Major Depressive DisorderNCT04487730
Social Reward and Its Effect on Brain Functions in Psychotherapies for Mid- and Late-Life Depression
A study testing "Engage & Connect" Psychotherapy and Symptom Review and Psychoeducation (SRP) in people with Major Depressive Disorder, run by Weill Medical College of Cornell University at 1 site in United States.
Trial summary
Abnormalities in the Positive Valence System (PVS) are associated with depressive symptoms and reduced behavioral activation in mid- and late-life. This study will investigate the engagement of the PVS during exposure to social rewards, part of a novel streamlined psychotherapy for mid- and late-life depression. Read more about this study
- Who is it for?
- Ages 50 to 85 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- "Engage & Connect" Psychotherapy and Symptom Review and Psychoeducation (SRP)
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Oct 2020to 19 Aug 2024
- Phase
- Interventional
- 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 50 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ages aged 50-85 [stratified so that 50% are older than 65]
- Diagnosis of unipolar major depressive disorder without psychotic features, determined by the SCID
- Montgomery-Åsberg Depression Rating Scale (MADRS) score ≥ 20.
- Mini Mental Status Exam (MMSE) ≤ 1 SD below the mean score for patient's age and education
- Off antidepressants or on a stable dose of an antidepressant for 8 weeks and do not intend to change the dose in the next 10 weeks.
- Capacity to provide written consent for research assessment and treatment.
Who cannot join
- Intent or plan to attempt suicide in the near future.
- History or presence of psychiatric diagnoses other than major depressive disorder without psychotic features, generalized anxiety disorder, or specific phobia.
- Use of psychotropic drugs or cholinesterase inhibitors other than use of ≤ 0.5 mg of lorazepam daily up to seven times per week.
- Neurological disorders (dementias, history of stroke, multiple sclerosis, Parkinson's disease, epilepsy, etc.); cardiac, renal, or respiratory failure; severe chronic obstructive pulmonary disease; metastatic cancer; or debilitated states or less common medical illnesses that may either influence brain systems of interest or ability to participate in the study. Dr. Alexopoulos or another research psychiatrist will review any medical illnesses that does not appear in the list above and determine whether it interferes with the study of positive valence system functions in depression.
- Contraindications to MRI scanning including cardiac pacemaker, heart valve replacement, vascular stent, insulin pump, cochlear implant, any other metallic biomedical implant contraindicating to MRI, and claustrophobia.
Trial locations and contacts
1 site in 1 country.
About this study
Abnormalities in the Positive Valence System (PVS) are associated with depressive symptoms and reduced behavioral activation in mid- and late-life. This study will investigate the engagement of the PVS during exposure to social rewards, part of a novel streamlined psychotherapy for mid- and late-life depression. Use of computational modeling will enable identification of neuroimaging and behavioral profiles associated with greater treatment response, and may guide future personalization of psychotherapy.
- Conditions
- Major Depressive Disorder
- Being tested
- "Engage & Connect" Psychotherapy, Symptom Review and Psychoeducation (SRP)
- Keywords
- Late Life Depression, Psychotherapy, Mechanisms of Action, Positive Valence System, Social Reward
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
"Engage & Connect" PsychotherapyBehavioural
9-weeks of weekly psychotherapy sessions focused on social reward exposure
Symptom Review and Psychoeducation (SRP)Behavioural
9-weeks of weekly psychotherapy sessions focused on symptom review and psychoeducation about depression and aging
| Study group | Role | What they receive |
|---|---|---|
| "Engage & Connect" Psychotherapy | Experimental | "Engage \& Connect", a modified adapted version of "Engage". Its principal intervention is "social reward exposure" - facilitating engagement in rewarding and meaningful social activities with significant others. In "Engage-S" therapy, individuals with depression work with a therapist to develop "action plans" to pursue rewarding social activities of their choice. Receives: Behavioral: "Engage & Connect" Psychotherapy |
| Symptom Review and Psychoeducation (SRP) | Active comparator | In this intervention, the therapist will review the participant's symptoms and provide literature-based clinical explanations and clarifications about the symptoms, the course, and the causes of depression. In SRP, the therapist reviews the depressed individual's symptoms, and level of information on depression, identifies misconceptions, and guides selection of educational material which could benefit the patient. Receives: Behavioral: Symptom Review and Psychoeducation (SRP) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Resting State fMRI Connectivity of the Positive Valence System
Calculated from fMRI scan. Validation of target engagement (resting state functional connectivity (rsFC) within the right hemisphere orbital prefrontal cortex (OFC), specifically between the lateral and medial regions of the OFC).
Measured: Baseline, Mid-treatment (Week 5) and Post Treatment (Week 9)
Secondary outcomes (2)
Change in Montgomery Asberg Depression Rating Scale (MADRS)
10-item Clinician rated measure of depression severity. Scores range from 0 (no depression) to 60 (severe depression).
Measured: Baseline, Mid-treatment (Week 5) and Post Treatment (Week 9)
Change in Behavioral Activation for Depression Scale (BADS)
25-item measure self-report measure of behavioral activation. Scores range from 0 (very low behavioral activation) to 150 (high behavioral activation).
Measured: Baseline, Mid-treatment (Week 5) and Post Treatment (Week 9)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2020
- Study start15 Oct 2020
- Primary completion13 Aug 2024
- Study completion19 Aug 2024
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.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Weill Medical College of Cornell UniversityThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a randomized controlled trial. Participants will be randomly assigned to 9-weeks of either "Engage-S" Psychotherapy or "Symptom Review and Psychoeducation" (SRP) Psychotherapy
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- Weill Medical College of Cornell University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- Nili Solomonov, PhD, Principal investigator, Weill Medical College of Cornell University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04487730
- Sponsor's protocol ID
- 20-04021860
- Other IDs
- K23MH123864-01
- Status last verified
- May 2025
- First submitted
- 23 Jul 2020
- Last updated
- 3 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in publications, after de-identification, as well as study protocol, treatment manuals, statistical analysis plan and informed consent. We will also share our fMRI tasks and analytic code by request with all interested researchers.
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Social Reward and Its Effect on Brain Functions in Psychotherapies for Mid- and Late-Life Depression
- ClinicalTrials.gov ID
- NCT04487730
- Acronym / sponsor ID
- 20-04021860
- Conditions
- Major Depressive Disorder
- Keywords
- Late Life Depression, Psychotherapy, Mechanisms of Action, Positive Valence System, Social Reward
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- Weill Medical College of Cornell UniversityUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 15 Oct 2020 (actual)
- Primary completion
- 13 Aug 2024 (actual)
- Study completion
- 19 Aug 2024 (actual)
- First posted
- 27 Jul 2020 (actual)
- Results
- Posted 3 Jun 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Abnormalities in the Positive Valence System (PVS) are associated with depressive symptoms and reduced behavioral activation in mid- and late-life. This study will investigate the engagement of the PVS during exposure to social rewards, part of a novel streamlined psychotherapy for mid- and late-life depression. Use of computational modeling will enable identification of neuroimaging and behavioral profiles associated with greater treatment response, and may guide future personalization of psychotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- This is a randomized controlled trial. Participants will be randomly assigned to 9-weeks of either "Engage-S" Psychotherapy or "Symptom Review and Psychoeducation" (SRP) Psychotherapy
| Arm | Type | Receives |
|---|---|---|
| "Engage & Connect" Psychotherapy | Experimental | Behavioral: "Engage & Connect" Psychotherapy"Engage \& Connect", a modified adapted version of "Engage". Its principal intervention is "social reward exposure" - facilitating engagement in rewarding and meaningful social activities with significant others. In "Engage-S" therapy, individuals with depression work with a therapist to develop "action plans" to pursue rewarding social activities of their choice. |
| Symptom Review and Psychoeducation (SRP) | Active comparator | Behavioral: Symptom Review and Psychoeducation (SRP)In this intervention, the therapist will review the participant's symptoms and provide literature-based clinical explanations and clarifications about the symptoms, the course, and the causes of depression. In SRP, the therapist reviews the depressed individual's symptoms, and level of information on depression, identifies misconceptions, and guides selection of educational material which could benefit the patient. |
Who may qualify
- Ages
- 50 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Ages aged 50-85 [stratified so that 50% are older than 65]
- Diagnosis of unipolar major depressive disorder without psychotic features, determined by the SCID
- Montgomery-Åsberg Depression Rating Scale (MADRS) score ≥ 20.
- Mini Mental Status Exam (MMSE) ≤ 1 SD below the mean score for patient's age and education
- Off antidepressants or on a stable dose of an antidepressant for 8 weeks and do not intend to change the dose in the next 10 weeks.
Key exclusion criteria (5 listed)
- Intent or plan to attempt suicide in the near future.
- History or presence of psychiatric diagnoses other than major depressive disorder without psychotic features, generalized anxiety disorder, or specific phobia.
- Use of psychotropic drugs or cholinesterase inhibitors other than use of ≤ 0.5 mg of lorazepam daily up to seven times per week.
- Neurological disorders (dementias, history of stroke, multiple sclerosis, Parkinson's disease, epilepsy, etc.); cardiac, renal, or respiratory failure; severe chronic obstructive pulmonary disease; metastatic cancer; or debilitated states or less common medical illnesses that may either influence brain systems of interest or ability to participate in the study. Dr. Alexopoulos or another research psychiatrist will review any medical illnesses that does not appear in the list above and determine whether it interferes with the study of positive valence system functions in depression.
- Contraindications to MRI scanning including cardiac pacemaker, heart valve replacement, vascular stent, insulin pump, cochlear implant, any other metallic biomedical implant contraindicating to MRI, and claustrophobia.
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 |
|---|---|---|
| "Engage & Connect" Psychotherapy9-weeks of weekly psychotherapy sessions focused on social reward exposure | Behavioural | "Engage & Connect" Psychotherapy |
| Symptom Review and Psychoeducation (SRP)9-weeks of weekly psychotherapy sessions focused on symptom review and psychoeducation about depression and aging | Behavioural | Symptom Review and Psychoeducation (SRP) |
Primary outcome
Change in Resting State fMRI Connectivity of the Positive Valence System
Time frame: Baseline, Mid-treatment (Week 5) and Post Treatment (Week 9)
Calculated from fMRI scan. Validation of target engagement (resting state functional connectivity (rsFC) within the right hemisphere orbital prefrontal cortex (OFC), specifically between the lateral and medial regions of the OFC).
2 secondary outcomes
Change in Montgomery Asberg Depression Rating Scale (MADRS)
Time frame: Baseline, Mid-treatment (Week 5) and Post Treatment (Week 9)
Change in Behavioral Activation for Depression Scale (BADS)
Time frame: Baseline, Mid-treatment (Week 5) and Post Treatment (Week 9)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in publications, after de-identification, as well as study protocol, treatment manuals, statistical analysis plan and informed consent. We will also share our fMRI tasks and analytic code by request with all interested researchers.
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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.
Nili Solomonov, PhD principal investigator
Weill Medical College of Cornell University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing "Engage & Connect" Psychotherapy and Symptom Review and Psychoeducation (SRP) in people with Major Depressive Disorder, run by Weill Medical College of Cornell University 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 6 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: finished, as of the sponsor's last update on 3 Jun 2025. 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 3 Jun 2025). 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 Resting State fMRI Connectivity of the Positive Valence System (time frame: Baseline, Mid-treatment (Week 5) and Post Treatment (Week 9)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 Jun 2025.