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

NCT05080205 | Unknown

• 2 other identifiers: BariBrain-PETT153/2018
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Morbid obesity is associated with decreased brain µ-opioid receptor availability, possibly resulting in higher food intake needed to gain pleasure from eating. This decrease seems to normalize already 6 months after bariatric surgery, but the longer-term effects have not been studied. Obesity and insulin resistance result in significantly increased brain insulin-stimulated glucose uptake, whereas in every other tissue glucose uptake is lower. 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. Obesity has also been shown to associate with increased risk of Alzheimer's disease and cognitive decline in several studies. Aims: The first objective of this study is to both study the effects of bariatric surgery as well as compare the effects of gastric bypass and sleeve gastrectomy on food-associated pleasure, extending the follow-up period to 2 years postoperatively. The second aim is to investigate the effect of morbid obesity and weight loss on brain inflammation and gliosis and its association with increased brain insulin-stimulated glucose uptake. Furthermore, association of obesity, insulin resistance, central inflammation and neurocognitive dysfunction are evaluated.

Conditions

Obesity, Morbid; Insulin Resistance

Keywords

obesity; insulin resistance; central nervous system inflammation; bariatric surgery

Outcome Measures

Primary Outcomes (1)

• Change in central inflammation

  Assessment of brain glial cell activation using \[11C\]-PK11195 tracer and positron emission tomography

  Controls: 0 months; Morbidly obese: preoperatively, 6 months postoperatively

Secondary Outcomes (5)

• Changes in central reward system using fMRI imaging

  Controls: 0 months; Morbidly obese: preoperatively, 6 months, 12 months, 24 months postoperatively

• Changes in brain μ-opioid receptor availability using PET imaging

  Controls: 0 months; Morbidly obese: preoperatively, 6 months, 12 months postoperatively

• Changes in cognitive function studied with testing

  Controls: 0 months; Morbidly obese: preoperatively, 6 months, 12 months, 24 months postoperatively

• Changes in whole-body insulin sensitivity usign FDG-PET imaging

  Controls: 0 months; Morbidly obese: preoperatively, 6 months postoperatively

• Changes in tissue-specific insulin sensitivity using FDG-PET imaging

  Controls: 0 months; Morbidly obese: preoperatively

Study Arms (2)

Morbidly obese subjects

EXPERIMENTAL

Bariatric surgery (Roux-en-Y gastric bypass or sleeve gastrectomy)

Procedure: Bariatric surgery

Control subjects

NO INTERVENTION

Non-obese controls are only studied at baseline

Interventions

Bariatric surgery PROCEDURE

Roux-en-Y gastric bypass or sleeve gastrectomy, chosen based on routine evaluation process

Also known as: Roux-en-Y gastric bypass, Sleeve gastrectomy

Morbidly obese subjects

Eligibility Criteria

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

You may qualify if:

• Morbidly obese group
• BMI 35.0-45.0 kg/m2, or BMI 32.0-45.0 kg/m2 and diagnosed diabetes
• Age 18-60 years
• Eligible to bariatric surgery evaluated according to normal treatment paradigm
• Non-obese controls
• BMI 18-27 kg/m2
• Age 18-60 years
• Fasting plasma glucose ≤6.1 mmol/L
• Normal values in 2-hour oral glucose tolerance test

You may not qualify if:

• Morbidly obese group
• Metal objects in the body (including pacemakers, metallic artificial valve prostheses, inner ear implants, surgical clipses, 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.
• Non-obese controls
• Metal objects in the body (including pacemakers, metallic artificial valve prostheses, inner ear implants, surgical clipses, braces, foreign fragments)
• Previous participation in PET studies
• Pregnancy
• Poor compliance, alcohol or drug abuse
• Smoking
• History of eating disorders, drastic weight-gain or weight-loss

Sponsors & Collaborators

• Turku University Hospital: lead

Study Sites (1)

Turku PET Centre

Turku, 20520, Finland

Location

MeSH Terms

Conditions

Obesity, Morbid; Insulin Resistance; Obesity

Interventions

Bariatric Surgery; Gastric Bypass

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases

Intervention Hierarchy (Ancestors)

Bariatrics; Obesity Management; Therapeutics; Surgical Procedures, Operative; Gastroenterostomy; Anastomosis, Surgical; Digestive System Surgical Procedures

Study Officials

• Pirjo Nuutila, MD, PhD

  Turku University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Model Details: 60 subjects undergoing bariatric surgery (either Roux-en-Y gastric bypass or Sleeve gastrectomy) and 30 healthy controls

Study Record Dates

• First Submitted: June 6, 2018
• First Posted: October 15, 2021
• Study Start: February 11, 2019
• Primary Completion: October 10, 2021
• Study Completion: December 1, 2022
• Last Updated: October 15, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR

Locations

FI (1)