Major Depressive DisorderNCT01976975
Brain Mechanisms of Human Motivation
An observational study of Major Depressive Disorder and Bipolar Disorder, run by Mclean Hospital at 1 site in United States.
Trial summary
This study aims to investigate reward learning across the mood disorder spectrum and to investigate the predictive validity of reward learning for subsequent symptom severity. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Major Depressive Disorder, Bipolar Disorder
- How many people
- 270 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2013to Jan 2018
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: We are studying a population with depressive and/or manic or hypomanic symptoms, as well as healthy controls.
Who may be able to join
- Written informed consent
- Right-handed
- (For mood disorder group only) Stable medication over the past 8 weeks OR absence of any psychotropic medications for at least 2 weeks (for follow-up analyses testing effects in medication-free patients):
- 6 weeks for fluoxetine,
- 6 months for neuroleptics,
- 2 weeks for benzodiazepines,
- 2 weeks for any other antidepressants
- 4 weeks for any mood-stabilizers
Who cannot join
- Suicidal ideation where outpatient treatment is determined unsafe by the study clinician
- Pregnant women or women of childbearing potential who 1) have not completed a negative urine pregnancy test prior to the MRI scan and/or 2) are seeking to become pregnant or believe that they may be pregnant
- Serious/unstable medical illness (e.g., cardiovascular, renal, endocrine, neurologic disease)
- Clinical or laboratory evidence of hypothyroidism
- History of seizure disorder, history or current diagnosis of dementia, score < 26 on the MMSE at screening
- History or current diagnosis of the following DSM-IV psychiatric illness: organic mental disorder, schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorder NOS, patients with mood congruent or mood incongruent psychotic features, anorexia nervosa, obsessive compulsive disorder
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- Lifetime history of stimulant dependence (e.g., cocaine, amphetamines)
- Current use of Methylphenidate (Ritalin) and other ADHD medications with dopaminergic effects
- Patients with a lifetime history of electroconvulsive therapy (ECT)
- Failure to meet standard MRI safety requirements
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Multi Level Analysis of Positive Valence Systems Across Mood Disorders
This study aims to investigate reward learning across the mood disorder spectrum and to investigate the predictive validity of reward learning for subsequent symptom severity.
Read the detailed description
The study involves five sessions. In the first session, participants will play a computer task. In the second session, participants will go through a clinical interview and will have an EEG recording while playing another computer task. In the third session, participants will undergo an fMRI scan while playing another computer task. All tasks assess reward learning. At three and six months after the final session, participants will come back for a follow-up interview session during which a clinician will assess symptom severity. There will be no intervention in this study.
- Conditions
- Major Depressive Disorder, Bipolar Disorder
- Keywords
- Depression, Major Depressive Disorder, Bipolar Disorder, Mania, Hypomania, EEG, MRI, Reward
- Medical subject headings
- Depressive Disorder, Major, Bipolar Disorder, Depression, Mania
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Mood disorder patients | Patients with depressive and/or manic or hypomanic symptoms | |
| Healthy controls | Participants with no lifetime history of psychiatric illness |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Response Bias
The Probabilistic Reward Task (PRT) is a behavioral task that measures an individual's ability to learn to choose a more rewarding outcome versus a less rewarding one (Response Bias). The response bias score is a ratio of the number of times a participant correctly chooses the high reward stimulus (the "rich" stimulus) versus the low reward stimulus (the "lean" stimulus). Response bias scores range between -1 and +1. A higher Response Bias score indicates a stronger bias toward the rich stimulus, and a negative Response Bias indicates a stronger bias toward the lean stimulus. The Change-in-Response-Bias is calculated by subtracting Response Bias in block 1 (trials 0-100) of the task from Response Bias in block 3 (trials 201-300) of the task. This metric represents the degree to which an individual is able to update behavior as a function of the asymmetrical reinforcement schedule.
Measured: Administered during the first session.
Mean Accuracy on Gain Trials During an Instrumental Learning Task
The instrumental learning task requires participants to choose between two abstract symbols. Each symbol in the pair is associated with an 80% or 20% probability of a given outcome (gain: win $1 or $0; loss: lose $1 or $0; neutral: view a gray square or see the word 'nothing'). The task consists of three blocks. Behavioral performance focuses on the number of times the participant chose the symbol that was associated more frequently associated with the more desirable outcome. A participant scores 1 if they choose correctly, and 0 if they choose in correctly, and correct choices across all three blocks are added and converted to a percentage relative to the total number of trials in that condition (i.e., gain, loss, or neutral). This study focused on percent of accuracy responses in the gain condition.
Measured: Administered in session 3 during 1.5 hour MR scan
Secondary outcomes (1)
Symptom Severity at 6 Month Follow-up
- Beck Depression Inventory (BDI-II). Severity of depressive symptoms, from 0 (no symptoms) to 63 (severely depressed)
- Young Mania Rating Scale (YMRS). Severity of manic symptoms, from 0 (not manic) to 60 (severely manic)
- Temporal Experience of Pleasure Scale (TEPS). The TEPS is an 18-item questionnaire. Ten items make up the TEPS-Anticipatory Pleasure scale with a range from 10 (not motivated) to 60 (highly motivated).
- The other eight TEPS items make up the TEPS-Consummatory Pleasure scale; range from 8 (not responsive) to 48 (highly responsive)
- Mood and Anxiety Symptom Questionnaire - Anhedonic Depression (MASQ-AD). The MASQ is a 62-item self-report on the severity of anxiety and depressive symptoms. The AD subscale is a 22-item measure of severity of anhedonic symptoms. Range: 22 -110 (higher scores mean greater severity)
- Barrett Impulsiveness Scale 11 (BIS-11): a 30-item assessment of Trait Impulsivity. Range: 30-120 (higher scores mean more impulsiveness)
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2013 (estimated)
- Study startOct 2013
- Primary completionJan 2018
- Study completionJan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 270 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mclean Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Diego A. Pizzagalli, Mclean Hospital
- Investigators
- Diego A Pizzagalli, Ph.D., Principal investigator, Mclean Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01976975
- Sponsor's protocol ID
- 2013-P-001352
- Status last verified
- Aug 2021
- First submitted
- 25 Oct 2013
- Last updated
- 4 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Pizzagalli D, Whitton A, Treadway M, Rutherford A, Kumar P, Ironside M, Kaiser R, Ren B, Dan R. Brain-based graph-theoretical predictive modeling to map the trajectory of transdiagnostic symptoms of anhedonia, impulsivity, and hypomania from the human functional connectome. Res Sq [Preprint]. 2023 Sep 28:rs.3.rs-3168186. doi: 10.21203/rs.3.rs-3168186/v1.
PubMed 37841877Whitton AE, Kumar P, Treadway MT, Rutherford AV, Ironside ML, Foti D, Fitzmaurice G, Du F, Pizzagalli DA. Distinct profiles of anhedonia and reward processing and their prospective associations with quality of life among individuals with mood disorders. Mol Psychiatry. 2023 Dec;28(12):5272-5281. doi: 10.1038/s41380-023-02165-1. Epub 2023 Jul 4.
PubMed 37402852
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multi Level Analysis of Positive Valence Systems Across Mood Disorders
- ClinicalTrials.gov ID
- NCT01976975
- Acronym / sponsor ID
- 2013-P-001352
- Conditions
- Major Depressive Disorder, Bipolar Disorder
- Keywords
- Depression, Major Depressive Disorder, Bipolar Disorder, Mania, Hypomania, EEG, MRI, Reward
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 270 participants (actual)
- Lead sponsor
- Mclean HospitalUniversity, hospital or other
- Study start
- Oct 2013
- Primary completion
- Jan 2018 (actual)
- Study completion
- Jan 2018 (actual)
- First posted
- 6 Nov 2013 (estimated)
- Results
- Posted 23 Apr 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study aims to investigate reward learning across the mood disorder spectrum and to investigate the predictive validity of reward learning for subsequent symptom severity.
Detailed description
The study involves five sessions. In the first session, participants will play a computer task. In the second session, participants will go through a clinical interview and will have an EEG recording while playing another computer task. In the third session, participants will undergo an fMRI scan while playing another computer task. All tasks assess reward learning. At three and six months after the final session, participants will come back for a follow-up interview session during which a clinician will assess symptom severity. There will be no intervention in this study.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mood disorder patients | – | –Patients with depressive and/or manic or hypomanic symptoms |
| Healthy controls | – | –Participants with no lifetime history of psychiatric illness |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- We are studying a population with depressive and/or manic or hypomanic symptoms, as well as healthy controls.
Key inclusion criteria (8 listed)
- Written informed consent
- Right-handed
- (For mood disorder group only) Stable medication over the past 8 weeks OR absence of any psychotropic medications for at least 2 weeks (for follow-up analyses testing effects in medication-free patients):
Key exclusion criteria (10 listed)
- Suicidal ideation where outpatient treatment is determined unsafe by the study clinician
- Pregnant women or women of childbearing potential who 1) have not completed a negative urine pregnancy test prior to the MRI scan and/or 2) are seeking to become pregnant or believe that they may be pregnant
- Serious/unstable medical illness (e.g., cardiovascular, renal, endocrine, neurologic disease)
- Clinical or laboratory evidence of hypothyroidism
- History of seizure disorder, history or current diagnosis of dementia, score < 26 on the MMSE at screening
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Change in Response Bias
Time frame: Administered during the first session.
The Probabilistic Reward Task (PRT) is a behavioral task that measures an individual's ability to learn to choose a more rewarding outcome versus a less rewarding one (Response Bias). The response bias score is a ratio of the number of times a participant correctly chooses the high reward stimulus (the "rich" stimulus) versus the low reward stimulus (the "lean" stimulus). Response bias scores range between -1 and +1. A higher Response Bias score indicates a stronger bias toward the rich stimulus, and a negative Response Bias indicates a stronger bias toward the lean stimulus. The Change-in-Response-Bias is calculated by subtracting Response Bias in block 1 (trials 0-100) of the task from Response Bias in block 3 (trials 201-300) of the task. This metric represents the degree to which an individual is able to update behavior as a function of the asymmetrical reinforcement schedule.
Mean Accuracy on Gain Trials During an Instrumental Learning Task
Time frame: Administered in session 3 during 1.5 hour MR scan
The instrumental learning task requires participants to choose between two abstract symbols. Each symbol in the pair is associated with an 80% or 20% probability of a given outcome (gain: win $1 or $0; loss: lose $1 or $0; neutral: view a gray square or see the word 'nothing'). The task consists of three blocks. Behavioral performance focuses on the number of times the participant chose the symbol that was associated more frequently associated with the more desirable outcome. A participant scores 1 if they choose correctly, and 0 if they choose in correctly, and correct choices across all three blocks are added and converted to a percentage relative to the total number of trials in that condition (i.e., gain, loss, or neutral). This study focused on percent of accuracy responses in the gain condition.
1 secondary outcome
Symptom Severity at 6 Month Follow-up
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37841877Pizzagalli D, Whitton A, Treadway M, Rutherford A, Kumar P, Ironside M, Kaiser R, Ren B, Dan R. Brain-based graph-theoretical predictive modeling to map the trajectory of transdiagnostic symptoms of anhedonia, impulsivity, and hypomania from the human functional connectome. Res Sq [Preprint]. 2023 Sep 28:rs.3.rs-3168186. doi: 10.21203/rs.3.rs-3168186/v1.
- Derived from this study: PubMed 37402852Whitton AE, Kumar P, Treadway MT, Rutherford AV, Ironside ML, Foti D, Fitzmaurice G, Du F, Pizzagalli DA. Distinct profiles of anhedonia and reward processing and their prospective associations with quality of life among individuals with mood disorders. Mol Psychiatry. 2023 Dec;28(12):5272-5281. doi: 10.1038/s41380-023-02165-1. Epub 2023 Jul 4.
- Individual participant dataSharing planned: Undecided
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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.
Diego A Pizzagalli, Ph.D. principal investigator
Mclean Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Major Depressive Disorder and Bipolar Disorder, run by Mclean Hospital at 1 site in United States.
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 8 inclusion and 10 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: finished, as of the sponsor's last update on 4 Aug 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 United States. 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?
Yes. Results are posted in the registry (first posted 23 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Response Bias (time frame: Administered during the first session.). The study lists 2 primary outcomes in all. 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 NCT01976975, which also lists 2 linked publications.
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 4 Aug 2021.