Clinical trial NCT05437653: MRI Based Study to Assess Brain-gut Axis in Obesity
Official title: Developing Magnetic Resonance Imaging Techniques to Explore the Brain-gut Axis to Food Intake in People With Obesity and Healthy Weight Participants
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Obesity
Keywords: obesity
brain-gut axis
functional magnetic resonance imaging
gastric emptying
small bowel water content
high fat meal
carbohydrate meal
Blood-oxygen-level-dependent
cerebral blood flow
resting state fMRI
Lead sponsor: University of Nottingham
Sponsor class: OTHER
First posted: 2022-06-29
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomised parallel trial in human volunteers. Control (normal weight) group VS Obese group and High fat drink VS iso-caloric, iso-viscous Carbohydrate drink
Primary purpose: BASIC_SCIENCE

Brief summary: The mechanism of neural communication between the brain and gut in the regulation of food intake is complex and not fully understood. Magnetic Resonance Imaging (MRI) is a powerful non-invasive imaging tool that allows studying the function of the brain and gut. The aim of this study is to develop MRI methods to combine brain and gut imaging in a single MRI scan session. The developed techniques will then be used to assess the brain-gut axis to a high fat drink compared with iso-caloric/iso-viscous/iso-volumetric carbohydrate drink in people with obesity and healthy weight participants. The findings could provide a possible explanation for why some people are heavier than others.

Detailed description: 20 healthy weight participant (18 Kg/m2\>BMI\<30Kg/m2) and 20 age- and sex- matched peoples with obesity (BMI \>30 Kg/m2) will be invited to a double-blinded two-way crossover MRI study, approximately 1 week apart, to assess the interplay between brain and gut to food intake.

Brain and gut MRI scans will be collected at fasted/baseline and at different time points postprandial for 120 mins using the 3T Ingenia Philips scanner. Brain measurements including resting state-fMRI, cerebral blood flow (CBF), and task-fMRI scans will be collected. During the task fMRI scan, images of high and low energy food pictures, and non-food control pictures will be presented. Food images are extensively used in fMRI studies to characterise the neural systems involved in processing the hedonic value of food as well as satiety and hunger signals. In addition to brain scans, sequences of gut scans will be collected to assess gastric volume, small bowel water content, and superior mesenteric artery (SMA) responses pre- and post-prandial. Blood samples will be collected to assess gut hormones (CCK, GLP1- PYY, ghrelin) insulin and glucose, triglycerides, free fatty acid levels at different timepoints. In addition, satiety and appetite scores will be collected using visual analogue scales. The total scan time including the fed and break times is around 3 hours.

Eligibility criteria: Inclusion Criteria:

* Aged 18-45, male and female (females will have the study days arranged during the early phase of the menstrual cycle).
* Body mass index (BMI): normal weight participants ≥ 19 and ≤ 25 Kg/m2, and obese participants \> 30 Kg/m2
* Able to give voluntary written informed consent to participate in the study
* Able to understand the requirements of the study
* Apparently healthy: no medical conditions which might affect study measurements (judged by health questionnaire, and blood screening)

Exclusion Criteria:

* Any reported history of neurological or gastrointestinal disorders
* Any reported history of surgery that could affect gastrointestinal function (e.g. colectomy, small bowel resection)
* Abnormal screening procedures including depression and eat restriction
* Laboratory results that are clinically significant, including diabetes, dyslipidemia, pancreatitis, or untreated hypertension.
* Contraindications for MRI scanning i.e. metallic implants, pacemakers, history of metallic foreign body in eye(s) and penetrating eye injury, assessed by standard MRI safety questionnaire.
* Under medication (expect aspirin/paracetamol), antibiotic or prescribed probiotic treatment in the past 12 weeks.
* Following a medically- or self-prescribed diet during the two weeks prior to the pre-study examination and until the end of the study.
* Reported weight loss or gain ≥ 10 % of bodyweight during the six months period before the pre-study examination
* Pregnancy or breastfeeding declared by candidate
* Smoking
* Left-handed assessed by handedness questionnaire. This is to control for brain's lateralisation effects (activation in one side of the brain) that may show variations between left and right handed participants.
* Participation in another clinical or research study within the previous 3 months of the study
* Cannot lie flat or exceeding the scanner bed weight limit of 250 kg.
* Poor understanding of the spoken and/or written English language

Primary outcomes:
measure: Changes in appetite- and satiety-related brain responses between drinks ( Fat drink VS Carbohydrate drink) and across groups (Healthy weight VS obese)
timeFrame: From baseline to up to 2 hours after ingesting the drinks
measure: Changes in Cerebral blood flow between drinks (Fat drink VS Carbohydrate drink) and across groups (Healthy weight VS Obese)
timeFrame: From baseline to up to 2 hours after ingesting the drinks
measure: Changes resting state brain networks between drinks (Fat drink VS Carbohydrate drink) and across groups (Healthy weight VS Obese)
timeFrame: From baseline to up to 2 hours after ingesting the drinks
measure: Changes in gastric volume between drinks (Fat drink VS Carbohydrate drink) and across groups (Healthy weight VS Obese)
timeFrame: From baseline to up to 2 hours after ingesting the drinks
measure: Correlations between gut and brain responses to assess alterations in brain-gut axis between drinks (Fat drink VS Carbohydrate drink) and across groups (Healthy weight VS Obese)
timeFrame: From baseline to up to 2 hours after ingesting the drinks
Secondary outcomes:
measure: Changes in small bowel water content between drinks (Fat drink VS Carbohydrate drink) and across groups (Healthy weight VS Obese)
timeFrame: From baseline to up to 2 hours after ingesting the drinks
measure: Changes in satiety and appetite regulators between drinks (Fat drink VS Carbohydrate drink) and across groups (Healthy weight VS Obese)
timeFrame: From baseline to up to 2 hours after ingesting the drinks
measure: Changes in satiety and appetite score (VAS) between drinks (Fat drink VS Carbohydrate drink) and across groups (Healthy weight VS Obese)
timeFrame: From baseline to up to 2 hours after ingesting the drinks
measure: Correlations between blood, brain and gut and satiety date
timeFrame: From baseline to up to 2 hours after ingesting the drinks
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: University of Nottingham
Study officials:
affiliation: University of Nottingham
name: Sally Eldeghaidy, PhD
role: PRINCIPAL_INVESTIGATOR
References: