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

NCT06787001 | Completed

• 1 other identifier: GUTBBB
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Obesity (Disorder); Systemic Inflammation Markers; Intestinal Barrier Dysfunction; Blood Brain Barrier; Neurodegenerative Disease

Keywords

intestinal barrier function; blood brain barrier function; microbiome; systemic inflammation; bacterial translocation

Outcome Measures

Primary Outcomes (1)

• BBB permeability

  Differences in BBB permeability using Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) between individuals with and without obesity

  25 minutes post contrast administration

Secondary Outcomes (26)

• Correlation between BBB permeability and gut barrier permeability

  25 minutes post contrast administration and 0-5h Lactulose/Mannitol ratio

• Correlation between BBB permeability and gut barrier permeability

  25 minutes post contrast administration and 5-24h Lactulose/Mannitol ratio

• Correlation between BBB permeability and gut barrier permeability

  25 minutes post contrast administration and baseline (fasting) Zonulin

• Correlation between BBB permeability and gut barrier permeability

  25 minutes post contrast administration and baseline (fasting) Citrulline

• Correlation between BBB permeability and gut barrier permeability

  25 minutes post contrast administration and baseline (fasting) Regenerating islet-derived protein 3-alpha

Study Arms (2)

Individuals living with obesity

BMI \> 35 kg/m2, bioimpedance-assessed body fat \> 30% (men) or \> 40% (women), and hip/waist-ratio \> 0.85

Individuals with lean bodies

BMI 20-25 kg/m2, bioimpedance-assessed body fat \< 30% (men) or \< 40% (women), and hip/waist-ratio \< 0.85

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Older individuals with and without obesity

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Gentofte, Copenhagen: lead
• University of Copenhagen: collaborator

Study Sites (1)

Herlev Gentofte Hospital

Hellerup, 2900, Denmark

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

whole blood, plasma, urine, feces

MeSH Terms

Conditions

Obesity; Neurodegenerative Diseases

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Nervous System Diseases

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assoc. Prof.

Study Record Dates

• First Submitted: January 9, 2025
• First Posted: January 22, 2025
• Study Start: April 1, 2025
• Primary Completion: February 17, 2026
• Study Completion: February 17, 2026
• Last Updated: February 18, 2026

Record last verified: 2026-02

Locations

DK (1)