Non-alcoholic Fatty Liver Disease (NAFLD)Phase 3CGH-LiNASHNCT02654665
Comparing Effects of Liraglutide and Bariatric Surgery on Weight Loss, Liver Function, Body Composition, Insulin Resistance, Endothelial Function and Biomarkers of Non-alcoholic Steatohepatitis (NASH) in Obese Asian Adults
A Phase 3 study testing Lifestyle modification and Liraglutide in people with Non-alcoholic Fatty Liver Disease (NAFLD) and Weight Loss, run by Changi General Hospital at 1 site in Singapore.
Trial summary
Non-alcoholic fatty liver disease (NAFLD) is defined by presence of hepatic steatosis (fat accumulation in liver cells), either by imaging or by biopsy and absence of causes for secondary hepatic fat accumulation such as significant alcohol consumption, medications, or hereditary disorders. Read more about this study
- Who is it for?
- Ages 21 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Non-alcoholic Fatty Liver Disease (NAFLD), Weight Loss, Non-alcoholic Steatohepatitis (NASH)
- What is being tested?
- Lifestyle modification and Liraglutide
- Type of treatment
- Injection or infusion, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteSingapore
- Study dates
- Mar 2014to Dec 2018
- Phase
- Phase 3
- 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 21 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Body mass index > 27.5 kg/m2
- Waist circumference (WC) > 90 cm (male) or > 80 cm (female)
- Diagnosis of NASH based on Liver Function Test Results ,Ultrasound Hepato-Biliary System (HBS) findings and / or Liver Biopsy
- HbA1c < 8%* *Subjects in the bariatric surgery arm will not need to fulfil this criterion.
Who cannot join
- Currently using insulin-sensitising agents (metformin, pioglitazone), weight loss medication (orlistat, phentermine). Patients taking any of these drugs will require a three month washout period before enrolment.
- Pregnancy
- Significant cardiovascular or respiratory disease
- Renal impairment with eGFR < 60 ml/min
- Hepatitis B or C carrier, liver disease other than NAFLD
- History of pancreatitis
Show all 12Show fewer
- Personal or family history of multiple endocrine neoplasia type 2 or thyroid carcinoma
- Untreated hypothyroidism or hyperthyroidism
- Current psychiatric illness
- Cardiac pacemaker, metallic prosthetic heart valves and other contraindications to MRI scan
- Current smoker
- Alcohol intake ≥ 14 units/week
Trial locations and contacts
1 site in 1 country.
Ai-Wyn Tan contact
Singapore1 site, 1 recruiting
- Recruiting
Changi General Hospital
Singapore, 529889
Joan Khoo, MRCP, +658503807
About this study
Non-alcoholic fatty liver disease (NAFLD) is defined by presence of hepatic steatosis (fat accumulation in liver cells), either by imaging or by biopsy and absence of causes for secondary hepatic fat accumulation such as significant alcohol consumption, medications, or hereditary disorders. In the majority of patients, NAFLD is associated with risk factors for cardiovascular disease such as obesity, diabetes mellitus, and high cholesterol, and may lead to irreversible liver damage. Non-alcoholic steatohepatitis (NASH) is a more severe form of NAFLD and is present in up to 30% of obese adults. NASH is defined by hepatic steatosis and inflammation with hepatocyte injury with or without fibrosis (hardening of the liver).
The prevalence, morbidity and mortality of NAFLD is increasing, particularly in the Asia-Pacific region where there will be an estimated 300 million obese people by 2030. Weight loss is the first-line treatment for NAFLD in obese individuals, but the utility of lifestyle modification with diet and exercise is limited by difficulties in sustaining compliance and by eventual weight regain. Bariatric (weight loss) surgery produces the greatest amount of weight loss but is limited by cost, patient acceptance, and complications. The efficacy of drugs for NASH, such as vitamin E and medication to lower cholesterol and glucose, remains unclear. Liraglutide, a glucagon-like peptide (GLP-1) analogue, is an injectable medication which has been shown to induce weight loss and lower glucose in obese adults. There is little information on the effects of GLP-1 analogues on NASH, particularly in comparison to other modalities of weight loss such as surgery. This study aims to compare the efficacy and safety of lifestyle modification, liraglutide and surgery, for weight loss in conjunction with reducing severity of NASH, and for insulin resistance, high cholesterol and other cardiovascular risk factors.
Read the detailed description
The morbidity and mortality from non-alcoholic fatty liver disease (NAFLD), the most common liver disease worldwide, are rapidly increasing as a result of the global explosion in obesity, particularly in the Asia-Pacific region where there will be an estimated 300 million obese people by 20302. Non-alcoholic steatohepatitis (NASH), a subset of NAFLD, which is present in up to 30% of obese adults, leads to irreversible liver cirrhosis, and is associated with type 2 diabetes, cardiovascular disease and increased morbidity and mortality. Weight loss has established efficacy on NASH-associated cardiometabolic abnormalities and disease activity and severity. Diet and exercise produce a modest effect on NASH which is limited by weight regain, even with intensive lifestyle modification. Bariatric surgery produces the greatest amount of weight loss, but is less acceptable to many patients than lifestyle modification or medical therapy, and is limited by cost and complications, particularly post-surgical malabsorption and potential psychological complications. The efficacy of previously-studied medications on NASH, such as statins, insulin sensitizers and ursodeoxycholic acid, remains unclear.
This study therefore aims to compare the efficacy and safety of a medication which induces weight loss and reduces insulin resistance, with that of lifestyle modification (diet and exercise), and bariatric surgery, for improvement in NASH severity, insulin resistance and other markers of cardiovascular risk. Liraglutide is an injectable glucagon-like peptide-1 (GLP-1) analogue which is indicated for treatment of type 2 diabetes in adults. It has been shown to induce weight loss and reduction in insulin resistance in type 2 diabetic and obese patients. Treatment with clinically relevant doses of liraglutide for at least 20 weeks leads to weight loss in obese patients with or without type 2 diabetes. However, there is little information on the effects of GLP-1 analogues on NASH, particularly in comparison to other modalities of weight loss such as surgery.
Our study will also compare the accuracy of magnetic resonance imaging (MRI), the current noninvasive reference standard method for measuring hepatic fat content, with liver biopsy for staging of NASH. Biopsy is the current gold standard, but carries higher procedural risks, and is less convenient and acceptable to patients than non-invasive methods of evaluating severity and activity of NASH. Hence liver biopsy for week 0, 26 and week 52 is optional based on patient consent. We will also measure biomarkers for altered hepatic lipid partitioning and adipokine action, increased oxidative stress and free fatty acid lipotoxicity, which have been implicated in the pathogenesis of NAFLD, and which may be useful non-invasive methods for evaluating the severity of NASH and the efficacy of treatment.
- Conditions
- Non-alcoholic Fatty Liver Disease (NAFLD), Weight Loss, Non-alcoholic Steatohepatitis (NASH)
- Being tested
- Lifestyle modification, Liraglutide
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Weight Loss
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lifestyle modificationBehavioural
Diet and exercise designed for 5-7% weight loss over 6 months
LiraglutideDrug
Also called Victoza
GLP-1 agonist
| Study group | Role | What they receive |
|---|---|---|
| Liraglutide | Experimental | Liraglutide will be administered once daily by subcutaneous injection at a starting dose of 0.6 mg, increasing at 0.6 mg/week increments to a maximum of 3.0 mg over the next 6 weeks, as tolerated. Receives: Behavioral: Lifestyle modification |
| Bariatric Surgery | Active comparator | Subjects will have outcomes measured within 28 days before surgery. Post-operative management and frequency of follow-up visits will be decided by the bariatric surgeon. Study visits for biochemical and endothelial function testing; MRI and liver biopsy and / or fibroscan will follow the same schedule as that of the lifestyle and liraglutide arms. Target weight loss for the first 26 weeks post-surgery is at least 30% of excess body weight. Receives: Drug: Liraglutide |
| Diet modification and exercise | Active comparator | Exercise will be used to induce and maintain weight loss in a 26-week Weight Management Program. Each subject will follow an aerobic exercise prescription of moderate intensity (60-75% maximum heart rate) to expend 2000-3000 kcal/week, lasting 30-60 minutes each session (over 5-7 sessions). Subjects will be instructed by sports trainers, compliance reviewed and adjusted if necessary to maintain the targeted total energy expenditure to produce weight loss of at least 7% over 26 weeks. Receives: Drug: Liraglutide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvement in NASH
Reduction/normalization in transaminases, liver fat
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2016 (estimated)
- Study startMar 2014
- Primary completionDec 2017
- Study completionDec 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non-alcoholic Fatty Liver Disease (NAFLD)Studies 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 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Changi General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Joan Khoo Joo Ching, Changi General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02654665
- Sponsor's protocol ID
- CGH-LiNASH
- Acronym
- CGH-LiNASH
- Status last verified
- Jan 2018
- First submitted
- 11 Jan 2016
- Last updated
- 30 Jan 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes
Publications
Khoo J, Hsiang JC, Taneja R, Koo SH, Soon GH, Kam CJ, Law NM, Ang TL. Randomized trial comparing effects of weight loss by liraglutide with lifestyle modification in non-alcoholic fatty liver disease. Liver Int. 2019 May;39(5):941-949. doi: 10.1111/liv.14065. Epub 2019 Feb 24.
PubMed 30721572
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparing Effects of Liraglutide and Bariatric Surgery on Weight Loss, Liver Function, Body Composition, Insulin Resistance, Endothelial Function and Biomarkers of Non-alcoholic Steatohepatitis (NASH) in Obese Asian Adults
- ClinicalTrials.gov ID
- NCT02654665
- Acronym / sponsor ID
- CGH-LiNASH / CGH-LiNASH
- Conditions
- Non-alcoholic Fatty Liver Disease (NAFLD), Weight Loss, Non-alcoholic Steatohepatitis (NASH)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Changi General HospitalUniversity, hospital or other
- Study start
- Mar 2014
- Primary completion
- Dec 2017 (actual)
- Study completion
- Dec 2018 (estimated)
- First posted
- 13 Jan 2016 (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.
Non-alcoholic fatty liver disease (NAFLD) is defined by presence of hepatic steatosis (fat accumulation in liver cells), either by imaging or by biopsy and absence of causes for secondary hepatic fat accumulation such as significant alcohol consumption, medications, or hereditary disorders. In the majority of patients, NAFLD is associated with risk factors for cardiovascular disease such as obesity, diabetes mellitus, and high cholesterol, and may lead to irreversible liver damage. Non-alcoholic steatohepatitis (NASH) is a more severe form of NAFLD and is present in up to 30% of obese adults. NASH is defined by hepatic steatosis and inflammation with hepatocyte injury with or without fibrosis (hardening of the liver).
The prevalence, morbidity and mortality of NAFLD is increasing, particularly in the Asia-Pacific region where there will be an estimated 300 million obese people by 2030. Weight loss is the first-line treatment for NAFLD in obese individuals, but the utility of lifestyle modification with diet and exercise is limited by difficulties in sustaining compliance and by eventual weight regain. Bariatric (weight loss) surgery produces the greatest amount of weight loss but is limited by cost, patient acceptance, and complications. The efficacy of drugs for NASH, such as vitamin E and medication to lower cholesterol and glucose, remains unclear. Liraglutide, a glucagon-like peptide (GLP-1) analogue, is an injectable medication which has been shown to induce weight loss and lower glucose in obese adults. There is little information on the effects of GLP-1 analogues on NASH, particularly in comparison to other modalities of weight loss such as surgery. This study aims to compare the efficacy and safety of lifestyle modification, liraglutide and surgery, for weight loss in conjunction with reducing severity of NASH, and for insulin resistance, high cholesterol and other cardiovascular risk factors.
Detailed description
The morbidity and mortality from non-alcoholic fatty liver disease (NAFLD), the most common liver disease worldwide, are rapidly increasing as a result of the global explosion in obesity, particularly in the Asia-Pacific region where there will be an estimated 300 million obese people by 20302. Non-alcoholic steatohepatitis (NASH), a subset of NAFLD, which is present in up to 30% of obese adults, leads to irreversible liver cirrhosis, and is associated with type 2 diabetes, cardiovascular disease and increased morbidity and mortality. Weight loss has established efficacy on NASH-associated cardiometabolic abnormalities and disease activity and severity. Diet and exercise produce a modest effect on NASH which is limited by weight regain, even with intensive lifestyle modification. Bariatric surgery produces the greatest amount of weight loss, but is less acceptable to many patients than lifestyle modification or medical therapy, and is limited by cost and complications, particularly post-surgical malabsorption and potential psychological complications. The efficacy of previously-studied medications on NASH, such as statins, insulin sensitizers and ursodeoxycholic acid, remains unclear.
This study therefore aims to compare the efficacy and safety of a medication which induces weight loss and reduces insulin resistance, with that of lifestyle modification (diet and exercise), and bariatric surgery, for improvement in NASH severity, insulin resistance and other markers of cardiovascular risk. Liraglutide is an injectable glucagon-like peptide-1 (GLP-1) analogue which is indicated for treatment of type 2 diabetes in adults. It has been shown to induce weight loss and reduction in insulin resistance in type 2 diabetic and obese patients. Treatment with clinically relevant doses of liraglutide for at least 20 weeks leads to weight loss in obese patients with or without type 2 diabetes. However, there is little information on the effects of GLP-1 analogues on NASH, particularly in comparison to other modalities of weight loss such as surgery.
Our study will also compare the accuracy of magnetic resonance imaging (MRI), the current noninvasive reference standard method for measuring hepatic fat content, with liver biopsy for staging of NASH. Biopsy is the current gold standard, but carries higher procedural risks, and is less convenient and acceptable to patients than non-invasive methods of evaluating severity and activity of NASH. Hence liver biopsy for week 0, 26 and week 52 is optional based on patient consent. We will also measure biomarkers for altered hepatic lipid partitioning and adipokine action, increased oxidative stress and free fatty acid lipotoxicity, which have been implicated in the pathogenesis of NAFLD, and which may be useful non-invasive methods for evaluating the severity of NASH and the efficacy of treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Liraglutide | Experimental | Behavioral: Lifestyle modificationLiraglutide will be administered once daily by subcutaneous injection at a starting dose of 0.6 mg, increasing at 0.6 mg/week increments to a maximum of 3.0 mg over the next 6 weeks, as tolerated. |
| Bariatric Surgery | Active comparator | Drug: LiraglutideSubjects will have outcomes measured within 28 days before surgery. Post-operative management and frequency of follow-up visits will be decided by the bariatric surgeon. Study visits for biochemical and endothelial function testing; MRI and liver biopsy and / or fibroscan will follow the same schedule as that of the lifestyle and liraglutide arms. Target weight loss for the first 26 weeks post-surgery is at least 30% of excess body weight. |
| Diet modification and exercise | Active comparator | Drug: LiraglutideExercise will be used to induce and maintain weight loss in a 26-week Weight Management Program. Each subject will follow an aerobic exercise prescription of moderate intensity (60-75% maximum heart rate) to expend 2000-3000 kcal/week, lasting 30-60 minutes each session (over 5-7 sessions). Subjects will be instructed by sports trainers, compliance reviewed and adjusted if necessary to maintain the targeted total energy expenditure to produce weight loss of at least 7% over 26 weeks. |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Body mass index > 27.5 kg/m2
- Waist circumference (WC) > 90 cm (male) or > 80 cm (female)
- Diagnosis of NASH based on Liver Function Test Results ,Ultrasound Hepato-Biliary System (HBS) findings and / or Liver Biopsy
- HbA1c < 8%* *Subjects in the bariatric surgery arm will not need to fulfil this criterion.
Key exclusion criteria (12 listed)
- Currently using insulin-sensitising agents (metformin, pioglitazone), weight loss medication (orlistat, phentermine). Patients taking any of these drugs will require a three month washout period before enrolment.
- Pregnancy
- Significant cardiovascular or respiratory disease
- Renal impairment with eGFR < 60 ml/min
- Hepatitis B or C carrier, liver disease other than NAFLD
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 |
|---|---|---|
| Lifestyle modificationDiet and exercise designed for 5-7% weight loss over 6 months | Behavioural | Liraglutide |
| LiraglutideAlso: VictozaGLP-1 agonist | Drug | Bariatric Surgery, Diet modification and exercise |
Primary outcome
Improvement in NASH
Time frame: 12 months
Reduction/normalization in transaminases, liver fat
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2018.
- Derived from this study: PubMed 30721572Khoo J, Hsiang JC, Taneja R, Koo SH, Soon GH, Kam CJ, Law NM, Ang TL. Randomized trial comparing effects of weight loss by liraglutide with lifestyle modification in non-alcoholic fatty liver disease. Liver Int. 2019 May;39(5):941-949. doi: 10.1111/liv.14065. Epub 2019 Feb 24.
- Individual participant dataSharing planned: Yes
Related trials for Non-alcoholic Fatty Liver Disease (NAFLD)
Not yet recruiting
Efficacy of Carnitine Complex in Improving Hepatic Steatosis in Potential Liver Donors
Hepatic Steatosis, Fatty Liver
Recruiting
NAFLD Clinical Care Pathway
NAFLD, MASLD
RecruitingPhase 3
Trial to Evaluate ALN-CIDEB in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Metabolic Dysfunction-Associated Steatotic Liver Disease, MASLD
RecruitingPhase 1
A Study of Efimosfermin Alfa in Adults With Hepatic Impairment
Non-alcoholic Fatty Liver Disease
RecruitingPhase 2
A Study of Efimosfermin Alfa in Participants With Biopsy-confirmed Cirrhosis (Compensated) Due to MASH
Metabolic Dysfunction-Associated Steatohepatitis, Non-alcoholic Fatty Liver Disease
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.
Ai-Wyn Tan contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Lifestyle modification and Liraglutide in people with Non-alcoholic Fatty Liver Disease (NAFLD) and Weight Loss, run by Changi General Hospital at 1 site in Singapore.
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 4 inclusion and 12 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: status not confirmed, as of the sponsor's last update on 30 Jan 2018. 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 Singapore. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ai-Wyn Tan (+6568501924), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Improvement in NASH (time frame: 12 months). 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 NCT02654665, 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 30 Jan 2018.