Neuromolecular Risk Factors for Obesity (PROSPECT)
- Conditions
- Obesity
- Interventions
- Diagnostic Test: fMRI imagingDiagnostic Test: [11C]carfentanil PET scanDiagnostic Test: [18F]FMPEP-d2 PET scanDiagnostic Test: [18F]-FDG PET scanDiagnostic Test: Physical activity measures and fitness testsDiagnostic Test: Laboratory measurementsDiagnostic Test: QuestionnairesDiagnostic Test: Hyperinsulinemic euglycemic clamp
- Registration Number
- NCT03106688
- Lead Sponsor
- Turku University Hospital
- Brief Summary
The goal of this project is to characterize the neural and psychological mechanisms that contribute to development of obesity in the early adulthood. We address the neuromolecular risk factors for obesity using multi-modal molecular (positron emission tomography with) and functional (functional magnetic resonance imaging) neuroimaging in a prospective design. Normal weight adolescents with high versus low familial, genetic and psychological risk factors for obesity will be studied and followed for five years.
- Detailed Description
Diet, nutrition, and physical exercise are critical factors in the maintenance of good health through the entire life course. However, in most western countries the annual increase in the prevalence and the severity of obesity and physical inactivity is substantial. Early detection of individuals with high risk for obesity is important, because reversing the obese state is very difficult. To prevent and treat obesity, it is necessary to characterize neural mechanisms supporting altered incentive motivation and food intake, and to build a comprehensive model of the interactions between neural, physiological, and psychological factors contributing to development and maintenance of obesity. This obviously calls for novel data analysis techniques allowing fusion analysis of neurobiological, physiological, and behavioural data, as well as screening the critical combination of biomarkers for obesity.
A total of sixty males (30 normal-weight, 30 with risk for developing obesity) are recruited into this prospective study. The subjects will undergo physical examination, physical fitness tests, physical activity measures, body tissue composition measurement, structural and functional magnetic resonance imaging of the brain and body (MRI \& fMRI), and positron emission tomography (PET) with ligands \[18F\]-fluorodeoxyglucose (\[18F\]-FDG), \[18-F\]FMPEP, and \[11C\]carfentanil. Subjects' weight and physical condition will be followed up for 5 years.
In three interconnected work packages (WPs) we test three hypotheses derived from human and animal studies:
1. Altered reward and cognitive control functions in the brain predisposes some individuals to overeating and obesity.
2. Opioid system and reward circuit function provide feasible biomarkers for obesity risk.
3. Mobile tracking and behavioural paradigms tapping reward learning and inhibitory control can be used for unobtrusive and inexpensive detection of risk factors for obesity.
These studies will improve our understanding of the neural and psychological mechanisms of obesity and addictive disorders. This knowledge will translate into crucial knowledge for developing novel risk factor screening procedures, and novel pharmacological and psychological treatments for obesity.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- Male
- Target Recruitment
- 60
Inclusion criteria for low-risk group:
- Male sex
- Age 20-35 years
- BMI 20-24 kg/m2
- Physical exercise > 4 hrs per week
- No maternal / paternal obesity OR maternal / paternal type 2 diabetes mellitus (T2DM)
Inclusion criteria for high-risk group:
- Male sex
- Age 20-35 years
- BMI 25 - 30 kg/m2
- Maternal / paternal obesity OR maternal / paternal T2DM
- Physical exercise < 4 hrs per week
- Any chronic disease or medication that could affect glucose metabolism or neurotransmission
- History of anorexia nervosa, bulimia or other eating disorder (excl. common obesity)
- Smoking of tobacco, taking of snuffs, or use of narcotics
- Abusive use of alcohol
- Any other condition that in the opinion of the investigator could create a hazard to the subject safety, endanger the study procedures or interfere with the interpretation of study results
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Low-risk group [11C]carfentanil PET scan Individuals in the low-risk group are not in a risk of developing obesity according to traditional risk criteria. Low-risk group fMRI imaging Individuals in the low-risk group are not in a risk of developing obesity according to traditional risk criteria. Low-risk group Laboratory measurements Individuals in the low-risk group are not in a risk of developing obesity according to traditional risk criteria. High-risk group [18F]-FDG PET scan Individuals in the high-risk group are in a risk of developing obesity according to traditional risk criteria. High-risk group Physical activity measures and fitness tests Individuals in the high-risk group are in a risk of developing obesity according to traditional risk criteria. High-risk group Laboratory measurements Individuals in the high-risk group are in a risk of developing obesity according to traditional risk criteria. Low-risk group [18F]-FDG PET scan Individuals in the low-risk group are not in a risk of developing obesity according to traditional risk criteria. Low-risk group Physical activity measures and fitness tests Individuals in the low-risk group are not in a risk of developing obesity according to traditional risk criteria. High-risk group [18F]FMPEP-d2 PET scan Individuals in the high-risk group are in a risk of developing obesity according to traditional risk criteria. Low-risk group [18F]FMPEP-d2 PET scan Individuals in the low-risk group are not in a risk of developing obesity according to traditional risk criteria. High-risk group [11C]carfentanil PET scan Individuals in the high-risk group are in a risk of developing obesity according to traditional risk criteria. High-risk group Questionnaires Individuals in the high-risk group are in a risk of developing obesity according to traditional risk criteria. High-risk group Hyperinsulinemic euglycemic clamp Individuals in the high-risk group are in a risk of developing obesity according to traditional risk criteria. Low-risk group Questionnaires Individuals in the low-risk group are not in a risk of developing obesity according to traditional risk criteria. Low-risk group Hyperinsulinemic euglycemic clamp Individuals in the low-risk group are not in a risk of developing obesity according to traditional risk criteria. High-risk group fMRI imaging Individuals in the high-risk group are in a risk of developing obesity according to traditional risk criteria.
- Primary Outcome Measures
Name Time Method Neuromolecular risk score for weight gain Within five study years Acquired with combining the measured BMI change in five years to measured alterations in brain function (see below).
- Secondary Outcome Measures
Name Time Method BMI change in five years Within five study years Acquired with BMI of the study subjects measured in initial health check-up and once in every study year
Physical strength Within one study day Total physical strenght score is calculated from 1) countermovement jump test with a contact mat (flight time measured - jump height calculated), hand grip strength (measured in Newtons), sit-ups (number of repetitions in 30 s), and back extension (reps in 30 s)
Brain and body glucose uptake Within one study day Acquired with PET imaging
Brain MOR availability Within one study day Acquired with PET imaging
Behavioural patterns involving dysfunctional reward learning and inhibitory control Within one study year Acquired with following questionnaires: assessment of leisure-time physical activity (LTPA), Behavioural inhibition / activation, Dutch Eating Behaviour Questionnaire, Yale Food Addiction Scale, PCL-Revised, Food craving State / Trait (FCS-FCST) questionnaires, Autism Spectrum Quotient, State-Trait Anxiety Questionnaire, Pain Sensitivity Questionnaire, DASS-21, PSS-10
Body adiposity Within one study day Acquired with BodPod device (Frisard, Greenway, \& DeLany, 2005)
Genes regulating MOR (OPRM1) and D2R (DRD2) expression Within one study week Acquired with whole blood sample and DNA/RNA analysis
Brain and body CB1 availability Within one study day Acquired with PET imaging
Localization of on-going neural activity during various cognitive and affective tasks Within one study day Acquired with fMRI imaging
Genetic risk score from all known obesity-risk genes Within one study week Acquired with whole blood sample and DNA/RNA analysis
Maximal physical performance Within one study day The subjects will perform a maximal aerobic exercise test on a bicycle ergometer starting at the intensity of 50 W and followed by an increase of 30 W every 2 min until volitional exhaustion. Peak workload will be calculated as an average workload during the last 2 min of the test (weighted average will be used if the final stage is stopped prior the completion) and used as a measure of maximal performance of the subjects
Physical activity level Within one study week Acquired with Polar M600 GPS Sports Watch that study subjects wear for the measurement period
Trial Locations
- Locations (1)
Turku PET Centre (Turku University Hospital)
🇫🇮Turku, Finland