NCT02654665

Brief 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. 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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
36

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Mar 2014

Longer than P75 for phase_3

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2014

Completed
1.9 years until next milestone

First Submitted

Initial submission to the registry

January 11, 2016

Completed
2 days until next milestone

First Posted

Study publicly available on registry

January 13, 2016

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2017

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2018

Completed
Last Updated

January 30, 2018

Status Verified

January 1, 2018

Enrollment Period

3.8 years

First QC Date

January 11, 2016

Last Update Submit

January 26, 2018

Conditions

Non-alcoholic Fatty Liver Disease (NAFLD)Weight LossNon-alcoholic Steatohepatitis (NASH)

Outcome Measures

Primary Outcomes (1)

  • Improvement in NASH

    Reduction/normalization in transaminases, liver fat

    12 months

Study Arms (3)

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.

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.

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.

Drug: Liraglutide

Interventions

Lifestyle modificationBEHAVIORAL

Diet and exercise designed for 5-7% weight loss over 6 months

Liraglutide
LiraglutideDRUG

GLP-1 agonist

Also known as: Victoza
Bariatric SurgeryDiet modification and exercise

Eligibility Criteria

Age21 Years - 65 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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
  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Changi General Hospital

Singapore, 529889, Singapore

RECRUITING

Related Publications (1)

  • 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.

    PMID: 30721572DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver DiseaseWeight Loss

Interventions

Liraglutide

Condition Hierarchy (Ancestors)

Fatty LiverLiver DiseasesDigestive System DiseasesBody Weight ChangesBody WeightSigns and SymptomsPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1Glucagon-Like PeptidesProglucagonGastrointestinal HormonesHormonesHormones, Hormone Substitutes, and Hormone Antagonists

Central Study Contacts

Ai-Wyn Tan

CONTACT

+6568501924

Study Design

Study Type
interventional
Phase
phase 3
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Chief & Senior Consultant

Study Record Dates

First Submitted

January 11, 2016

First Posted

January 13, 2016

Study Start

March 1, 2014

Primary Completion

December 1, 2017

Study Completion

December 1, 2018

Last Updated

January 30, 2018

Record last verified: 2018-01

Data Sharing

IPD Sharing
Will share

Locations

SG(1)