Effects of Morbid Obesity and Bariatric Surgery on Brain Inflammation, and Activation of Central Reward System

Morbid Obesity Clinical Trial

— BARIBRAIN  

Official title:

Effects of Morbid Obesity and Bariatric Surgery on Brain Inflammation, Insulin Resistance and Activation of Central Reward System Studied Using PET- and MRI-imaging

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04343469
• Other study ID #: T26/2019
• Status: Active, not recruiting
• Phase: N/A
• Start date: February 11, 2019
• Est. completion date: September 2022

Study information

• Verified date: October 2021
• Source: Turku University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Background: The investigators have found that obesity and insulin resistance result in significantly increased brain insulin-stimulated glucose uptake, whereas in every other tissue glucose uptake is lower in the obese compared to lean individuals. One possible explanation to this could be central inflammation and activation of brain glial cells, which has been shown to occur in animal models of obesity.

Aims: The objective of this study is to investigate whether there is brain inflammation in human obesity, and whether weight loss following bariatric surgery decreases brain inflammation.

Methods: A total of 60 morbidly obese subjects, assigned for Roux-en-Y gastric bypass or for sleeve gastrectomy according to routine treatment protocols will be recruited for this study. A control group of 30 healthy subjects will also be recruited. The following studies will be performed to patients and healthy subjects: 1) structural MRI and MRS, 2) functional MRI, 3) PET imaging of cerebral inflammation and astrocyte activation using [11C]-PK11195, 4) measurement of whole-body and tissue insulin sensitivity by combining hyperinsulinemic, euglycemic clamp with [18F]-FDG-PET, 5) neuropsychological testing. The study procedures will be repeated for the morbidly obese 6 months postoperatively.

Description:

This is a prospective study, where subjects for the morbidly obese group (N=60) will be recruited from the patients undergoing bariatric surgery according to normal treatment protocol and the bariatric procedure is decided on clinical data together with the bariatric surgeon and the patient. The morbidly obese patients are studied before and 6 months after bariatric surgery.

Results of obese are compared to results of healthy subjects (N=30), who are studied once.

MRI studies: Brain structural MRI and MRS Structural brain MRI will be performed to obtain anatomical reference. The MR part of a 3T PET-MR system will be used for the study . MR spectroscopy (MRS) will be used to determine levels of different metabolites.Brain activation studies (functional MRI) The aim of the fMRI is to assess how morbid obesity and weight loss influence the brain reward system in response to visual cues (not food related); resting state fMRI will also be performed.

Brain inflammation: [¹¹C]-PK11195 tracer with PET/CT is used to determine activation of glial cells, or inflammation, in the brain. After intravenous injection of 500 MBq [¹¹C]-PK11195, a 60-minute dynamic scan on the brain using the same PET/CT cameras will be performed. Both ROI- and SPM based statistics will be used in the statistical analyses.

Whole-body scan with [18F]-FDG and PET/CT during euglycemic hyperinsulinemia used to promote tissue glucose uptake and measure insulin sensitivity. After 60 minutes from the start of clamp, the subjects will be injected intravenously with 150 MBq of [18F]-fluorodeoxyglucose ([18F]-FDG) Thereafter [18F]-fluorodeoxyglucose uptake in the brain, abdomen, femoral region will be measured.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 90
• Est. completion date: September 2022
• Est. primary completion date: September 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

For the morbidly obese subjects:

1. BMI 35.0-45.0 kg/m2, or BMI 32.0-45.0 kg/m2 and diagnosed diabetes

2. Eligible to bariatric surgery evaluated according to normal treatment paradigm

Exclusion Criteria:

1. Metal objects in the body (including pacemakers, metallic artificial valve prostheses, inner ear implants, surgical clips, braces, foreign fragments)

2. Previous participation in PET studies

3. Pregnancy

4. Poor compliance, alcohol or drug abuse

5. Weight over 150 kg or waist circumference over 150 cm

6. Diabetes with fasting glucose levels =7.0 mmol/L, or treatment with insulin

7. Any chronic disease, medication or condition that could create a hazard to subject safety, endanger study procedures or interfere with the interpretation of results.

For the lean control subjects:

Inclusion Criteria:

1. BMI 18-27 kg/m2

2. Fasting plasma glucose =6.1 mmol/L

3. Normal values in 2-hour oral glucose tolerance test

Exclusion Criteria:

1. Metal objects in the body (including pacemakers, metallic artificial valve prostheses, inner ear implants, surgical clips, braces, foreign fragments)

2. Previous participation in PET studies

3. Pregnancy

4. Poor compliance, alcohol or drug abuse

5. Smoking

6. History of eating disorders, drastic weight-gain or weight-loss

7. History of psychiatric disorders

8. Any chronic disease, medication or condition that could create a hazard to subject safety, endanger study procedures or interfere with the interpretation of results

Related Conditions & MeSH terms

• Encephalitis
• Inflammation
• Morbid Obesity
• Obesity
• Obesity, Morbid

Intervention

Procedure:
• Bariatric Surgery (RYGB or LSG)
Morbidly obese subjects will receive either RYGB or LSG, and the effect of bariatric surgery-induced weight loss on brain inflammation will be assessed

Locations

Country	Name	City	State
Finland	Turku PET Centre	Turku
Finland	Turku University Hospital	Turku

Sponsors (1)

Lead Sponsor	Collaborator
Turku University Hospital

Country where clinical trial is conducted

Finland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Obese have brain inflammation compared to healthy ones	Brain PET-[11C]-PK11195 imaging study of obese and healthy lean ones	Both groups at baseline
Primary	Bariatric surgery decreases brain inflammation in obesity	PK11195 imaging results are compared before and 6 months after bariatric surgery in obese group studied before and after bariatric surgery	Baseline and 6 months after operation (obese group only)
Secondary	Tissue-specific and whole-body insulin sensitivity are decreased in obese	Glucose uptakes are measured using PET imaging in obese and leans	Baseline obese and leans
Secondary	Tissue-specific and whole-body glucose improves after bariatric surgery	Comparison before and 6 months after surgery (obese group)	PET imaging studies at baseline and 6 months after operation
Secondary	Brain neural activity decreased in obesity	Comparison between obese and lean ones using fMRI	Baseline obese and leans
Secondary	Brain neural activity improves after bariatric surgery	Comparison between obese baseline and 6 months after operation	Baseline and 6 months after operation (obese group)
Secondary	Brain metabolite concentrations are different in obese	MRS studies for obese and lean ones at baseline are compared	Baseline obese and leans
Secondary	Brain metabolite concentrations normalize after bariatric surgery	MRS studies for obese before and 6 months postop compared	Baseline and 6 months postop (obese group)