Plain English Summary
Background and study aims:
Did you know that when people put on excess weight there is an increased danger of unseen liver injury? Fatty liver is up to five times more likely to occur in obese people than those who are a healthy weight. Fatty liver disease can exist without any symptoms, but it can also progress to serious liver damage. It has a range of disease states from non-threatening fat build-up (steatosis), to inflammatory steatohepatitis and fibrosis (cirrhosis). We know weight loss helps to reduce fatty liver, so disease progression can be reversed at this stage. However, once the disease reaches the fibrosis stage the liver damage is irreversible. Progression of the disease is thought to be affected by the body's resistance to its own insulin, coping strategies for excess fat, and automatic immune defences causing inflammation. These interactions are complex and we are not exactly sure what happens. We are investigating these interactions, to see what happens when an obese person follows a short-term very strict diet.
Who can participate?
Patients accepted for weight-loss surgery at Derby Hospitals NHS Foundation Trust.
What does the study involve?
Participants will follow a two-week diet of around 800 kcal/day either the standard hospital pre-operative diet or a meal replacement plan. Before the diet blood tests will be taken, as well as body weight. During the diet a food and drink diary will be completed. After the diet (at the time of the weight-loss surgery) - body weight will be measured, a further blood sample will be taken and biopsies of liver and fat
What are the possible benefits and risks of participating?
Overall, the study should help to identify the effects of the short-term diet on the liver, and wider effects on the body. It should also identify which type of diet is of most benefit to patients undergoing weight-loss surgery. As the participants follow the standard care pathway there are minimal additional risks. However, taking biopsies is an extra procedure and the surgeon will minimise any discomfort and manage any risks involved in this process.
Where is the study run from?
From the University of Nottingham with the co-operation of the regional Bariatric Surgical Service at Derby Hospitals NHS Foundation Trust.
When is the study starting and how long is it expected to run for?
Study recruitment started in May 2012 and will continue until June 2014, or until we have reached the target number of 100 participants, if sooner.
Who is funding the study?
Schools of Biomedical Sciences and Graduate Entry Medicine and Health, University of Nottingham.
Biotechnology and Biological Sciences Research Council (BBSRC).
Who is the main contact?
Prof. Ian Macdonald
ian.macdonald@nottingham.ac.uk
Trial website
Contact information
Type
Scientific
Primary contact
Prof Ian Macdonald
ORCID ID
Contact details
Professor of Metabolic Physiology
School of Biomedical Sciences
University of Nottingham Medical School
Queen's Medical Centre
Nottingham
NG7 2UH
United Kingdom
+44 (0)115 951 5151
ian.macdonald@nottingham.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
11770
Study information
Scientific title
Effects of short-term energy restriction on liver lipid content, metabolism and inflammatory status in severely obese adults
Acronym
EnR-Lin
Study hypothesis
A two week period of energy restriction will effect a reduction in liver lipid content, gene expression and plasma inflammatory markers, in severely obese individuals, relative to the level of energy restriction achieved.
Ethics approval
West Midlands - Coventry and Warwickshire, Health Research Authority, 25/01/2012, ref: 12/WM/0017
Study design
Randomised interventional trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Hepatology, Surgery
Intervention
Participants will be assigned randomly, to one of two intervention groups to undertake an energy restrictive diet for two weeks pre-operatively:
1. The Derby Hospitals standard pre-bariatric surgical diet
2. Meal replacement diet using nutritional supplements
Both diets will offer approximately 800kcal/d. No follow-up post-diet, participants reverted to the standard clinical care pathway.
Intervention type
Procedure/Surgery
Phase
Not Applicable
Drug names
Primary outcome measure
Fatty Liver Assessment is measured using histological assessment of tissue biopsy and NASH Clinical Research Network scoring system definitions at time of surgery (post-diet).
Secondary outcome measures
1. Body Weight Change is measured using a Marsden MPMS-300 high capacity weighing scale, before the diet, at the pre-op clinic, and after the diet, on the day of surgery
2. Diet Compliance is measured using a study-specific self-reported questionnaire with visual analogue scale on the day of surgery (post-diet)
Overall trial start date
01/10/2011
Overall trial end date
30/09/2014
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Patients accepted for weight loss surgery at Derby Hospitals NHS Foundation Trust
2. Male and female participants
3. Lower age limit = 18 years, no upper age limit
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
UK Sample Size: 100
Participant exclusion criteria
1. Secondary NAFLD
2. Diabetes mellitus treated by insulin, GLP1 or pioglitazone
3. Excess alcohol intake (exceeding national recommendations)
4. Patients receiving anti-inflammatory medication
5. Pregnancy and lactation
6. Any other condition judged by the investigative team to be clinically significant
Exclusions recommended by LighterLife (meal replacement plan):
7.1. Some cardiac conditions (including heart failure, arrhythmias, valve disease, requiring treatment)
7.2. Some cerebrovascular conditions. (Patients who have suffered cerebrovascular disease may participate if the following conditions are met; more than six months has passed and the patients condition is stable)
7.3. Schizophrenia, delusional and bipolar disorder, psychosis
7.4. Epilepsy or history of seizure
7.5. Kidney or liver disease (severe)
7.6. Total lactose intolerance
7.7. Type 1 diabetes
7.8. Anorexia or bulimia or other eating disorder undergoing or awaiting treatment.
7.9. Porphyria
7.10. Taking prescribed anticoagulants, digoxin, lithium or monoamine oxidase inhibitors (MAOIs)
7.11. Unstable angina
7.12. Major depressive disorder
Recruitment start date
08/05/2012
Recruitment end date
30/06/2014
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Royal Derby Hospital
Uttoxeter Road
Derby
DE22 3NE
United Kingdom
Sponsor information
Organisation
University of Nottingham (UK)
Sponsor details
Research Innovation Services
Kings Meadow Campus
Lenton Lane
Nottingham
NG7 2NR
United Kingdom
+44 (0)115 951 5151
ian.macdonald@nottingham.ac.uk
Sponsor type
University/education
Website
Funders
Funder type
Research council
Funder name
Biotechnology and Biological Sciences Research Council (UK)
Alternative name(s)
BBSRC
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Planned publication in a peer reviewed journal.
IPD Sharing plan:
The datasets generated and/or analysed during this study will be included in the subsequent results publication.
Intention to publish date
31/12/2017
Participant level data
Other
Basic results (scientific)
Publication list
2017 results in: https://www.ncbi.nlm.nih.gov/pubmed/28230324
Publication citations
Additional files
- ISRCTN65605485_PIS_08Jun12_V1.2.doc Uploaded 09/01/2017