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

NCT04343469 | Unknown

• 1 other identifier: T26/2019
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Morbid Obesity

Keywords

positron emission tomography; magnetic resonance imaging; euglycaemic hyperinsulinemic clamp; astrogliosis; central inflammation; bariatric surgery

Outcome Measures

Primary Outcomes (2)

• Obese have brain inflammation compared to healthy ones

  Brain PET-\[11C\]-PK11195 imaging study of obese and healthy lean ones

  Both groups at baseline

• 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 Outcomes (6)

• Tissue-specific and whole-body insulin sensitivity are decreased in obese

  Baseline obese and leans

• Tissue-specific and whole-body glucose improves after bariatric surgery

  PET imaging studies at baseline and 6 months after operation

• Brain neural activity decreased in obesity

  Baseline obese and leans

• Brain neural activity improves after bariatric surgery

  Baseline and 6 months after operation (obese group)

• Brain metabolite concentrations are different in obese

  Baseline obese and leans

Study Arms (2)

Bariatric surgery

ACTIVE COMPARATOR

The effect of bariatric surgery (RYGB or LSG) on central inflammation

Procedure: Bariatric Surgery (RYGB or LSG)

No intervention

NO INTERVENTION

Healthy lean volunteers

Interventions

Bariatric Surgery (RYGB or LSG) PROCEDURE

Morbidly obese subjects will receive either RYGB or LSG, and the effect of bariatric surgery-induced weight loss on brain inflammation will be assessed

Bariatric surgery

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may not qualify if:

• Metal objects in the body (including pacemakers, metallic artificial valve prostheses, inner ear implants, surgical clips, braces, foreign fragments)
• Previous participation in PET studies
• Pregnancy
• Poor compliance, alcohol or drug abuse
• Weight over 150 kg or waist circumference over 150 cm
• Diabetes with fasting glucose levels ≥7.0 mmol/L, or treatment with insulin
• 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:
• BMI 18-27 kg/m2
• Fasting plasma glucose ≤6.1 mmol/L
• Normal values in 2-hour oral glucose tolerance test
• Metal objects in the body (including pacemakers, metallic artificial valve prostheses, inner ear implants, surgical clips, braces, foreign fragments)
• Previous participation in PET studies
• Pregnancy
• Poor compliance, alcohol or drug abuse

Sponsors & Collaborators

• Turku University Hospital: lead

Study Sites (2)

Turku PET Centre

Turku, 20520, Finland

Location

Turku University Hospital

Turku, 20520, Finland

Location

MeSH Terms

Conditions

Obesity, Morbid; Gliosis

Interventions

Bariatric Surgery

Condition Hierarchy (Ancestors)

Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pathologic Processes

Intervention Hierarchy (Ancestors)

Bariatrics; Obesity Management; Therapeutics; Surgical Procedures, Operative

Study Officials

• Pirjo Nuutila, MD, PhD

  Turku UH

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Obese and healthy ones are compared at baseline and obese are compered to healthy ones 6 months after bariatric surgery.

Study Record Dates

• First Submitted: October 7, 2019
• First Posted: April 13, 2020
• Study Start: February 11, 2019
• Primary Completion: September 1, 2022
• Study Completion: September 1, 2022
• Last Updated: October 13, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

FI (2)