criteria for different BMI levels)
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Nonalcoholic Steatohepatitis: is Leptin an Etiological Factor (Phase 2).
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
- Being tested
- metreleptin
- Keywords
- Nonalcoholic fatty liver disease, Insulin resistance, Obesity, Leptin therapy, NASH
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Insulin Resistance, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
metreleptinDrug
Also called (originally A100, recombinant-human-Methionyl-leptin
0.1 mg/kg/day once a day via subcutaneous injections
| Study group | Role | What they receive |
|---|---|---|
| Metreleptin treatment group | Experimental | Treatment group Receives: Drug: metreleptin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 year
Secondary outcomes (7)
Body Weight at 12 Months
Body weight (kg) after one year of treatment on metreleptin for patients that completed 12 months of metreleptin treatment.
Measured: 1 year
Liver Fat Percentage by Magnetic Resonance Imaging (MRI - Dixon Method) at 12 Months
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.
Measured: 1 year
Liver Function Test: Alanine Aminotransferase (ALT) Values at 12 Months
ALT value in subjects that completed 12 months of metreleptin treatment.
Measured: 1 year
Liver Function Test: Aspartate Aminotransferase (AST) Values at 12 Months
AST value in subjects that completed 12 months of metreleptin treatment.
Measured: 1 year
Fasting Glucose Value at 12 Months
Fasting glucose value in subjects that completed 12 months of metreleptin treatment.
Measured: 1 year
Fasting Triglycerides Value at 12 Months
Fasting triglyceride value in subjects that completed 12 months of metreleptin treatment.
Measured: 1 year
Insulin Resistance: Homeostatic Model Assessment (HOMA) at 12 Months
HOMA values in subjects that completed 12 months of metreleptin treatment.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jan 2008 (estimated)
- Study startFeb 2006
- Primary completionMar 2009
- Study completionMar 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Fatty Liver Disease, NonalcoholicStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Elif Oral
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), University of Michigan
- Responsible party
- Sponsor-investigator, Elif Oral, University of Michigan
- Investigators
- Elif A Oral, MD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00596934
- Sponsor's protocol ID
- R03DK074488
- Other IDs
- R03DK074488, Protocol 2145 (MCRU), Amylin Protocol 20050119, DRDA 643938K3
- Status last verified
- Oct 2017
- First submitted
- 8 Jan 2008
- Last updated
- 24 Nov 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 35291351
Study at a glance
From the registry record, last updated by the sponsor on 24 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nonalcoholic Steatohepatitis: is Leptin an Etiological Factor (Phase 2).
- ClinicalTrials.gov ID
- NCT00596934
- Acronym / sponsor ID
- R03DK074488
- Conditions
- Fatty Liver Disease, Nonalcoholic
- Keywords
- Nonalcoholic fatty liver disease, Insulin resistance, Obesity, Leptin therapy, NASH
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Elif OralUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), University of Michigan
- Study start
- Feb 2006
- Primary completion
- Mar 2009 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 17 Jan 2008 (estimated)
- Results
- Posted 9 Dec 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Metreleptin treatment group | Experimental | Drug: metreleptinTreatment group |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Biopsy proven NASH
- Circulating fasting leptin <9 ng/mL (staggered criteria for different BMI levels)
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| metreleptinAlso: (originally A100, recombinant-human-Methionyl-leptin0.1 mg/kg/day once a day via subcutaneous injections | Drug | Metreleptin treatment group |
Primary outcome
Non-alcoholic Steatohepatitis Score as Determined by Liver Histopathology at 12 Months
Time frame: 1 year
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.
7 secondary outcomes
Body Weight at 12 Months
Time frame: 1 year
Liver Fat Percentage by Magnetic Resonance Imaging (MRI - Dixon Method) at 12 Months
Time frame: 1 year
Liver Function Test: Alanine Aminotransferase (ALT) Values at 12 Months
Time frame: 1 year
Liver Function Test: Aspartate Aminotransferase (AST) Values at 12 Months
Time frame: 1 year
Fasting Glucose Value at 12 Months
Time frame: 1 year
Fasting Triglycerides Value at 12 Months
Time frame: 1 year
Insulin Resistance: Homeostatic Model Assessment (HOMA) at 12 Months
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Nov 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35291351Akinci 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.
- PIs Web siteLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elif A Oral, MD principal investigator
University of Michigan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing metreleptin in people with Fatty Liver Disease, Nonalcoholic, run by Elif Oral at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Dec 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Non-alcoholic Steatohepatitis Score as Determined by Liver Histopathology at 12 Months (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00596934, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Nov 2017.