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出境医 / 临床实验 / Evaluating Motivation and Reward Mechanisms and Brain Substrates in Adults With Obesity

Evaluating Motivation and Reward Mechanisms and Brain Substrates in Adults With Obesity

Study Description
Brief Summary:

Anhedonia and abnormalities in reward behavior are core features of overweight/obesity (OW), a highly prevalent condition within MDD populations, and is independently associated with reward disturbances. The investigators therefore aim to investigate the brain substrates subserving reward and motivation in adults with overweight/obesity.

The primary aim of this pilot study is to determine whether associations exist between obesity and decreased performance on the respective motivation/reward paradigms.


Condition or disease
Anhedonia Obesity

Detailed Description:

Herein, the investigators are primarily interested in three overlapping, yet distinct aspects, of anhedonia. The investigators are primarily interested in motivation, reward valuation, and reward learning towards addressing the measurement of each of these respective subdomains, eligible participants will complete validated gold standard measures (i.e. the Effort Expenditure for Rewards Task (EEfRT) (reward valuation), Probabilistic Reward Task (PRT) (reward learning), and the Monetary Incentive Delay (MID) task (reward anticipation)).

Twenty adults with overweight/obesity will complete all tasks at a single visit with two of the tasks being completed prior to MRI and one of the tasks (i.e. EEfRT) will be completed during MRI acquisition.

The primary aim of this pilot study is to determine whether associations exist between obesity and decreased performance on the respective motivation/reward paradigms. In addition, associations between performance on reward tasks and functional connectivity, as measured by MRI and DTI, a secondary objective is to ascertain whether associations exist between performance on the motivation reward tasks and gold standard measures of food intake (i.e. food diary) and energy expenditure (i.e. calorimetry).

Study Design
Layout table for study information
Study Type : Observational
Estimated Enrollment : 20 participants
Observational Model: Other
Time Perspective: Cross-Sectional
Official Title: Evaluating Motivation and Reward Mechanisms and Brain Substrates in Adults With Obesity: Further Evidence That Obesity Affects Physical and Mental Health
Actual Study Start Date : October 30, 2019
Estimated Primary Completion Date : August 1, 2020
Estimated Study Completion Date : September 1, 2020
Arms and Interventions
Group/Cohort
Major Depressive Disorder or Bipolar Disorder
All eligible participants will be included in this single study arm.
Outcome Measures
Primary Outcome Measures :
  1. Effort Expenditure for Rewards Task (EEfRT) [ Time Frame: 1 day ]
    The EEfRT task is a behavioural paradigm that is used to investigate the subject's effort-based decision-making. Subjects are presented with a series of repeated trials wherein they must choose between performing a hard task or an easy task in order to receive monetary compensation (subject's will receive greater compensation for completing the hard task and less compensation for completing the easy task). By presenting the subject with different probability levels for reward receipt, the objective is to examine the extent to which the relationship between motivation (i.e., anhedonia) and effort-based decision-making is modulated by perceived reward magnitude.

  2. Monetary Incentive Delay (MID) Task [ Time Frame: 1 day ]
    The MID is a behavioural paradigm that assesses the basis of anticipation and consumption of reward and punishment. Each run of the MID task consists of approximately 72 trials. The types of cues presented include: circles (indicating the potential to win money i.e., gain cue), squares (indicating the potential to lose money i.e., loss cue), and a triangle (indicating no money will be won or lost i.e., neutral cue). A cue is presented for 500 ms, followed by a fixation cross (2,000 to 2,500 ms) and then the target square (160 to 260 ms), during which the participant is instructed to press a button as quickly as possible to win or avoid losing money. A feedback screen (1,650 ms), in which the top number indicates the amount of money won or lost during that trial, and the bottom number indicates the participant's total amount, is presented at the end of each trial.

  3. Probablistic Reward Task (PRT) [ Time Frame: 1 day ]
    The PRT is a behavioural paradigm that measures response bias and sensitivity to reward under variable conditions. In this task, a signal detection approach is used, whereby subjects must discriminate between two non-ambiguous stimuli displayed rapidly on a computer screen in order to receive a monetary reward. Unbeknownst to the subjects, correct identification of one stimulus is reinforced three times more frequently than the other stimulus. Under these experimental circumstances, healthy subjects reliably develop a response bias for the stimulus that is reinforced more frequently, regardless of which stimulus was actually presented. Thus, reward responsiveness assessed in this task reflects the rapid shaping of future behavioral choices based on prior reinforcement experiences.


Secondary Outcome Measures :
  1. MRI/DTI [ Time Frame: 1 day ]

    The secondary outcome will be the association between the EEfRT and function reciprocity of the reward circuit/cognitive control network as measured by MRI/DTI.

    Subjects will be scanned using a 3.0-Tesla Signa HDx scanner with an 8-channel phased-array receiver coil consisting of a structural and functional neuroimaging, comprising:

    1. Whole-brain 3-D T1-weighted Inversion-Recovery prepared Fast Spoiled Gradient-Echo anatomical scan
    2. Whole-brain, T2*-weighted BOLD echo planar imaging during awake resting state
    3. Three runs of whole-brain, T2*-weighted BOLD EPI series during task-based reward paradigm.

    Graph theoretical analysis will be used to assess functional connectivity of the default mode network, cognitive control network, affect network and reward network.

    Associations between obesity and alterations in functional connectivity will be the outcome of interest.



Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Participants will be identified at the Brain and Cognition Discovery Foundation (BCDF). Twenty subjects between the ages of 18-65 years with obesity, will be enrolled. All patients will be assessed for concurrent psychiatric disorders (e.g. mood disorders) and will meet DSM-V criteria for either: major depressive disorder (symptomatic or asymptomatic in any phase of the illness) or bipolar disorder I/II (symptomatic or asymptomatic in any phase of the illness).
Criteria

Inclusion Criteria:

  • 18-65 years of age
  • Meeting DSM-V criteria for: (i) Major depressive disorder (symptomatic or asymptomatic in any phase of the illness) or (ii) bipolar disorder I/II (symptomatic or asymptomatic in any phase of the illness)
  • Ability to provide written and informed consent
  • Obesity 30 kg/m2
  • Weight under 440lbs
  • Shoulder-to-shoulder width under 60 cm

Exclusion Criteria:

  • Age below 18 or above 65
  • Use of benzodiazepines or consumption of alcohol within 12 hours of assessments
  • Abuse of marijuana
  • Physical, cognitive, or language impairments sufficient to adversely affect data derived from assessments
  • Diagnosed reading disability or dyslexia
  • Clinically significant learning disorder by history
  • History of moderate or severe traumatic brain injury
  • Other neurological disorders, or unstable systemic medical diseases
  • Pregnancy and post-partum period
  • Presence of any contra-indications for MRI
  • Weight above 440lbs
  • Shoulder-to-shoulder width greater than 60 cm.

All subjects will be consented prior to initiating the study; >45 BMI; suicidality as determined by clinical discretion

Contacts and Locations

Contacts
Layout table for location contacts
Contact: Hartej Gill, BSc 416-430-9619 hartej.gill@mail.utoronto.ca
Contact: Nelson Rodrigues, MSc 416-430-9619 nelson.rodrigues@crtce.com

Locations
Layout table for location information
Canada, Ontario
Canadian Rapid Treatment Centre of Excellence Recruiting
Mississauga, Ontario, Canada, L5C 4E7
Contact: Hartej Gill, BSc    416-430-9619    hartej.gill@mail.utoronto.ca   
Sponsors and Collaborators
Brain and Cognition Discovery Foundation
Tracking Information
First Submitted Date April 25, 2019
First Posted Date May 7, 2019
Last Update Posted Date December 24, 2019
Actual Study Start Date October 30, 2019
Estimated Primary Completion Date August 1, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: May 3, 2019)
  • Effort Expenditure for Rewards Task (EEfRT) [ Time Frame: 1 day ]
    The EEfRT task is a behavioural paradigm that is used to investigate the subject's effort-based decision-making. Subjects are presented with a series of repeated trials wherein they must choose between performing a hard task or an easy task in order to receive monetary compensation (subject's will receive greater compensation for completing the hard task and less compensation for completing the easy task). By presenting the subject with different probability levels for reward receipt, the objective is to examine the extent to which the relationship between motivation (i.e., anhedonia) and effort-based decision-making is modulated by perceived reward magnitude.
  • Monetary Incentive Delay (MID) Task [ Time Frame: 1 day ]
    The MID is a behavioural paradigm that assesses the basis of anticipation and consumption of reward and punishment. Each run of the MID task consists of approximately 72 trials. The types of cues presented include: circles (indicating the potential to win money i.e., gain cue), squares (indicating the potential to lose money i.e., loss cue), and a triangle (indicating no money will be won or lost i.e., neutral cue). A cue is presented for 500 ms, followed by a fixation cross (2,000 to 2,500 ms) and then the target square (160 to 260 ms), during which the participant is instructed to press a button as quickly as possible to win or avoid losing money. A feedback screen (1,650 ms), in which the top number indicates the amount of money won or lost during that trial, and the bottom number indicates the participant's total amount, is presented at the end of each trial.
  • Probablistic Reward Task (PRT) [ Time Frame: 1 day ]
    The PRT is a behavioural paradigm that measures response bias and sensitivity to reward under variable conditions. In this task, a signal detection approach is used, whereby subjects must discriminate between two non-ambiguous stimuli displayed rapidly on a computer screen in order to receive a monetary reward. Unbeknownst to the subjects, correct identification of one stimulus is reinforced three times more frequently than the other stimulus. Under these experimental circumstances, healthy subjects reliably develop a response bias for the stimulus that is reinforced more frequently, regardless of which stimulus was actually presented. Thus, reward responsiveness assessed in this task reflects the rapid shaping of future behavioral choices based on prior reinforcement experiences.
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: May 3, 2019)
MRI/DTI [ Time Frame: 1 day ]
The secondary outcome will be the association between the EEfRT and function reciprocity of the reward circuit/cognitive control network as measured by MRI/DTI. Subjects will be scanned using a 3.0-Tesla Signa HDx scanner with an 8-channel phased-array receiver coil consisting of a structural and functional neuroimaging, comprising:
  1. Whole-brain 3-D T1-weighted Inversion-Recovery prepared Fast Spoiled Gradient-Echo anatomical scan
  2. Whole-brain, T2*-weighted BOLD echo planar imaging during awake resting state
  3. Three runs of whole-brain, T2*-weighted BOLD EPI series during task-based reward paradigm.
Graph theoretical analysis will be used to assess functional connectivity of the default mode network, cognitive control network, affect network and reward network. Associations between obesity and alterations in functional connectivity will be the outcome of interest.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Evaluating Motivation and Reward Mechanisms and Brain Substrates in Adults With Obesity
Official Title Evaluating Motivation and Reward Mechanisms and Brain Substrates in Adults With Obesity: Further Evidence That Obesity Affects Physical and Mental Health
Brief Summary

Anhedonia and abnormalities in reward behavior are core features of overweight/obesity (OW), a highly prevalent condition within MDD populations, and is independently associated with reward disturbances. The investigators therefore aim to investigate the brain substrates subserving reward and motivation in adults with overweight/obesity.

The primary aim of this pilot study is to determine whether associations exist between obesity and decreased performance on the respective motivation/reward paradigms.

Detailed Description

Herein, the investigators are primarily interested in three overlapping, yet distinct aspects, of anhedonia. The investigators are primarily interested in motivation, reward valuation, and reward learning towards addressing the measurement of each of these respective subdomains, eligible participants will complete validated gold standard measures (i.e. the Effort Expenditure for Rewards Task (EEfRT) (reward valuation), Probabilistic Reward Task (PRT) (reward learning), and the Monetary Incentive Delay (MID) task (reward anticipation)).

Twenty adults with overweight/obesity will complete all tasks at a single visit with two of the tasks being completed prior to MRI and one of the tasks (i.e. EEfRT) will be completed during MRI acquisition.

The primary aim of this pilot study is to determine whether associations exist between obesity and decreased performance on the respective motivation/reward paradigms. In addition, associations between performance on reward tasks and functional connectivity, as measured by MRI and DTI, a secondary objective is to ascertain whether associations exist between performance on the motivation reward tasks and gold standard measures of food intake (i.e. food diary) and energy expenditure (i.e. calorimetry).

Study Type Observational
Study Design Observational Model: Other
Time Perspective: Cross-Sectional
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Probability Sample
Study Population Participants will be identified at the Brain and Cognition Discovery Foundation (BCDF). Twenty subjects between the ages of 18-65 years with obesity, will be enrolled. All patients will be assessed for concurrent psychiatric disorders (e.g. mood disorders) and will meet DSM-V criteria for either: major depressive disorder (symptomatic or asymptomatic in any phase of the illness) or bipolar disorder I/II (symptomatic or asymptomatic in any phase of the illness).
Condition
  • Anhedonia
  • Obesity
Intervention Not Provided
Study Groups/Cohorts Major Depressive Disorder or Bipolar Disorder
All eligible participants will be included in this single study arm.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: May 3, 2019)
20
Original Estimated Enrollment Same as current
Estimated Study Completion Date September 1, 2020
Estimated Primary Completion Date August 1, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • 18-65 years of age
  • Meeting DSM-V criteria for: (i) Major depressive disorder (symptomatic or asymptomatic in any phase of the illness) or (ii) bipolar disorder I/II (symptomatic or asymptomatic in any phase of the illness)
  • Ability to provide written and informed consent
  • Obesity 30 kg/m2
  • Weight under 440lbs
  • Shoulder-to-shoulder width under 60 cm

Exclusion Criteria:

  • Age below 18 or above 65
  • Use of benzodiazepines or consumption of alcohol within 12 hours of assessments
  • Abuse of marijuana
  • Physical, cognitive, or language impairments sufficient to adversely affect data derived from assessments
  • Diagnosed reading disability or dyslexia
  • Clinically significant learning disorder by history
  • History of moderate or severe traumatic brain injury
  • Other neurological disorders, or unstable systemic medical diseases
  • Pregnancy and post-partum period
  • Presence of any contra-indications for MRI
  • Weight above 440lbs
  • Shoulder-to-shoulder width greater than 60 cm.

All subjects will be consented prior to initiating the study; >45 BMI; suicidality as determined by clinical discretion

Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Hartej Gill, BSc 416-430-9619 hartej.gill@mail.utoronto.ca
Contact: Nelson Rodrigues, MSc 416-430-9619 nelson.rodrigues@crtce.com
Listed Location Countries Canada
Removed Location Countries  
 
Administrative Information
NCT Number NCT03939676
Other Study ID Numbers Pro00032575
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Dr. Roger S. McIntyre, Brain and Cognition Discovery Foundation
Study Sponsor Brain and Cognition Discovery Foundation
Collaborators Not Provided
Investigators Not Provided
PRS Account Brain and Cognition Discovery Foundation
Verification Date December 2019