Major Depressive DisorderPhase 4RAISENCT04276259

Rapid Antidepressant Improvement Secondary to Excitatory Brain Responses

A Phase 4 study testing Buprenorphine, Naltrexone and Theta burst stimulation (TBS) of the ventromedial prefrontal cortex. in people with Major Depressive Disorder and Depression, run by Marta Peciña, MD PhD at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

The central goal of this application is to demonstrate the causal contribution of reward learning signals (expected values and reward prediction errors [RPE]) to antidepressant responses (Aim1) by experimentally manipulating expected values using transcranial magnetic stimulation (TMS) targeting the vmPFC (Aim 2) and… Read more about this study

Who is it for?: Ages 18 to 55 years
Conditions the study is for: Major Depressive Disorder, Depression
What is being tested?: Buprenorphine, Naltrexone and Theta burst stimulation (TBS) of the ventromedial prefrontal cortex.
Type of treatment: Pill or oral medicine, Injection or infusion, Medical device
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 120 participants
Where: 1 siteUnited States
Study dates: 19 Oct 2020to 31 Mar 2026
Phase: Phase 4
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 18 to 55 years
All sexes
No healthy volunteers
Adult

Who may be able to join

Adults, age 18-55 years; fluent in English;
Written informed consent obtained;
Depressive symptoms with or without certain anxiety disorders (e.g., generalized anxiety, panic, agoraphobia, social phobia, and specific phobia);
No more than one failed antidepressant trial of adequate dose and duration, as defined by the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (MGH-ATRQ);
Participants can have previous history of antidepressant treatment but will need to be antidepressant medication-free for at least 21 days prior to the collection of imaging data (five weeks for fluoxetine).

Who cannot join

Pregnant or breastfeeding or plan to become pregnant over the duration of the study;
History (lifetime) of psychotic depressive, schizophrenic, bipolar (I, II, or NOS), schizoaffective, or other Axis I psychotic disorders;
Meeting M.I.N.I. criteria for substance dependence in the last 6 months, except for nicotine, or substance abuse in the last 2 months;
Requiring immediate hospitalization for psychiatric disorder or have an unstable general medical condition (GMC) that will likely require hospitalization or to be deemed terminal (life expectancy < 6 months after study entry);
Having epilepsy or other conditions requiring an anticonvulsant;
Receiving vagus nerve stimulation, electroconvulsive therapy, or repetitive Transcranial Magnetic Stimulation during the current episode.

Show all 18Show fewer

Currently taking any psychiatric medication or other potential augmenting agents (e.g., T3 in the absence of thyroid disease, lithium, buspirone); Taking thyroid medication for hypothyroidism may be included only if they have been stable on the thyroid medication for 3 months;
Receiving therapy that is depression specific, such as Cognitive Behavioral Therapy or Interpersonal Psychotherapy of Depression (participants can participate if they are receiving psychotherapy that is not targeting the symptoms of depression, such as supportive therapy, marital therapy);
Currently actively suicidal or considered a high suicide risk;
Patients are receiving opioid analgesics.
Patients are currently dependent on opioids.
Patients are in acute opioid withdrawal.
Any individual who has failed the naloxone challenge test or who has a positive urine screen for opioids.
Any individual with a history of sensitivity to buprenorphine or naltrexone.
Currently enrolled in another study, and participation in that study contraindicates participation in this study;
Any reason not listed herein yet, determined by the site PI and research staff that makes participation in the study hazardous.
Having any contraindication for the performance of TMS, such as the presence of a neurologic disorder or medication therapy known to alter seizure threshold (e.g., stroke, aneurysm, brain surgery, structural brain lesion, brain injury, frequent/severe headaches), recurrent seizures or epilepsy in participant or family history of hereditary epilepsy, pregnancy, metallic implants in body or other devices that may be affected by magnetic field or significant heart disease or cerebrovascular disease.
Having any contraindication for the performance of an MRI, such as the presence of metal implants or foreign metallic objects (e.g., braces or extensive dental work), severe claustrophobia, or inability to tolerate the scanning procedures.

Trial locations and contacts

1 site in 1 country.

United States1 site

Bellefield Tower
Pittsburgh, Pennsylvania, 15213

Other trials in United States

About this study

Official title: Neurocomputational Mechanisms of Mood Improvement

Read the detailed description

The central goal of this study is to demonstrate the causal contribution of reward learning signals (expected values and RPEs) to antidepressant responses (Aim1) by experimentally manipulating expected values using transcranial magnetic stimulation (TMS) targeting the vmPFC (Aim 2) and μ-opioid striatal RPE signal using pharmacological approaches (Aim 3). In a 3x3 factorial double-blind trial, the investigators will randomize 120 unmedicated major depressive disorder (MDD) adults (18-55 years) to one of three between-subject opioid conditions: the μ-opioid agonist buprenorphine (n=40), the μ-opioid antagonist naltrexone (n=40), or the inert pill (n=40). Within each arm, individuals will be assigned to receive three within-subject counterbalanced sessions of TMS targeting the vmPFC-intermittent TBS (iTBS) expected to potentiate the vmPFC, continuous TBS (cTBS) expected to de-potentiate the vmPFC, and sham TBS (sTBS). These experimental manipulations will be used to modulate trial-by-trial reward learning signals and related brain activity during the Antidepressant fMRI Task. Understanding the mechanisms underlying antidepressant responses is essential to identify novel therapeutic targets for depression.

Conditions: Major Depressive Disorder, Depression
Being tested: Buprenorphine, Naltrexone, Oral Placebo, IM Placebo, Theta burst stimulation (TBS) of the ventromedial prefrontal cortex.
Medical subject headings: Depressive Disorder, Major, Depression

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BuprenorphineDrug
Buprenorphine is a μ-opioid partial agonist and kappa-opioid antagonist that is used to treat moderate to severe pain and opioid dependence. The intramuscular administered opioid agonist which will be used to modulate reward learning signals to understand placebo effects in patients with depression. In the buprenorphine condition, participants will receive one IM injection of 0.3mg/1ML buprenorphine hydrochloride (Buprenex®. Richmond, VA: Reckitt Benckiser Pharmaceuticals Inc.; 2006) (onset of action: ≥15 minutes; peak effect: ~1 hour; duration: ~6 hours) and an oral placebo tablet.
NaltrexoneDrug
Naltrexone is thought to strongly block μ-opioid receptors. Oral (pill) opioid antagonist which will be used to modulate reward learning signals to understand placebo effects in participants with depression. In the naltrexone condition, participants will receive one tablet of 50mg Naltrexone hydrochloride (ReVia®. Toronto, ON: Teva Canada Limited; 2015) (onset of action: ≥15 minutes; peak effect: ~1 hour; duration: ~24 hours) and a saline IM injection.
Oral PlaceboDrug
Oral placebo: to match the oral naltrexone.
IM PlaceboDrug
IM saline placebo: to match the i.v. buprenorphine.
Theta burst stimulation (TBS) of the ventromedial prefrontal cortex.Device
Also called sham (s), continuous (c) and intermittent (i).
Participants will receive two blocks of each TBS form. During the first block, stimulation intensity will be gradually escalated in 5% increments (from 80% to 110% rMT) in order to enhance tolerability. In all conditions, the investigators will apply 600 pulses of theta burst at 110% RMT. Each block of iTBS will consist of 20 trains, each lasting 2s with intertrain intervals of 8s, for a total of 192s. Each block of cTBS will consist of one continuous train of 40s. The sTBS will make use of two surface electrodes placed on the scalp.

Study groups in NCT04276259
Study group	Role	What they receive
Buprenorphine Injection + Oral Placebo Pill	Experimental	Buprenorphine is a μ-opioid partial agonist and kappa-opioid antagonist that is used to treat moderate to severe pain and opioid dependence. The intramuscular administered opioid agonist which will be used to modulate reward learning signals to understand placebo effects in patients with depression. In the buprenorphine condition, participants will receive one IM injection of 0.3mg/1ML buprenorphine hydrochloride (Buprenex®. Richmond, VA: Reckitt Benckiser Pharmaceuticals Inc.; 2006) (onset of action: ≥15 minutes; peak effect: ~1 hour; duration: ~6 hours) and an oral placebo tablet. Receives: Drug: Buprenorphine; Drug: Oral Placebo; Device: Theta burst stimulation (TBS) of the ventromedial prefrontal cortex.
Naltrexone Oral Tablet + Intramuscular Saline Injection	Experimental	Naltrexone is thought to strongly block μ-opioid receptors. Oral (pill) opioid antagonist which will be used to modulate reward learning signals to understand placebo effects in participants with depression. In the naltrexone condition, participants will receive one tablet of 50mg Naltrexone hydrochloride (ReVia®. Toronto, ON: Teva Canada Limited; 2015) (onset of action: ≥15 minutes; peak effect: ~1 hour; duration: ~24 hours) and a saline IM injection. Receives: Drug: Naltrexone; Drug: IM Placebo; Device: Theta burst stimulation (TBS) of the ventromedial prefrontal cortex.
Oral Placebo Pill + Intramuscular Saline Injection	Experimental	Inert pill and saline injection that have no inherent power to produce an effect. In the inert pill condition, participants will receive one IM arm injection of saline (1ML) and an oral placebo tablet. Receives: Drug: Oral Placebo; Drug: IM Placebo; Device: Theta burst stimulation (TBS) of the ventromedial prefrontal cortex.

What is being measured

The primary outcome is the main question the study is designed to answer.

BOLD Responses in the vmPFC-VS circuit
Changes in blood oxygenation level-dependent (BOLD) signal during the Antidepressant fMRI Task.
Measured: Approximately at day 7, 14, 21.
TBS Effects of BOLD Response
Changes in BOLD signal during the Antidepressant fMRI Task between iTBS vs. sTBS, and cTBS vs. sTBS.
Measured: Approximately at day 7, 14, 21.
Opioid Modulation Effects on BOLD Responses in the vmPFC-VS circuit
Changes in BOLD signal during the Antidepressant fMRI Task between Buprenorphine vs. inert pill, and Naltrexone vs. inert pill.
Measured: Approximately at day 7, 14, 21.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

19 Oct 202031 Mar 2026

First posted19 Feb 2020
Study start19 Oct 2020
Primary completion31 Mar 2026
Study completion31 Mar 2026

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
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: Interventional
Phase: Phase 4
Primary purpose: Other
Allocation: Randomised
Intervention model: Factorial
Model description: This is a mechanistic trial.
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 120 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04276259
Sponsor's protocol ID: STUDY19050307
Other IDs: 1R01MH122548-01
Acronym: RAISE
Status last verified: Feb 2026
First submitted: 6 Feb 2020
Last updated: 31 Jul 2026
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: Yes
Individual data sharing: Yes: Consistent with NIMH Data Archive (NDA) policies, the investigators will obtain relevant GUIDs and experiment IDs in order to upload all relevant data biannually. The investigators will use the Validation and Upload Tool for CSV files from behavior during the fMRI experiment, and NIfTI-formatted images for imaging. The investigators will upload study data cumulatively every 6 months per NDA guidelines, with the exception of imaging data, which are will be uploaded in installments. The final research data will not contain any identifiable information and will be deposited in the Research Domain Criteria Database (RDoCdb) repository in the NDA prior to the acceptance for publication of the main findings from the final dataset. Documentation and code for computational models developed as part of this project will be shared upon request.

Publications

Snyder I, Handoko K, Neppach A, Badhan G, Karim HT, Price RB, Ferrarelli F, Dombrovski AY, Pecina M. Intermittent Theta Burst Stimulation of the Dorsomedial PFC and Expectancy-Driven Placebo Mood Effects: A Randomized Clinical Trial. JAMA Psychiatry. 2026 Jul 1;83(7):704-713. doi: 10.1001/jamapsychiatry.2026.0647.
PubMed 42090145
Pecina M, Dombrovski AY, Price R, Karim HT. Understanding the Neurocomputational Mechanisms of Antidepressant Placebo Effects. J Psychiatr Brain Sci. 2021;6:e210001. doi: 10.20900/jpbs.20210001. Epub 2021 Feb 15.
PubMed 33732892

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruiting
Preventive and Personalized Digital Emotion Regulation Skills Intervention to Reduce Depression and Anxiety in Youths With Adverse Childhood Experiences
Adverse Childhood Experience, Depression / Major Depressive Disorder
RecruitingPhase 4
Biomarker-Guided Antidepressant Selection
Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD)
Recruiting
Targeting Network Dysfunction in Apathy of Late-life Depression Using Digital Therapeutics
Major Depressive Disorder, Apathy
RecruitingObservational study
Student Precarity and Psychiatry
Depressive Disorder, Major, Generalized Anxiety Disorder
Not yet recruiting
Acute Intermittent Hypoxia Therapy for Depression
Major Depressive Disorder (MDD)

All Major Depressive Disorder trials

Study at a glance

From the registry record, last updated by the sponsor on 31 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Neurocomputational Mechanisms of Mood Improvement
ClinicalTrials.gov ID: NCT04276259
Acronym / sponsor ID: RAISE / STUDY19050307
Conditions: Major Depressive Disorder, Depression
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 120 participants (actual)
Lead sponsor: Marta Peciña, MD PhDUniversity, hospital or other
Collaborators: National Institute of Mental Health (NIMH)
Study start: 19 Oct 2020 (actual)
Primary completion: 31 Mar 2026 (actual)
Study completion: 31 Mar 2026 (actual)
First posted: 19 Feb 2020 (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.

Detailed description

Study design

Primary purpose: Other
Allocation: Randomised
Intervention model: Factorial
Masking: Double blind (participant, investigator)
Number of arms: 3
Model description: This is a mechanistic trial.

Arm	Type	Receives
Buprenorphine Injection + Oral Placebo Pill	Experimental	Drug: Buprenorphine, Drug: Oral Placebo, Device: Theta burst stimulation (TBS) of the ventromedial prefrontal cortex.Buprenorphine is a μ-opioid partial agonist and kappa-opioid antagonist that is used to treat moderate to severe pain and opioid dependence. The intramuscular administered opioid agonist which will be used to modulate reward learning signals to understand placebo effects in patients with depression. In the buprenorphine condition, participants will receive one IM injection of 0.3mg/1ML buprenorphine hydrochloride (Buprenex®. Richmond, VA: Reckitt Benckiser Pharmaceuticals Inc.; 2006) (onset of action: ≥15 minutes; peak effect: ~1 hour; duration: ~6 hours) and an oral placebo tablet.
Naltrexone Oral Tablet + Intramuscular Saline Injection	Experimental	Drug: Naltrexone, Drug: IM Placebo, Device: Theta burst stimulation (TBS) of the ventromedial prefrontal cortex.Naltrexone is thought to strongly block μ-opioid receptors. Oral (pill) opioid antagonist which will be used to modulate reward learning signals to understand placebo effects in participants with depression. In the naltrexone condition, participants will receive one tablet of 50mg Naltrexone hydrochloride (ReVia®. Toronto, ON: Teva Canada Limited; 2015) (onset of action: ≥15 minutes; peak effect: ~1 hour; duration: ~24 hours) and a saline IM injection.
Oral Placebo Pill + Intramuscular Saline Injection	Experimental	Drug: Oral Placebo, Drug: IM Placebo, Device: Theta burst stimulation (TBS) of the ventromedial prefrontal cortex.Inert pill and saline injection that have no inherent power to produce an effect. In the inert pill condition, participants will receive one IM arm injection of saline (1ML) and an oral placebo tablet.

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (5 listed)

Adults, age 18-55 years; fluent in English;
Written informed consent obtained;
Depressive symptoms with or without certain anxiety disorders (e.g., generalized anxiety, panic, agoraphobia, social phobia, and specific phobia);
No more than one failed antidepressant trial of adequate dose and duration, as defined by the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (MGH-ATRQ);
Participants can have previous history of antidepressant treatment but will need to be antidepressant medication-free for at least 21 days prior to the collection of imaging data (five weeks for fluoxetine).

Key exclusion criteria (18 listed)

Pregnant or breastfeeding or plan to become pregnant over the duration of the study;
History (lifetime) of psychotic depressive, schizophrenic, bipolar (I, II, or NOS), schizoaffective, or other Axis I psychotic disorders;
Meeting M.I.N.I. criteria for substance dependence in the last 6 months, except for nicotine, or substance abuse in the last 2 months;
Requiring immediate hospitalization for psychiatric disorder or have an unstable general medical condition (GMC) that will likely require hospitalization or to be deemed terminal (life expectancy < 6 months after study entry);
Having epilepsy or other conditions requiring an anticonvulsant;

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
BuprenorphineBuprenorphine is a μ-opioid partial agonist and kappa-opioid antagonist that is used to treat moderate to severe pain and opioid dependence. The intramuscular administered opioid agonist which will be used to modulate reward learning signals to understand placebo effects in patients with depression. In the buprenorphine condition, participants will receive one IM injection of 0.3mg/1ML buprenorphine hydrochloride (Buprenex®. Richmond, VA: Reckitt Benckiser Pharmaceuticals Inc.; 2006) (onset of action: ≥15 minutes; peak effect: ~1 hour; duration: ~6 hours) and an oral placebo tablet.	Drug	Buprenorphine Injection + Oral Placebo Pill
NaltrexoneNaltrexone is thought to strongly block μ-opioid receptors. Oral (pill) opioid antagonist which will be used to modulate reward learning signals to understand placebo effects in participants with depression. In the naltrexone condition, participants will receive one tablet of 50mg Naltrexone hydrochloride (ReVia®. Toronto, ON: Teva Canada Limited; 2015) (onset of action: ≥15 minutes; peak effect: ~1 hour; duration: ~24 hours) and a saline IM injection.	Drug	Naltrexone Oral Tablet + Intramuscular Saline Injection
Oral PlaceboOral placebo: to match the oral naltrexone.	Drug	Buprenorphine Injection + Oral Placebo Pill, Oral Placebo Pill + Intramuscular Saline Injection
IM PlaceboIM saline placebo: to match the i.v. buprenorphine.	Drug	Naltrexone Oral Tablet + Intramuscular Saline Injection, Oral Placebo Pill + Intramuscular Saline Injection
Theta burst stimulation (TBS) of the ventromedial prefrontal cortex.Also: sham (s), continuous (c) and intermittent (i).Participants will receive two blocks of each TBS form. During the first block, stimulation intensity will be gradually escalated in 5% increments (from 80% to 110% rMT) in order to enhance tolerability. In all conditions, the investigators will apply 600 pulses of theta burst at 110% RMT. Each block of iTBS will consist of 20 trains, each lasting 2s with intertrain intervals of 8s, for a total of 192s. Each block of cTBS will consist of one continuous train of 40s. The sTBS will make use of two surface electrodes placed on the scalp.	Device	Buprenorphine Injection + Oral Placebo Pill, Naltrexone Oral Tablet + Intramuscular Saline Injection, Oral Placebo Pill + Intramuscular Saline Injection

Primary outcome

BOLD Responses in the vmPFC-VS circuit
Time frame: Approximately at day 7, 14, 21.
Changes in blood oxygenation level-dependent (BOLD) signal during the Antidepressant fMRI Task.
TBS Effects of BOLD Response
Time frame: Approximately at day 7, 14, 21.
Changes in BOLD signal during the Antidepressant fMRI Task between iTBS vs. sTBS, and cTBS vs. sTBS.
Opioid Modulation Effects on BOLD Responses in the vmPFC-VS circuit
Time frame: Approximately at day 7, 14, 21.
Changes in BOLD signal during the Antidepressant fMRI Task between Buprenorphine vs. inert pill, and Naltrexone vs. inert pill.

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2026.
Derived from this study: PubMed 42090145Snyder I, Handoko K, Neppach A, Badhan G, Karim HT, Price RB, Ferrarelli F, Dombrovski AY, Pecina M. Intermittent Theta Burst Stimulation of the Dorsomedial PFC and Expectancy-Driven Placebo Mood Effects: A Randomized Clinical Trial. JAMA Psychiatry. 2026 Jul 1;83(7):704-713. doi: 10.1001/jamapsychiatry.2026.0647.
Derived from this study: PubMed 33732892Pecina M, Dombrovski AY, Price R, Karim HT. Understanding the Neurocomputational Mechanisms of Antidepressant Placebo Effects. J Psychiatr Brain Sci. 2021;6:e210001. doi: 10.20900/jpbs.20210001. Epub 2021 Feb 15.
Individual participant dataSharing planned: Yes. Consistent with NIMH Data Archive (NDA) policies, the investigators will obtain relevant GUIDs and experiment IDs in order to upload all relevant data biannually. The investigators will use the Validation and Upload Tool for CSV files from behavior during the fMRI experiment, and NIfTI-formatted images for imaging. The investigators will upload study data cumulatively every 6 months per NDA guidelines, with the exception of imaging data, which are will be uploaded in installments. The final research data will not contain any identifiable information and will be deposited in the Research Domain Criteria Database (RDoCdb) repository in the NDA prior to the acceptance for publication of the main findings from the final dataset. Documentation and code for computational models developed as part of this project will be shared upon request.

Related trials for Major Depressive Disorder

Not yet recruiting
Preventive and Personalized Digital Emotion Regulation Skills Intervention to Reduce Depression and Anxiety in Youths With Adverse Childhood Experiences
Adverse Childhood Experience, Depression / Major Depressive Disorder
RecruitingPhase 4
Biomarker-Guided Antidepressant Selection
Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD)
Recruiting
Targeting Network Dysfunction in Apathy of Late-life Depression Using Digital Therapeutics
Major Depressive Disorder, Apathy
RecruitingObservational study
Student Precarity and Psychiatry
Depressive Disorder, Major, Generalized Anxiety Disorder
Not yet recruiting
Acute Intermittent Hypoxia Therapy for Depression
Major Depressive Disorder (MDD)

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.

Marta Peciña, MD, PhD principal investigator

University of Pittsburgh

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 5 inclusion and 18 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 31 Jul 2026. 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.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

BOLD Responses in the vmPFC-VS circuit (time frame: Approximately at day 7, 14, 21.). The study lists 3 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 NCT04276259, 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 31 Jul 2026.