Condition category
Digestive System
Date applied
19/09/2005
Date assigned
27/10/2005
Last edited
11/10/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof Christopher Day

ORCID ID

Contact details

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

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

04/Q0904/47

Study information

Scientific title

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

Acronym

Study hypothesis

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

Not provided at time of registration

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

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

Phase

Not Applicable

Drug names

Orlistat

Primary outcome measures

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 trial start date

01/01/2005

Overall trial end date

31/12/2006

Reason abandoned

Eligibility

Participant 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)

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

50 patients will be recruited

Participant 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

Recruitment start date

01/01/2005

Recruitment end date

31/12/2006

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Medical School
Newcastle upon Tyne
NE2 4HH
United Kingdom

Sponsor information

Organisation

The Newcastle upon Tyne Hospitals NHS Trust (UK)

Sponsor details

Royal Victoria Infirmary
Queen Victoria Road
Newcastle upon Tyne
NE1 4LP
United Kingdom
+44 (0)191 282 5959
Craig.MacKerness@nuth.northy.nhs.uk

Sponsor type

Government

Website

Funders

Funder type

Industry

Funder name

Unrestricted educational grant from Roche Products Limited

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

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