ObesityNCT03106688
Neuromolecular Risk Factors for Obesity (PROSPECT)
A study testing fMRI imaging, [11C]carfentanil PET scan and [18F]FMPEP-d2 PET scan in people with Obesity, run by Turku University Hospital at 1 site in Finland.
Trial 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… Read more about this study
- Who is it for?
- Ages 20 to 35 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Obesity
- What is being tested?
- fMRI imaging, [11C]carfentanil PET scan and [18F]FMPEP-d2 PET scan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteFinland
- Study dates
- 4 Apr 2017to 1 Dec 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 35 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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)
- Male sex
Show all 10Show fewer
- Age 20-35 years
- BMI 25 - 30 kg/m2
- Maternal / paternal obesity OR maternal / paternal T2DM
- Physical exercise < 4 hrs per week
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Detecting Neuromolecular Risk Factors for Obesity
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.
Read the 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:
- Altered reward and cognitive control functions in the brain predisposes some individuals to overeating and obesity.
- Opioid system and reward circuit function provide feasible biomarkers for obesity risk.
- 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
- Being tested
- fMRI imaging, [11C]carfentanil PET scan, [18F]FMPEP-d2 PET scan, [18F]-FDG PET scan, Physical activity measures and fitness tests
- Keywords
- PET imaging, Cannabinoid receptor, Opioid receptor, Addiction, fMRI imaging
- Medical subject headings
- Obesity, Behavior, Addictive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
fMRI imagingDiagnostic test
Using blood oxygenation level dependent (BOLD) echo-planar imaging, fMRI will be used for characterising individual differences in the brain circuits.
[11C]carfentanil PET scanDiagnostic test
[11C]carfentanil is used to measure μ-opioid receptor (MOR) availability in brain.
[18F]FMPEP-d2 PET scanDiagnostic test
[18F]FMPEP-d2 is used to measure cannabinoid receptor type 1 (CB1) availability in brain and body.
[18F]-FDG PET scanDiagnostic test
Brain and body insuin stimulated glucose uptake is measured with radioligand [18F]-FDG.
Physical activity measures and fitness testsDiagnostic test
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.
Laboratory measurementsDiagnostic test
Weight, height, blood pressure, medical history, and current medication are determined. Body fat percentage will be assessed using BodPod plethysmograph.
QuestionnairesDiagnostic test
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.
Hyperinsulinemic euglycemic clampDiagnostic test
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.
| Study group | Role | What they receive |
|---|---|---|
| Low-risk group | Active comparator | Individuals in the low-risk group are not in a risk of developing obesity according to traditional risk criteria. Receives: Diagnostic Test: fMRI imaging; Diagnostic Test: [11C]carfentanil PET scan; Diagnostic Test: [18F]FMPEP-d2 PET scan; Diagnostic Test: [18F]-FDG PET scan; Diagnostic Test: Physical activity measures and fitness tests; Diagnostic Test: Laboratory measurements; Diagnostic Test: Questionnaires; Diagnostic Test: Hyperinsulinemic euglycemic clamp |
| High-risk group | Active comparator | Individuals in the high-risk group are in a risk of developing obesity according to traditional risk criteria. Receives: Diagnostic Test: fMRI imaging; Diagnostic Test: [11C]carfentanil PET scan; Diagnostic Test: [18F]FMPEP-d2 PET scan; Diagnostic Test: [18F]-FDG PET scan; Diagnostic Test: Physical activity measures and fitness tests; Diagnostic Test: Laboratory measurements; Diagnostic Test: Questionnaires; Diagnostic Test: Hyperinsulinemic euglycemic clamp |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neuromolecular risk score for weight gain
Acquired with combining the measured BMI change in five years to measured alterations in brain function (see below).
Measured: Within five study years
Secondary outcomes (12)
Localization of on-going neural activity during various cognitive and affective tasks
Acquired with fMRI imaging
Measured: Within one study day
Brain and body glucose uptake
Acquired with PET imaging
Measured: Within one study day
Brain and body CB1 availability
Acquired with PET imaging
Measured: Within one study day
Brain MOR availability
Acquired with PET imaging
Measured: Within one study day
Genes regulating MOR (OPRM1) and D2R (DRD2) expression
Acquired with whole blood sample and DNA/RNA analysis
Measured: Within one study week
Genetic risk score from all known obesity-risk genes
Acquired with whole blood sample and DNA/RNA analysis
Measured: Within one study week
Behavioural patterns involving dysfunctional reward learning and inhibitory control
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
Measured: Within one study year
Physical activity level
Acquired with Polar M600 GPS Sports Watch that study subjects wear for the measurement period
Measured: Within one study week
Maximal physical performance
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
Measured: Within one study day
Physical strength
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)
Measured: Within one study day
BMI change in five years
Acquired with BMI of the study subjects measured in initial health check-up and once in every study year
Measured: Within five study years
Body adiposity
Acquired with BodPod device (Frisard, Greenway, \& DeLany, 2005)
Measured: Within one study day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2017
- Study start4 Apr 2017
- Primary completion1 Dec 2022 (estimated)
- Study completion1 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ObesityStudies of the same condition, open and under way.
- More trials run by Turku University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Turku University Hospital
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Pirjo Nuutila, Turku University Hospital
- Investigators
- Pirjo Nuutila, M.D., Ph.D., Principal investigator, Turku PET Centre (Turku University Hospital)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03106688
- Sponsor's protocol ID
- PROSPECT
- Status last verified
- Dec 2021
- First submitted
- 5 Mar 2017
- Last updated
- 17 Dec 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Frisard MI, Greenway FL, Delany JP. Comparison of methods to assess body composition changes during a period of weight loss. Obes Res. 2005 May;13(5):845-54. doi: 10.1038/oby.2005.97.
PubMed 15919837
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Detecting Neuromolecular Risk Factors for Obesity
- ClinicalTrials.gov ID
- NCT03106688
- Acronym / sponsor ID
- PROSPECT
- Conditions
- Obesity
- Keywords
- PET imaging, Cannabinoid receptor, Opioid receptor, Addiction, fMRI imaging
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Turku University HospitalOther government
- Study start
- 4 Apr 2017 (actual)
- Primary completion
- 1 Dec 2022 (estimated)
- Study completion
- 1 Dec 2022 (estimated)
- First posted
- 10 Apr 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Altered reward and cognitive control functions in the brain predisposes some individuals to overeating and obesity.
- Opioid system and reward circuit function provide feasible biomarkers for obesity risk.
- 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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Low-risk group | Active comparator | Diagnostic Test: fMRI imaging, Diagnostic Test: [11C]carfentanil PET scan, Diagnostic Test: [18F]FMPEP-d2 PET scan, Diagnostic Test: [18F]-FDG PET scan, Diagnostic Test: Physical activity measures and fitness tests, Diagnostic Test: Laboratory measurements, Diagnostic Test: Questionnaires, Diagnostic Test: Hyperinsulinemic euglycemic clampIndividuals in the low-risk group are not in a risk of developing obesity according to traditional risk criteria. |
| High-risk group | Active comparator | Diagnostic Test: fMRI imaging, Diagnostic Test: [11C]carfentanil PET scan, Diagnostic Test: [18F]FMPEP-d2 PET scan, Diagnostic Test: [18F]-FDG PET scan, Diagnostic Test: Physical activity measures and fitness tests, Diagnostic Test: Laboratory measurements, Diagnostic Test: Questionnaires, Diagnostic Test: Hyperinsulinemic euglycemic clampIndividuals in the high-risk group are in a risk of developing obesity according to traditional risk criteria. |
Who may qualify
- Ages
- 20 to 35 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- 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)
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| fMRI imagingUsing blood oxygenation level dependent (BOLD) echo-planar imaging, fMRI will be used for characterising individual differences in the brain circuits. | Diagnostic test | High-risk group, Low-risk group |
| [11C]carfentanil PET scan[11C]carfentanil is used to measure μ-opioid receptor (MOR) availability in brain. | Diagnostic test | High-risk group, Low-risk group |
| [18F]FMPEP-d2 PET scan[18F]FMPEP-d2 is used to measure cannabinoid receptor type 1 (CB1) availability in brain and body. | Diagnostic test | High-risk group, Low-risk group |
| [18F]-FDG PET scanBrain and body insuin stimulated glucose uptake is measured with radioligand [18F]-FDG. | Diagnostic test | High-risk group, Low-risk group |
| Physical activity measures and fitness testsPhysical 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 | High-risk group, Low-risk group |
| Laboratory measurementsWeight, height, blood pressure, medical history, and current medication are determined. Body fat percentage will be assessed using BodPod plethysmograph. | Diagnostic test | High-risk group, Low-risk group |
| QuestionnairesAll 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 | High-risk group, Low-risk group |
| Hyperinsulinemic euglycemic clampLow-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. | Diagnostic test | High-risk group, Low-risk group |
Primary outcome
Neuromolecular risk score for weight gain
Time frame: Within five study years
Acquired with combining the measured BMI change in five years to measured alterations in brain function (see below).
12 secondary outcomes
Localization of on-going neural activity during various cognitive and affective tasks
Time frame: Within one study day
Brain and body glucose uptake
Time frame: Within one study day
Brain and body CB1 availability
Time frame: Within one study day
Brain MOR availability
Time frame: Within one study day
Genes regulating MOR (OPRM1) and D2R (DRD2) expression
Time frame: Within one study week
Genetic risk score from all known obesity-risk genes
Time frame: Within one study week
Behavioural patterns involving dysfunctional reward learning and inhibitory control
Time frame: Within one study year
Physical activity level
Time frame: Within one study week
Maximal physical performance
Time frame: Within one study day
Physical strength
Time frame: Within one study day
BMI change in five years
Time frame: Within five study years
Body adiposity
Time frame: Within one study day
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2021.
- Background: PubMed 15919837Frisard MI, Greenway FL, Delany JP. Comparison of methods to assess body composition changes during a period of weight loss. Obes Res. 2005 May;13(5):845-54. doi: 10.1038/oby.2005.97.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pirjo Nuutila, M.D., Ph.D. principal investigator
Turku PET Centre (Turku University Hospital)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing fMRI imaging, [11C]carfentanil PET scan and [18F]FMPEP-d2 PET scan in people with Obesity, run by Turku University Hospital at 1 site in Finland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Finland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Neuromolecular risk score for weight gain (time frame: Within five study years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03106688, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2021.