Non-alcoholic Fatty Liver DiseasePhase 2NCT01963845
Sitagliptin Versus Placebo in the Treatment of Non-alcoholic Fatty Liver Disease
A Phase 2 study testing Sitagliptin in people with Non-alcoholic Fatty Liver Disease, run by University of California, San Diego at 1 site in United States.
Trial summary
Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of diseases ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), the progressive form of liver disease that can lead to cirrhosis and liver-related mortality in persons who drink little or no alcohol. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Non-alcoholic Fatty Liver Disease
- What is being tested?
- Sitagliptin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2014to Jan 2016
- 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 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age at entry at least 18 years.
- Serum alanine (ALT) or aspartate (AST) aminotransferase activities that are above the upper limits of normal. 19 or more in women and 30 or more in men.
- Evidence of hepatic steatosis or liver fat (≥5%) by MRI.
- Prediabetic patients and controlled diabetic patients as defined by the ADA position statement on diabetes mellitus. Prediabetics have a HbA1c of 5.7 to 6.4 and controlled diabetic patients have an HbA1c between 6.4 and 8.0.
- Written informed consent.
Who cannot join
- Uncontrolled diabetes defined as a Hb A1c ≥ 8.0.
- Evidence of another form of liver disease.
- Hepatitis B as defined as presence of hepatitis B surface antigen (HBsAg).
- Hepatitis C as defined by presence of hepatitis C virus (HCV) RNA in serum.
- Autoimmune hepatitis as defined by anti-nuclear antibody (ANA) of 1:160 or greater and liver histology consistent with autoimmune hepatitis or previous response to immunosuppressive therapy.
- Autoimmune cholestatic liver disorders as defined by elevation of alkaline phosphatase and anti-mitochondrial antibody of greater than 1:80 or liver histology consistent with primary biliary cirrhosis or elevation of alkaline phosphatase and liver histology consistent with sclerosing cholangitis.
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- Wilson disease as defined by ceruloplasmin below the limits of normal and liver histology consistent with Wilson disease.
- Alpha-1-antitrypsin deficiency as defined by alpha-1-antitrypsin level less than normal and liver histology consistent with alpha-1-antitrypsin deficiency.
- Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D.
- Drug-induced liver disease as defined on the basis of typical exposure and history.
- Bile duct obstruction as shown by imaging studies.
- History of excess alcohol ingestion, averaging more than 30 gm/day (3 drinks per day) in the previous 10 years, or history of alcohol intake averaging greater than 10 gm/day (1 drink per day: 7 drinks per week) in the previous one year.
- Advanced liver disease: platelet counts < 75,000/mm3 or prothrombin time >16 seconds or history of bleeding disorders
- Decompensated liver disease, Child-Pugh score greater than or equal to 7 points
- History of gastrointestinal bypass surgery or ingestion of drugs known to produce hepatic steatosis including corticosteroids, high-dose estrogens, methotrexate, tetracycline or amiodarone in the previous 6 months.
- Recent initiation or change of anti-diabetic drugs, including insulin, sulfonylureas, or thiazolidinediones in the previous 90 days.
- Use of sitagliptin or other agents in the same class within the 90 days prior to randomization.
- Significant systemic or major illnesses other than liver disease, including congestive heart failure, coronary artery disease, cerebrovascular disease, pulmonary disease with hypoxia, renal failure, organ transplantation, serious psychiatric disease, malignancy that, in the opinion of the investigator would preclude treatment with Sitagliptin and adequate follow up.
- History of acute pancreatitis within the last 5 years with the exception of gallstone pancreatitis.
- Positive test for anti-HIV.
- Active substance abuse, such as alcohol, inhaled or injection drugs within the previous one year.
- Pregnancy or inability to practice adequate contraception in women of childbearing potential.
- Evidence of hepatocellular carcinoma: alpha-fetoprotein levels greater than 200 ng/ml and/or liver mass on imaging study that is suggestive of liver cancer.
- Any other condition, which, in the opinion of the investigators would impede competence or compliance or possibility hinder completion of the study.
- Serum creatinine >1.5 mg/dl.
- Contraindications to Sitagliptin use :
- History of allergic reaction to Sitagliptin
- Patients with acute liver injury or unexplained persistent elevations in ALT > 500 U/L at baseline.
- Women who are pregnant or may become pregnant
- Nursing mothers
- Contraindications to MRI:
- The subject has any contraindication to MR imaging, such as patients with pacemakers, metallic cardiac valves, magnetic material such as surgical clips, implanted electronic infusion pumps or other conditions that would preclude proximity to a strong magnetic field.
- The subject has a history of extreme claustrophobia
- The subject cannot fit inside the MR scanner cavity
- 11. RECRUITMENT Enrollment of patients may be initiated once IRB approval is acquired and will continue until June 2015.
- Patients will be recruited from the following populations:
- Primary care and internal medicine clinics
- Tertiary referral clinics at the Hillcrest Campus and Perlman Clinics:
- GI/Liver clinic
- Liver transplant clinic
- Obesity clinic
- Bariatric surgery clinic
- Diabetes clinic
- Lipid disorders clinic
- Physicians taking care of the patients would provide information regarding the study and then either refer the patient to our clinic or ask the patient to directly contact the PI or research assistant.
- Patient would be given information regarding possible studies in NAFLD in liver clinic by their providers. We would ask the patient to call or email the PI or research assistant to further discuss the study, if they are interested.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Diego
San Diego, California, 92103
About this study
Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of diseases ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), the progressive form of liver disease that can lead to cirrhosis and liver-related mortality in persons who drink little or no alcohol. NAFLD is defined as the presence of hepatic steatosis with no evidence of hepatocellular injury in the form of ballooning of the hepatocytes. NASH is defined as the presence of hepatic steatosis and inflammation with hepatocyte injury (ballooning) with or without fibrosis. NASH is benign in many affected individuals but can cause progressive liver injury and, indeed, may be the major cause of cryptogenic cirrhosis1. Currently, there is no FDA approved treatment for NAFLD. Weight loss and exercise are the recommended but often difficult maintain these lifestyle changes in the long term and therefore therapeutic agents have been investigated. In this study, we propose to treat 50 patients with NAFLD and diabetes with either sitagliptin or placebo for 24 weeks. After an initial evaluation for insulin sensitivity and MRI liver fat distribution, patients will receive either 100 mg/day of sitagliptin or placebo. Patients will be monitored at regular intervals for symptoms of liver disease, side effects of sitagliptin and serum biochemical and metabolic indices. At the end of 24-weeks, patients will have a repeat medical evaluation, liver MRI and an optional liver biopsy. Pre and post treatment MRI-derived liver fat content and insulin sensitivity will be compared. The primary end point of successful therapy will be improvement in hepatic steatosis measured by MRI. Secondary end points will be improvement in insulin sensitivity and liver biochemistry.
Read the detailed description
Primary objectives:
- To examine the efficacy of sitagliptin 100 mg orally daily versus placebo in improving hepatic steatosis assessed by magnetic resonance imaging in patients with NAFLD.
Secondary objectives:
- To examine the efficacy of sitagliptin in improving serum AST in patients with NAFLD.
- To examine the efficacy of sitagliptin in improving serum ALT in patients with NAFLD.
- To examine the efficacy of sitagliptin in improving serum LDL in patients with NAFLD.
- To examine the efficacy of sitagliptin in the improvement of insulin sensitivity in patients with NAFLD.
- Conditions
- Non-alcoholic Fatty Liver Disease
- Being tested
- Sitagliptin, Placebo
- Medical subject headings
- Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SitagliptinDrug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
| Active drug | Experimental | Sitagliptin 100 mg Receives: Drug: Sitagliptin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage Change in Liver Fat Relative to Baseline Assessed by MRI-PDFF
Participants liver fat was measured at baseline and 24 weeks. This is the percentage change in liver fat assessed by MRI-PDFF and stratified by treatment group.
Measured: Baseline and 24 weeks
Secondary outcomes (4)
AST, Aspartate Aminotransferase
AST, measured in IU/L at baseline and 24 weeks
Measured: Baseline and 24 weeks
ALT, Alanine Aminotransferase
ALT, measured in IU/L at baseline and 24 weeks
Measured: Baseline and 24 weeks
LDL, Low-density Lipoprotein
LDL, measured in mg/dL at baseline and 24 weeks
Measured: Baseline and 24 weeks
HOMA-IR, Homeostatic Model Assessment of Insulin Resistance
HOMA-IR, calculated as [(glucose (mg/dL) X insulin (mg/dL)) / 405 ] at baseline and 24 weeks
Measured: Baseline and 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2013 (estimated)
- Study startJan 2014
- Primary completionJan 2016
- Study completionJan 2016
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 Non-alcoholic Fatty Liver DiseaseStudies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe sponsor's other registered studies.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rohit Loomba, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01963845
- Sponsor's protocol ID
- Sitagliptin-NAFLD
- Status last verified
- Oct 2016
- First submitted
- 11 Oct 2013
- Last updated
- 20 Oct 2016
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Nedrud MA, Chaudhry M, Middleton MS, Moylan CA, Lerebours R, Luo S, Farjat A, Guy C, Loomba R, Abdelmalek MF, Sirlin CB, Bashir MR. MRI Quantification of Placebo Effect in Nonalcoholic Steatohepatitis Clinical Trials. Radiology. 2023 Mar;306(3):e220743. doi: 10.1148/radiol.220743. Epub 2022 Nov 1.
PubMed 36318027
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sitagliptin Versus Placebo in the Treatment of Non-alcoholic Fatty Liver Disease
- ClinicalTrials.gov ID
- NCT01963845
- Acronym / sponsor ID
- Sitagliptin-NAFLD
- Conditions
- Non-alcoholic Fatty Liver Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Study start
- Jan 2014
- Primary completion
- Jan 2016 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 16 Oct 2013 (estimated)
- Results
- Posted 20 Oct 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of diseases ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), the progressive form of liver disease that can lead to cirrhosis and liver-related mortality in persons who drink little or no alcohol. NAFLD is defined as the presence of hepatic steatosis with no evidence of hepatocellular injury in the form of ballooning of the hepatocytes. NASH is defined as the presence of hepatic steatosis and inflammation with hepatocyte injury (ballooning) with or without fibrosis. NASH is benign in many affected individuals but can cause progressive liver injury and, indeed, may be the major cause of cryptogenic cirrhosis1. Currently, there is no FDA approved treatment for NAFLD. Weight loss and exercise are the recommended but often difficult maintain these lifestyle changes in the long term and therefore therapeutic agents have been investigated. In this study, we propose to treat 50 patients with NAFLD and diabetes with either sitagliptin or placebo for 24 weeks. After an initial evaluation for insulin sensitivity and MRI liver fat distribution, patients will receive either 100 mg/day of sitagliptin or placebo. Patients will be monitored at regular intervals for symptoms of liver disease, side effects of sitagliptin and serum biochemical and metabolic indices. At the end of 24-weeks, patients will have a repeat medical evaluation, liver MRI and an optional liver biopsy. Pre and post treatment MRI-derived liver fat content and insulin sensitivity will be compared. The primary end point of successful therapy will be improvement in hepatic steatosis measured by MRI. Secondary end points will be improvement in insulin sensitivity and liver biochemistry.
Detailed description
Primary objectives:
- To examine the efficacy of sitagliptin 100 mg orally daily versus placebo in improving hepatic steatosis assessed by magnetic resonance imaging in patients with NAFLD.
Secondary objectives:
- To examine the efficacy of sitagliptin in improving serum AST in patients with NAFLD.
- To examine the efficacy of sitagliptin in improving serum ALT in patients with NAFLD.
- To examine the efficacy of sitagliptin in improving serum LDL in patients with NAFLD.
- To examine the efficacy of sitagliptin in the improvement of insulin sensitivity in patients with NAFLD.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
| Active drug | Experimental | Drug: SitagliptinSitagliptin 100 mg |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age at entry at least 18 years.
- Serum alanine (ALT) or aspartate (AST) aminotransferase activities that are above the upper limits of normal. 19 or more in women and 30 or more in men.
- Evidence of hepatic steatosis or liver fat (≥5%) by MRI.
- Prediabetic patients and controlled diabetic patients as defined by the ADA position statement on diabetes mellitus. Prediabetics have a HbA1c of 5.7 to 6.4 and controlled diabetic patients have an HbA1c between 6.4 and 8.0.
- Written informed consent.
Key exclusion criteria (46 listed)
- Uncontrolled diabetes defined as a Hb A1c ≥ 8.0.
- Evidence of another form of liver disease.
- History of excess alcohol ingestion, averaging more than 30 gm/day (3 drinks per day) in the previous 10 years, or history of alcohol intake averaging greater than 10 gm/day (1 drink per day: 7 drinks per week) in the previous one year.
- Advanced liver disease: platelet counts < 75,000/mm3 or prothrombin time >16 seconds or history of bleeding disorders
- Decompensated liver disease, Child-Pugh score greater than or equal to 7 points
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 |
|---|---|---|
| Sitagliptin | Drug | Active drug |
| Placebo | Drug | Placebo |
Primary outcome
Percentage Change in Liver Fat Relative to Baseline Assessed by MRI-PDFF
Time frame: Baseline and 24 weeks
Participants liver fat was measured at baseline and 24 weeks. This is the percentage change in liver fat assessed by MRI-PDFF and stratified by treatment group.
4 secondary outcomes
AST, Aspartate Aminotransferase
Time frame: Baseline and 24 weeks
ALT, Alanine Aminotransferase
Time frame: Baseline and 24 weeks
LDL, Low-density Lipoprotein
Time frame: Baseline and 24 weeks
HOMA-IR, Homeostatic Model Assessment of Insulin Resistance
Time frame: Baseline and 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36318027Nedrud MA, Chaudhry M, Middleton MS, Moylan CA, Lerebours R, Luo S, Farjat A, Guy C, Loomba R, Abdelmalek MF, Sirlin CB, Bashir MR. MRI Quantification of Placebo Effect in Nonalcoholic Steatohepatitis Clinical Trials. Radiology. 2023 Mar;306(3):e220743. doi: 10.1148/radiol.220743. Epub 2022 Nov 1.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Sitagliptin in people with Non-alcoholic Fatty Liver Disease, run by University of California, San Diego 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 5 inclusion and 46 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 20 Oct 2016. 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. 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 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 20 Oct 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?
Percentage Change in Liver Fat Relative to Baseline Assessed by MRI-PDFF (time frame: Baseline and 24 weeks). 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 NCT01963845, 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 20 Oct 2016.