Nonalcoholic Fatty Liver DiseasePhase 4NCT01208649
Effects of Exenatide (Byetta®) on Liver Function in Patients With Nonalcoholic Steatohepatitis (NASH)
A Phase 4 study testing Exenatide in people with Nonalcoholic Fatty Liver Disease, run by Ruhr University of Bochum at 1 site in Germany.
Trial summary
The primary objective is to test the hypothesis that 24 weeks of treatment with exenatide will improve the histological acitvity of NASH (steatosis,necroinflammation, ballooning), summarized in the recently introduced NASH-score in patients with normal, impaired or diabetic glucose tolerance compared to dietary… Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Nonalcoholic Fatty Liver Disease
- What is being tested?
- Exenatide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 13 participants
- Where
- 1 siteGermany
- Study dates
- Jul 2008to Sep 2010
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age between 18 and 75 years, inclusive.
- Patients present with histologically proven non-alcoholic steatohepatitis ascertained by the single center pathologist between visit 1 and 2
- First liver biopsy was obtained not later than 6 months before visit 1
- Patients have HbA1c not exceeding 10.0%.
- Patients have a history of stable body weight (not varying by >10% for at least 3 months prior to screening
Who cannot join
- Patients are investigator site personnel directly affiliated with the study, or are immediate family of investigator site personnel directly affiliated with the study. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
- Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods (adequate contraceptive measures include sterilisation, hormonal intrauterine devices, oral contraceptives, sexual abstinence or vasectomised partner). A male subject who is sexually active and has not been surgically sterilised must be informed that he must either use a condom during intercourse, ensure that his partner practices contraception, or he must refrain from sexual intercourse during the trial and until 1 month after completion of the trial. This is to prevent the possibility of a pregnancy from spermatocytes that can potentially be damaged by trial medication. It is strongly recommended that the female partners use a highly effective contraception (Pearl Index < 1%).
- Patients have participated in an interventional medical, surgical, or pharmaceutical study (a study in which an experimental, drug, medical, or surgical treatment was given) within 30 days prior to screening. This criterion includes drugs that have not received regulatory approval for any indication at the time of study entry.
- Patients with evidence of viral or autoimmune hepatitis (positive testing for HBsAG, anti-HCV or anti-HIV, pos. AMA-screen, ANA-titer > 1:160)
- Patients with inherited liver diseases (e.g. Wilson's disease, Hemochromatosis)
- Patients have alcohol consumption (>20 g daily for males and >10 g daily for females)
Show all 19Show fewer
- Patients have decompensated liver cirrhosis (Child-Pugh score >7)
- Patients have alanine aminotransaminase (ALT) greater than ten times the upper limit of the reference range.
- Patients have had greater than three episodes of severe hypoglycemia within 6 months prior to screening.
- Patients are undergoing therapy for a malignancy, other than basal cell or squamous cell skin cancer.
- Patients have cardiac disease that is Class III or IV, according to the New York Heart Association criteria.
- Patients have a known allergy or hypersensitivity to exenatide, or excipients contained in these agents.
- Patients have or had concomitant medication with thiazolidinediones.
- Patients have a history of renal transplantation or are currently receiving renal dialysis or have serum creatinine >1.8 mg/dL for males and greater than or equal to >1.5 mg/dL for females.
- Patients have known hemoglobinopathy or chronic anemia
- Patients are receiving chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy (excluding topical and inhaled preparations) or have received such therapy within 2 weeks immediately prior to screening.
- Patients have used any prescription drug to promote weight loss within 3 months prior to screening.
- Patients have any other condition (including known drug or alcohol abuse or psychiatric disorder) that precludes them from following and completing the protocol, in the opinion of the investigator.
- Patients fail to satisfy the investigator of suitability to participate for any other reason.
Trial locations and contacts
1 site in 1 country.
Germany1 site
Department of Medicine I; University Hospital St. Josef-Hospital
Bochum, 44791
About this study
Official title: Effects of Exenatide (Byetta®) on Biochemical and Histological Parameters of Liver Function in Patients With Nonalcoholic Steatohepatitis (NASH)
The primary objective is to test the hypothesis that 24 weeks of treatment with exenatide will improve the histological acitvity of NASH (steatosis,necroinflammation, ballooning), summarized in the recently introduced NASH-score in patients with normal, impaired or diabetic glucose tolerance compared to dietary guidance alone.
Read the detailed description
Non alcoholic steatohepatitis (NASH), a chronic liver disease characterized by insulin resistance, accumulation of hepatic fat and hepatocellular necroinflammation, has been recognized as a leading cause of (cryptogenic) liver cirrhosis in developed countries. Given the rising prevalence of NASH and the associated socio-economic burden associated, novel therapeutic options are warranted. The incretin mimetic Exenatide (Byetta®) exhibits strong glucoregulatory activities through its multiple biological effects. In addition, exenatide treatment has been shown to improve lipid homeostasis and reduce body weight. Since the development of NASH has been tightly linked to the presence of obesity, hyperlipidaemia and diabetes, this study will examine, whether 24 weeks of treatment with exenatide will also result in improvements in liver function in patients with NASH.
60 patients with histologically proven NASH will be randomized to receive either exenatide (2 x 5 µg s.c. for 4 weeks, 2 x 10 µg thereafter) or placebo treatment, in a 1:1 ratio. Liver biopsies will be performed after 24 weeks of treatment. In addition, a non-invasive assessment of hepatic mitochondrial function will be carried-out using a 13C-methionine breath test at baseline, and at weeks 12 and 24. Insulin sensitivity and glucose tolerance will be assessed by a hyperinsulinaemic-euglycaemic clamp (baseline and week 24) and an oral glucose tolerance test (baseline, weeks 12 and 24). Hepatic fat content will be measured by magnetic resonance tomography. Liver enzymes will be monitored closely throughout the study period.
These studies will clarify whether exenatide treatment, in addition to its beneficial effects on glucose homeostasis and body weight, will also result in improvements of liver function in patients with NASH.
- Conditions
- Nonalcoholic Fatty Liver Disease
- Being tested
- Exenatide
- Keywords
- exenatide, hepatic steatosis, insulin resistance, insulin sensitizers, nonalcoholic fatty liver disease, - GLP1-Analog
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Fatty Liver, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ExenatideDrug
Exenatide; 48 weeks 10 microg injection s.c., twice daily, before the morning and evening meal with a four week wash-in phase with 5 microg injection s.c.twice daily
| Study group | Role | What they receive |
|---|---|---|
| Exenatide | Active comparator | Drug (including placebo) Receives: Drug: Exenatide |
| Placebo | Placebo comparator | Not described Receives: Drug: Exenatide |
What is being measured
The primary outcome is the main question the study is designed to answer.
histological activity of NASH (steatosis, necroinflammation, ballooning)
Measured: 24 weeks
Secondary outcomes (1)
Liver fibrosis, as determined using the fibrosis score
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2010 (estimated)
- Study startJul 2008
- Primary completionSep 2010
- Study completionSep 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nonalcoholic Fatty Liver DiseaseStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ruhr University of Bochum
- Sponsor type
- University, hospital or other
- Investigators
- Wolfgang E. Schmidt, Prof. Dr., Study director, Ruhr-University BochumWolfgang E. Schmidt, Prof. Dr., Principal investigator, Ruhr-University Bochum
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01208649
- Sponsor's protocol ID
- H80-MC-O008
- Status last verified
- Sep 2010
- First submitted
- 23 Sep 2010
- Last updated
- 24 Sep 2010
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Exenatide (Byetta®) on Biochemical and Histological Parameters of Liver Function in Patients With Nonalcoholic Steatohepatitis (NASH)
- ClinicalTrials.gov ID
- NCT01208649
- Acronym / sponsor ID
- H80-MC-O008
- Conditions
- Nonalcoholic Fatty Liver Disease
- Keywords
- exenatide, hepatic steatosis, insulin resistance, insulin sensitizers, nonalcoholic fatty liver disease, - GLP1-Analog
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Ruhr University of BochumUniversity, hospital or other
- Study start
- Jul 2008
- Primary completion
- Sep 2010 (actual)
- Study completion
- Sep 2010 (actual)
- First posted
- 24 Sep 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective is to test the hypothesis that 24 weeks of treatment with exenatide will improve the histological acitvity of NASH (steatosis,necroinflammation, ballooning), summarized in the recently introduced NASH-score in patients with normal, impaired or diabetic glucose tolerance compared to dietary guidance alone.
Detailed description
Non alcoholic steatohepatitis (NASH), a chronic liver disease characterized by insulin resistance, accumulation of hepatic fat and hepatocellular necroinflammation, has been recognized as a leading cause of (cryptogenic) liver cirrhosis in developed countries. Given the rising prevalence of NASH and the associated socio-economic burden associated, novel therapeutic options are warranted. The incretin mimetic Exenatide (Byetta®) exhibits strong glucoregulatory activities through its multiple biological effects. In addition, exenatide treatment has been shown to improve lipid homeostasis and reduce body weight. Since the development of NASH has been tightly linked to the presence of obesity, hyperlipidaemia and diabetes, this study will examine, whether 24 weeks of treatment with exenatide will also result in improvements in liver function in patients with NASH.
60 patients with histologically proven NASH will be randomized to receive either exenatide (2 x 5 µg s.c. for 4 weeks, 2 x 10 µg thereafter) or placebo treatment, in a 1:1 ratio. Liver biopsies will be performed after 24 weeks of treatment. In addition, a non-invasive assessment of hepatic mitochondrial function will be carried-out using a 13C-methionine breath test at baseline, and at weeks 12 and 24. Insulin sensitivity and glucose tolerance will be assessed by a hyperinsulinaemic-euglycaemic clamp (baseline and week 24) and an oral glucose tolerance test (baseline, weeks 12 and 24). Hepatic fat content will be measured by magnetic resonance tomography. Liver enzymes will be monitored closely throughout the study period.
These studies will clarify whether exenatide treatment, in addition to its beneficial effects on glucose homeostasis and body weight, will also result in improvements of liver function in patients with NASH.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Exenatide | Active comparator | Drug: ExenatideDrug (including placebo) |
| Placebo | Placebo comparator | Drug: Exenatide |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age between 18 and 75 years, inclusive.
- Patients present with histologically proven non-alcoholic steatohepatitis ascertained by the single center pathologist between visit 1 and 2
- First liver biopsy was obtained not later than 6 months before visit 1
- Patients have HbA1c not exceeding 10.0%.
- Patients have a history of stable body weight (not varying by >10% for at least 3 months prior to screening
Key exclusion criteria (19 listed)
- Patients are investigator site personnel directly affiliated with the study, or are immediate family of investigator site personnel directly affiliated with the study. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
- Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods (adequate contraceptive measures include sterilisation, hormonal intrauterine devices, oral contraceptives, sexual abstinence or vasectomised partner). A male subject who is sexually active and has not been surgically sterilised must be informed that he must either use a condom during intercourse, ensure that his partner practices contraception, or he must refrain from sexual intercourse during the trial and until 1 month after completion of the trial. This is to prevent the possibility of a pregnancy from spermatocytes that can potentially be damaged by trial medication. It is strongly recommended that the female partners use a highly effective contraception (Pearl Index < 1%).
- Patients have participated in an interventional medical, surgical, or pharmaceutical study (a study in which an experimental, drug, medical, or surgical treatment was given) within 30 days prior to screening. This criterion includes drugs that have not received regulatory approval for any indication at the time of study entry.
- Patients with evidence of viral or autoimmune hepatitis (positive testing for HBsAG, anti-HCV or anti-HIV, pos. AMA-screen, ANA-titer > 1:160)
- Patients with inherited liver diseases (e.g. Wilson's disease, Hemochromatosis)
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 |
|---|---|---|
| ExenatideExenatide; 48 weeks 10 microg injection s.c., twice daily, before the morning and evening meal with a four week wash-in phase with 5 microg injection s.c.twice daily | Drug | Exenatide, Placebo |
Primary outcome
histological activity of NASH (steatosis, necroinflammation, ballooning)
Time frame: 24 weeks
1 secondary outcome
Liver fibrosis, as determined using the fibrosis score
Time frame: 24 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2010.
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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.
Wolfgang E. Schmidt, Prof. Dr. study director
Ruhr-University Bochum
Wolfgang E. Schmidt, Prof. Dr. principal investigator
Ruhr-University Bochum
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Exenatide in people with Nonalcoholic Fatty Liver Disease, run by Ruhr University of Bochum at 1 site in Germany.
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 5 inclusion and 19 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 Sep 2010. 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 Germany. 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. Some participants in this study may receive a placebo. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
histological activity of NASH (steatosis, necroinflammation, ballooning) (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Sep 2010.