Investigation of the cerebral responses to hunger, satiety and food ingestion in people with obesity-related insulin resistance and Type 2 diabetes. A neuroimaging study using an obesity surgery (Roux-en-Y Gastric Bypass) model

ISRCTN	ISRCTN02683156
DOI	https://doi.org/10.1186/ISRCTN02683156
Secondary identifying numbers	7405

Submission date: 30/06/2010
Registration date: 30/06/2010
Last edited: 11/04/2017

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

Not provided at time of registration

Contact information

Dr Katharine Hunt
Scientific

133 Coldharbour Lane
London
SE5 9NU
United Kingdom

Email	katharine.f.hunt@kcl.ac.uk

Study information

Study design	Single-centre observational screening cross-sectional study
Primary study design	Observational
Secondary study design	Cross sectional study
Study setting(s)	Hospital
Study type	Screening
Participant information sheet	Not available in web format, please use the contact details to request a patient information sheet
Scientific title	Investigation of the cerebral responses to hunger, satiety and food ingestion in people with obesity-related insulin resistance and Type 2 diabetes. A neuroimaging study using an obesity surgery (Roux-en-Y Gastric Bypass) model
Study acronym	DRN 381 (RYGB)
Study objectives	Obesity and related health problems such as Type 2 diabetes are becoming much more common and cause ill health and early death. We do not understand why some people are particularly prone to weight gain and diabetes. One possible explanation is that brain mechanisms controlling food intake are abnormal in people predisposed to obesity and/or diabetes. Roux-en-Y Gastric Bypass (RYGB), a type of surgery for obesity, is effective at causing weight loss. People who have had RYGB exhibit changes in appetite (the drive to eat) and/or satiation (feeling of fullness). Hypotheses: Our overarching hypothesis is that brain control of food intake is abnormal in insulin-resistant states, predisposing to obesity and Type 2 diabetes, in a way that is amenable to correction e.g. by RYGB and to increase our understanding of the mechanisms involved. We will examine the following hypotheses: 1. That in people who have had successful RYGB the central (brain) responses to food ingestion are different when the effect of surgery is inhibited (mimicking the pre-operative state) and when it is active (the post-operative state) 2. That the central responses to food ingestion are abnormal in insulin resistance and obesity Protocol: We are measuring, in the fasted and fed (post 400 kcal meal) state: regional brain activation using (18F)-fluoro-deoxyglucose positron emission tomography (FDG-PET) brain imaging; gut peptides; and appetite and satiety (using visual analogue scales and an ad-libitum meal). Study One will be performed in 12 people who have lost weight after RYGB in their normal state and using somatostatin infusion to inhibit the satiety effects of surgery. Study Two compares responses between three groups of 12 people (who have not had obesity surgery): 1. Normal weight (body mass index [BMI] 20 - 25 kg/m^2) 2. Overweight insulin sensitive (BMI 25 - 40 kg/m^2 and updated homeostatic model assessment [HOMA2-IR] greater than or equal to 0.76) 3. Overweight insulin resistant (BMI 25 - 40 kg/m2 and HOMA2-IR greater than or equal to 1.47)
Ethics approval(s)	MREC approved, ref: 08/H0801/152
Health condition(s) or problem(s) studied	Topic: Diabetes Research Network; Subtopic: Type 2; Disease: Obesity
Intervention	Intravenous somatostatin infusion (to inhibit the satiety effects of RYGB) compared to intravenous saline control (Study One, post RYGB only). Post 400 kcal meal compared to no food intake.
Intervention type	Other
Primary outcome measure	Regional brain activation: regional brain activation using FDG-PET brain imaging
Secondary outcome measures	1. Appetite and satiety using visaul analogue scales and an ad-libitum meal 2. Gut peptides
Overall study start date	03/06/2009
Completion date	30/09/2011

Eligibility

Participant type(s)	Mixed
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	Planned sample size: 48; UK sample size: 48
Key inclusion criteria	1. Aged 18 years or over 2. Able to provide informed consent to participate in the study 3. Able to lie flat in the scanner for duration of scans 4. Right handedness (because of the possibility of lateralisation of cerebral responses) 5. For women of childbearing potential in all groups: 5.1. Using effective form of contraception 5.2. Willing to have a pregnancy test at the start of each scanning visit 5.3. Willing to attend for scanning visits during the first 10 days of their menstrual cycle 6. For STUDY ONE (RYGB): 6.1. Roux-en-Y gastric bypass 3 months to 10 years previously 6.2. BMI 25 - 40 kg/m^2 6.3. Weight loss of more than 10% of excess body weight since surgery 7. For STUDY TWO, Group A (non-overweight, no obesity surgery group): 7.1. No previous obesity surgery 7.2. BMI 20 - 25 kg/m^2 8. For STUDY TWO, Group B (overweight/obese, no obesity surgery with insulin resistance with or without Type 2 diabetes): 8.1. No previous obesity surgery 8.2. BMI 25 - 40 kg/m^2 8.3. HOMA2-IR greater than or equal to 1.47 with or without Type 2 diabetes (managed with diet/exercise/metformin only) 9. For STUDY TWO, Group C (overweight/obese, no obesity surgery, insulin-sensitive group): 9.1. No previous obesity surgery 9.2. BMI 25 - 40 kg/m^2 9.3. HOMA2-IR greater than or equal to 0.76
Key exclusion criteria	1. Inability to give formal consent 2. Unable to communicate in spoken English (due to the importance of being able to communicate while study subjects are in the scanner) 3. Age less than 18 years 4. Pregnancy, planning pregnancy, or breastfeeding 5. Currently enrolled in other clinical study 6. Left-handedness 7. Taking any glucose-lowering medications (except metformin). Subjects taking metformin will be asked to omit it the day before the Test Meal/OGTT visit and the PET scanning visits because metformin affects gastric emptying and thus may affect nutrient absorption). 8. Advanced retinopathy 9. Any significant brain disorder, e.g. previous significant head injury, epilepsy, cerebrovascular disease 10. Use of psychotropic medication, e.g. antidepressants, antipsychotics 11. Unstable angina, myocardial infarction in the previous year, uncontrolled congestive cardiac failure 12. Chronic kidney disease (Stage 3 - 5) 13. Liver function tests more than three times the upper normal limit 14. Coagulopathy (international normalised ratio [INR] greater than 1.5 or platelets less than 50 x 10^9/L) 15. Anaemia (Hb less than 10 g/dL) 16. Recent history of cancer (less than 5 years) 17. Contraindication to magnetic resonance imaging, e.g. cardiac pacemaker
Date of first enrolment	03/06/2009
Date of final enrolment	30/09/2011

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

133 Coldharbour Lane

London
SE5 9NU
United Kingdom

Sponsor information

Kings College London (KCL) (UK)
University/education

Strand
London
WC2R 2LS
England
United Kingdom

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

Funders

Funder type

Charity

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

Alternative name(s): DIABETES UK LIMITED, British Diabetic Association
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	Not provided at time of registration
IPD sharing plan

Editorial Notes

11/04/2017: No publications found, verifying study status with principal investigator.