NCT03106688

Neuromolecular Risk Factors for Obesity (PROSPECT)

Detecting Neuromolecular Risk Factors for Obesity

• Status: Unknown
• Phase: N/A
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Turku University Hospital · Other Government
• Sex: Male
• Age: 20 Years – 35 Years
• Healthy volunteers: Accepted

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.

Conditions

• Obesity

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	fMRI imaging	Using blood oxygenation level dependent (BOLD) echo-planar imaging, fMRI will be used for characterising individual differences in the brain circuits.
DIAGNOSTIC_TEST	[11C]carfentanil PET scan	\[11C\]carfentanil is used to measure μ-opioid receptor (MOR) availability in brain.
DIAGNOSTIC_TEST	[18F]FMPEP-d2 PET scan	\[18F\]FMPEP-d2 is used to measure cannabinoid receptor type 1 (CB1) availability in brain and body.
DIAGNOSTIC_TEST	[18F]-FDG PET scan	Brain and body insuin stimulated glucose uptake is measured with radioligand \[18F\]-FDG.
DIAGNOSTIC_TEST	Physical activity measures and fitness tests	Physical activity will be measured over one week following the screening check-up, before the PET measurement days. For the measurement, subjects will wear Polar M600 GPS Sports Watch for the measurement period. The fitness tests will be performed at the Paavo Nurmi Centre.
DIAGNOSTIC_TEST	Laboratory measurements	Weight, height, blood pressure, medical history, and current medication are determined. Body fat percentage will be assessed using BodPod plethysmograph.
DIAGNOSTIC_TEST	Questionnaires	All the participants will complete a self-administered questionnaire at baseline, and at 12 months, for assessment of leisure-time physical activity (LTPA). The following questionnaires will be completed: 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 and Pain Sensitivity Questionnaire.
DIAGNOSTIC_TEST	Hyperinsulinemic euglycemic clamp	Low-dose hyperinsulinemic euglycemic clamp technique will be used to promote glucose uptake and measure insulin sensitivity of the subjects. In the clamp study subjects are administered intravenous insulin at a steady rate of 0.25 mU/kg/min and normoglycemia is maintained using a variable rate infusion of 20 % glucose based on plasma glucose measurements, which are performed every 5-10 min from arterialized venous blood.

Timeline

• Start date: 2017-04-04
• Primary completion: 2022-12-01
• Completion: 2022-12-01
• First posted: 2017-04-10
• Last updated: 2021-12-17

Locations

1 site across 1 country: Finland