A controlled trial of Orlistat (Xenical) for patients with non-alcoholic steatohepatitis (NASH)

ISRCTN	ISRCTN63745312
DOI	https://doi.org/10.1186/ISRCTN63745312
Secondary identifying numbers	04/Q0904/47

Submission date: 19/09/2005
Registration date: 27/10/2005
Last edited: 11/10/2016

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Digestive System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Christopher Day
Scientific

SCMS, Floor 4
William Leech Building
Medical School
Framlington Place
Newcastle upon Tyne
NE2 4HH
United Kingdom

Study information

Study design	Randomised controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Not specified
Study type	Treatment
Participant information sheet	Not available in web format, please use contact details to request a participant information sheet
Scientific title	A controlled trial of Orlistat (Xenical) for patients with non-alcoholic steatohepatitis (NASH)
Study objectives	The principal research objective is to determine if treatment with the drug Orlistat (product name Xenical), one tablet three times a day, along with a weight reducing diet and two multivitamin tablets a day, as compared to diet and multivitamins alone, is beneficial to the liver of overweight patients suffering from non-alcoholic steatohepatitis (NASH). The beneficial effect will be judged by performing a repeat liver biopsy to assess whether the degree of liver damage has improved since the biopsy on which the diagnosis of NASH was made.
Ethics approval(s)	Not provided at time of registration
Health condition(s) or problem(s) studied	Nonalcoholic steatohepatitis
Intervention	Orlistat (Xenical) one tablet (120 mg) three times a day for one year, along with a weight reducing diet and two multivitamin tablets a day versus diet and multivitamins alone.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Orlistat
Primary outcome measure	Overall necroinflammatory grade or fibrosis stage on repeat liver biopsy. A change of one point in grade or stage will be considered significant.
Secondary outcome measures	1. Liver biochemistry (alanine transaminase, aspartate transaminase, gamma, glutamyl transferase) 2. Insulin sensitivity assessed by HOMA index (derived from fasting glucose and insulin measurements) 3. Body mass index (BMI) 4. Quality of life assessed by the chronic liver disease questionnaire (CLDQ)
Overall study start date	01/01/2005
Completion date	31/12/2006

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	50 patients will be recruited
Key inclusion criteria	1. Adult more than 18 but less than 75 years Children will not be included in this study for three reasons: 1.1. The development of NASH in children may be due to different age-related metabolic processes than in adults 1.2. Children with NASH are always obese and their elevated aminotransferases normalise with weight loss or vitamin E treatment 1.3. The natural history of NASH in children is unknown and may not be sufficient to warrant the risk of using a new class of drug and performing a follow up liver biopsy. Orlistat is not approved for use in children 2. Body mass index (BMI) more than 28 kg/m^2. Orlistat is only licensed for patients with this degree of obesity 3. Liver biopsy obtained no more than six months before randomisation with a pathology report confirming that the histological diagnosis is consistent with NASH. A longer time period would increase the chances that the liver pathology had altered since the original biopsy 4. No more than 5% weight loss since liver biopsy. More weight loss would increase the chances that the liver pathology had altered since the original biopsy 5. Raised alanine transaminase (ALT) and/or aspartate transaminase (AST) and/or gamma-glutamyltransferase (GGT). This allows assessment of whether treatment improves liver blood tests 6. Ability to give informed consent 7. A satisfactory blood count, renal function and albumin. Ensures second biopsy likely to be safe (blood count, renal function) and that liver disease is not too far advanced (albumin)
Key exclusion criteria	1. Evidence of decompensated liver disease such as a history of or presence of ascites, bleeding varices, or spontaneous encephalopathy. These patients are considered too advanced to benefit from treatment 2. Any cause for chronic liver disease other than NASH 3. Alcohol consumption greater than sensible alcohol limits three units (~8-10 g) per day for males and two units per day for females during the past five years 4. Markers of active hepatitis virus infection (hepatitis B surface antigen [HBsAg], hepatitis C virus antibody [HCV Ab]) 5. Patients on medications known to be associated with NASH 6. Total parenteral nutrition (TPN) within the past six months 7. Prior obesity surgery including gastric or intestinal bypass procedures 8. Evidence of genetic haemochromatosis - patients with raised ferritin or transferrin and either homozygous for the C282Y HFE mutation or compound C282Y/H63D heterozygotes to be excluded. All these groups of patients are considered to have alternative causes for their liver disease or 'secondary' rather than true 'primary' NASH. 9. Type one diabetes or type two diabetes mellitus on any form of treatment (either insulin or oral hypoglycaemic) 10. Previous therapy for NASH including ursodeoxycholic acid, metformin, glitazones 11. Current treatment with fibrates. These treatments may be of benefit in NASH and would therefore confound any effects of Orlistat 12. History of prior organ transplantation. Immunosuppression and risk of recurrent disease (in liver transplant recipients) likely to confound any effects of Orlistat
Date of first enrolment	01/01/2005
Date of final enrolment	31/12/2006

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Medical School

Newcastle upon Tyne
NE2 4HH
United Kingdom

Sponsor information

The Newcastle upon Tyne Hospitals NHS Trust (UK)
Hospital/treatment centre

Royal Victoria Infirmary
Queen Victoria Road
Newcastle upon Tyne
NE1 4LP
England
United Kingdom

Phone	+44 (0)191 282 5959
Email	Craig.MacKerness@nuth.northy.nhs.uk
"ROR"	https://ror.org/05p40t847

Funders

Funder type

Industry

Unrestricted educational grant from Roche Products Limited

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Editorial Notes

11/10/2016: No publications found, verifying study status with principal investigator.