Contact information
Type
Scientific
Primary contact
Dr Katharine Hunt
ORCID ID
Contact details
133 Coldharbour Lane
London
SE5 9NU
United Kingdom
-
katharine.f.hunt@kcl.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
7405
Study information
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
Acronym
DRN 381 (RYGB)
Study hypothesis
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
MREC approved, ref: 08/H0801/152
Study design
Single-centre observational screening cross-sectional study
Primary study design
Observational
Secondary study design
Cross sectional study
Trial setting
Hospitals
Trial type
Screening
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
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
Phase
Not Specified
Drug names
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 trial start date
03/06/2009
Overall trial end date
30/09/2011
Reason abandoned (if study stopped)
Eligibility
Participant 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
Participant type
Mixed
Age group
Adult
Gender
Both
Target number of participants
Planned sample size: 48; UK sample size: 48
Participant 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
Recruitment start date
03/06/2009
Recruitment end date
30/09/2011
Locations
Countries of recruitment
United Kingdom
Trial participating centre
133 Coldharbour Lane
London
SE5 9NU
United Kingdom
Sponsor information
Organisation
Kings College London (KCL) (UK)
Sponsor details
Strand
London
WC2R 2LS
United Kingdom
Sponsor type
University/education
Website
Funders
Funder type
Charity
Funder name
Diabetes UK (UK)
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
United Kingdom
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
Basic results (scientific)
Publication list