Understanding How Gut and Brain Barriers Are Linked to Inflammation in Obesity (GUTBBB)

University Hospital, Gentofte, Copenhagen

Status

Invitation-only

Conditions

Systemic Inflammation Markers

Neurodegenerative Disease

Blood Brain Barrier

Intestinal Barrier Dysfunction

Obesity (Disorder)

Study type

Observational

Funder types

Other

Identifiers

NCT06787001

GUTBBB

Details and patient eligibility

About

The goal of this observational study is to understand how obesity affects the function of the gut and blood-brain barriers in adults. These barriers protect the body and brain from harmful substances, and changes in their function may lead to inflammation and increased risk of chronic diseases. The study will include 25 participants with obesity (BMI over 35) and 25 healthy participants (BMI 20-25) matched by age and gender.

The main questions it aims to answer are:

How does obesity affect the blood-brain barrier and its connection to cognitive and psychopathological status?
Does increased gut permeability lead to higher inflammation levels?
Does obesity increase the permeability of the gut barrier?

Researchers will compare results from participants with obesity to healthy participants to determine how obesity impacts barrier function, inflammation, and overall health.

Participants will:

Attend three visits over several days, including:

Screening visit: A health examination with weight, height, blood pressure, blood tests, and a scan to assess body fat distribution.
Visit 1: Provide a stool sample, drink a sugar solution to assess gut permeability, collect urine samples, and take cognitive as well as psychopathological tests.
Visit 2: Undergo an MRI scan to assess the blood-brain barrier and its function.

The study aims to identify how obesity-related changes in these barriers contribute to health risks.

Full description

The study is a cross-sectional study including individuals with obesity and lean healthy controls. It is planned to recruit 25 individuals with a BMI above 35 kg/m2 and 25 lean healthy gender- and age-matched individuals with a BMI between 20-25 kg/m2. Given the extensive nature of these examinations, which include the lactulose/sucralose-mannitol test, DCE-MRI, metabolic and cognitive assessments, they will be conducted on three separate study days, in random order, and with fixed time intervals between each study day. The study employs a comprehensive approach to assess gut barrier integrity using the lactulose/sucralose-mannitol test to evaluate barrier permeability and absorptive surface area, complemented by measuring biomarkers related to gut integrity and microbial-immune interaction. Additionally, the study analyses circulating proinflammatory biomarkers and microbial genetic material to understand systemic inflammation and bacterial translocation in obesity. The integrity of the BBB is examined using DCE-MRI to detect alterations in obesity and investigate correlation between BBB permeability and obesity-related neurological conditions. Cognitive functions are assessed through tests that evaluate domains like processing speed and memory and psychopathological tests will evaluate depressive and anxiety symptoms. These tests explore the potential impact of obesity on the central nervous system. Metabolic and physiological measurements, including glucose levels, haemoglobin A1c, and body composition, provide insights into the metabolic effects of obesity and its broader physiological implications.

Enrollment

50 estimated patients

Sex

All

Ages

40 to 70 years old

Volunteers

Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria for individuals living with obesity

BMI > 35 kg/m2, bioimpedance-assessed body fat > 30% (men) or > 40% (women), and hip/waist-ratio > 0.85
Age ≥40 and ≦70 years
Sterilised or postmenopausal women (> 12 months amenorrhoea or females ≥ 60 years of age) or women who are sexually abstinent during the entire study period or are practicing non-hormonal contraception (no contraceptive pill, no hormonal intrauterine device) during the entire study period
Able to understand written participant information and give signed informed consent.

Inclusion criteria for lean healthy controls

BMI 20-25 kg/m2, bioimpedance-assessed body fat < 30% (men) or < 40% (women), and hip/waist-ratio < 0.85
Age ≥40 and ≦70 years
Sterilised or postmenopausal women (> 12 months amenorrhoea or females ≥ 60 years of age) or women who are sexually abstinent during the entire study period or are practicing non-hormonal contraception (no contraceptive pill, no hormonal intrauterine device) during the entire study period

Exclusion Criteria:

Diagnosis of diabetes mellitus type 1 or type 2.
Inflammatory gastrointestinal conditions such as Crohn's disease, ulcerative colitis, clinically significant food allergies, candidiasis, etc.
Previous bariatric surgery, or surgeries involving the removal of intestinal tissue
The use of weight loss-inducing medication such as GLP-1 receptor agonists, bupropion/naltrexone, and orlistat within 90 days prior to screening
Planned elective surgery during the study period with the exception of dermatosurgical, ENT (ear, nose, throat) or dental procedures not requiring general anaesthesia and/or perioperative antibiotic treatment
Chronic systemic inflammatory diseases (e.g. rheumatoid arthritis) and other conditions significantly affecting inflammation status or immunoregulation (severe allergies, status post transplantation etc.)
History of sleep disorders
Chronic infectious diseases such as hepatitis, HIV etc.
Use of proton pump inhibitors, metformin, anti-biotic, lipid-lowering statins, laxatives, antihistamines, paracetamol, aspirin, statins, tricyclic antidepressants, selective serotonin reuptake inhibitor antidepressants and any other medications correlated to changes in faecal microbiome diversity for the period of the study and within 20 days prior to screening
Active use of nicotine products, including but not limited to cigarettes, vapes, or any other form of nicotine consumption.
Abuse of alcohol and/or drugs, or any other co-existing conditions that will make the individual unsuitable to participate in the study, as deemed by the investigators
Pregnancy or desire to become pregnant during the study period
Breastfeeding
Any concomitant disease or treatment that, at the discretion of the investigators, might jeopardise the participant's safety during the study
Mental incapacity or language barriers that preclude adequate understanding or cooperation, or unwillingness to comply with study requirements
Body weight above the MRI scanner's maximum capacity of 140 kg or claustrophobia at a level, which makes MRI scans impossible
Severe kidney disease with increased serum creatinine and low estimated glomerular filtration rate (GFR) (<60ml/min/1.73m2)
Magnetic foreign objects in the body (e.g. pacemaker, metal implants from operation, etc.)
Adherence to a restrictive diet (e.g. ketogenic diet, vegan diet, raw diet, low FODMAP diet, and paleo diet) which is significantly correlated to changes in faecal microbiome diversity 7.2.3. Criteria for discontinuation in the study
Withdrawal of informed consent
Pregnancy
Any safety consideration as assessed by the investigators
Any exclusion criterion developing or being diagnosed during the course of the study
Non-compliance with the study protocol as deemed by the investigators