Brain imaging responses to food images and food in insulin resistance - intervention

ISRCTN	ISRCTN51099878
DOI	https://doi.org/10.1186/ISRCTN51099878
Secondary identifying numbers	9117

Submission date: 14/12/2010
Registration date: 14/12/2010
Last edited: 29/03/2018

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nutritional, Metabolic, Endocrine

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
Obesity (being very overweight) and health problems related to obesity (including type 2 diabetes) are becoming more common, causing long-term ill health. As yet we do not understand why some people are particularly prone to weight gain and diabetes. One possibility is that people who are more prone to obesity and diabetes have a malfunction in the brain mechanisms that stop their desire to eat more after a meal. Gaining further knowledge of the way the brain controls eating will help the development of new ways to prevent and treat these diseases. This study looks at the way the brain controls appetite by using functional magnetic resonance imaging (fMRI), comparing the results from people who are “insulin resistant” and therefore at a higher risk of developing diabetes with people who are “insulin sensitive” and therefore at a lower risk of developing diabetes.

Who can participate?
Men aged between 18-65 years with a body mass index (BMI) of no more than 30 kg/m2. Insulin sensitive participants should not have any family history of diabetes mellitus. Insulin resistant subjects must have first degree relatives (i.e. parent, sibling or child) with type 2 diabetes.

What does the study involve?
All participants that have been checked to see if they can take part ( see http://www.isrctn.com/ISRCTN18732138) have a series of functional resonance brain imaging (fMRI) studies to see how insulin resistance effects the response of the brain to food. These studies are completed within four weeks. The insulin resistant volunteers are then randomly allocated to one of two groups. Those in group 1 receive insulin sensitisation therapy for three months. Those in group 2 are given a placebo for three months. These volunteers then do the same fMRI studies that they did at the beginning of the study.

What are the possible benefits and risks of participating?
Not provided at time of registration

Where is the study run from?
King's College Hospital NHS Trust

When is the study starting and how long is it expected to run for?
December 2010 to November 2013

Who is funding the study?
Diabetes UK

Who is the main contact?
Professor Stephanie Amiel
stephanie.amiel@kcl.ac.uk

Contact information

Prof Stephanie Amiel
Scientific

King's College Hospital NHS Trust
Bessemer Road
London
SE5 9PJ
United Kingdom

Phone	+44 (0) 20 3299 4161
Email	stephanie.amiel@kcl.ac.uk

Study information

Study design	Single centre randomised observational treatment based case-control study
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title	Brain imaging responses to food images and food in insulin resistance: a single centre randomised observational treatment based case-control study
Study acronym	DRN 518
Study objectives	Obesity and related health problems including type 2 diabetes are becoming more common, causing long-term ill health. As yet, it is not understood why some people are particularly prone to weight gain and diabetes. One possibility is a malfunction in the brain mechanisms that stop our desire to eat more after a meal in people predisposed to obesity and diabetes. Gaining further knowledge of the way the brain controls eating will help the development of new ways to prevent and treat these diseases. The project will look at the way the brain controls appetite by using functional magnetic resonance imaging (fMRI). This is a method of taking images of the brain that will allow us to see the activity of brain regions that control eating. Brain responses will be studied after eating in healthy relatives of people with diabetes, who are "insulin resistant", where the body is less responsive to insulin, a hormone normally produced by the body to control sugar (glucose) levels. These people will therefore be at higher risk of developing diabetes and obesity. They will be compared to people who are insulin sensitive, at lower risk of diabetes. The impact of treating insulin resistance on these brain responses will then be investigated. This will allow researchers to see if the brain controls eating differently in those at risk of diabetes and obesity, and whether it can be reversed. The imaging methods that are developed may also permit the early assessment of potential therapies to improve appetite control, aiding the development of new ways to prevent or treat obesity and diabetes in the future.
Ethics approval(s)	South East London REC3 (formally King's College Hospital REC), 18/06/2010, ref: 10/H0808/47b
Health condition(s) or problem(s) studied	Topic: Diabetes Research Network; Subtopic: Type 2; Disease: Obesity
Intervention	Both insulin sensitive and insulin resistant volunteers identified as meeting the inclusion criteria during the initial screening study (UKCRN 9515, DRN 546, ISRCTN18732138), will undergo a series of functional magnetic resonance brain imaging (fMRI) studies, to investigate the effect of insulin resistance on brain responses to food ingestion and food cues. These initial fMRI studies will be completed within a four week period. To determine whether the effect of insulin resistance on these central responses is reversible, the insulin resistant volunteers will then be randomised to receive either placebo or insulin sensitisation therapy during a 3 month intervention period, before the fMRI studies are repeated.
Intervention type	Other
Primary outcome measure	Brain responses to food measured by using functional magnetic resonance imaging
Secondary outcome measures	Insulin sensitivity, measured at each functional magnetic resonance imaging scan visit
Overall study start date	01/12/2010
Completion date	01/11/2013

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Male
Target number of participants	Planned sample size: 48; UK sample size: 48
Key inclusion criteria	All subjects (insulin sensitive and insulin resistant): 1. Men 2. Age 18 - 65 years (inclusive at time of recruitment) 3. Right-handed 4. English speaking 5. No active medical illness including diabetes mellitus 6. Body mass index (BMI) less than or equal to 30 kg/m2 Insulin sensitive subjects: 7. No family history of diabetes mellitus 8. Insulin sensitive (determined by homeostatic model assessment - insulin resistance [HOMA2-IR] less than 1.47) Insulin resistant subjects: 9. First degree relatives of patients with type 2 diabetes mellitus 10. Insulin resistance (determined by HOMA2-IR) greater than or equal to 1.47
Key exclusion criteria	1. Women 2. Left handedness 3. Current or past history of significant substance abuse or eating disorders 4. Use of medication that may affect brain activity (e.g. antidepressants, anticonvulsants, antipsychotic drugs), drugs for obesity (orlistat or sibutramine) or drugs that lower glucose (e.g. metformin, sulphonylureas, thiazolidinediones, incretins or insulin) 5. Inability to understand spoken and/or written English 6. Claustrophobia (because of the small bore of the MR scanner) 7. BMI greater than 30 kg/m2 8. Cortraindication to MRI (pacemaker in situ, extensive dental work, history of penetrating eye trauma, precense of surgical metal clips etc.) 9. Presence of diabetes
Date of first enrolment	01/12/2010
Date of final enrolment	01/11/2013

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

King's College Hospital NHS Trust

London
SE5 9PJ
United Kingdom

Sponsor information

Kings College London (KCL)
University/education

Hodgkin Building
New Hunts House
Guy's Campus
London
SE1 1UL
England
United Kingdom

Website	http://www.kcl.ac.uk/index.aspx

King's College Hospital NHS Foundation Trust
Hospital/treatment centre

Denmark Hill
London
SE5 9RS
England
United Kingdom

King's College London
Not defined

Website	http://www.kcl.ac.uk/index.aspx
"ROR"	https://ror.org/0220mzb33

Funders

Funder type

Charity

Diabetes UK
Private sector organisation / Trusts, charities, foundations (both public and private)

Alternative name(s): DIABETES UK LIMITED, British Diabetic Association
Location: United Kingdom

Kings College London
Government organisation / Universities (academic only)

Alternative name(s): King's College, King's College London UK, KCL, King's
Location: United Kingdom

National Institute for Health Research
Government organisation / National government

Alternative name(s): National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
Location: United Kingdom

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	29/03/2018: Results presented at European Association for the Study of Diabetes Annual Meeting 2013 (https://www.easd.org/virtualmeeting/home.html#!resources/increasing-homa-ir-modulates-brain-responses-to-meal-ingestion-in-insulin-sensitive-men-a-continuous-arterial-spin-labelling-functional-magnetic-resonance-imaging-study)
IPD sharing plan

Editorial Notes

29/03/2018: Conference proceedings added to publication and dissemination plan.
08/02/2016: No publications found, verifying study status with principal investigator