Depressive Disorder, MajorPhase 2NCT05232032
Pharmaco-Neuroimaging Studies of Approach/Avoidance Behaviors and Post-Mortem Studies: Pharmacological Manipulation
A Phase 2 study testing Nociceptin Receptor Antagonist and Aversive stimuli in people with Depressive Disorder, Major and Anxiety Disorder, run by Mclean Hospital at 1 site in United States.
Trial summary
The study will investigate whether a nociceptin receptor antagonist will normalize neural and behavioral processes of approach/avoidance decision-making in unmedicated individuals with major depressive disorder (MDD) and anxiety disorders. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Depressive Disorder, Major, Anxiety Disorder
- What is being tested?
- Nociceptin Receptor Antagonist and Aversive stimuli
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 112 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Feb 2025to 31 Mar 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- DSM-5 diagnostic criteria for MDD, Generalized Anxiety Disorder, Social Phobia, Panic Disorder, Post Traumatic Stress (diagnosed using the SCID-5)
- Written informed consent
- For MDD subjects, a baseline Hamilton Depression Rating Scale score > 16 (17-item version)
- Right-handed
- Has a smartphone (iPhone or Android) (needed for Ecological Momentary Assessment)
- Absence of any psychotropic medications for at least 2 weeks (6 weeks for fluoxetine, 6 months for neuroleptics, 2 weeks for benzodiazepines, 2 weeks for any other antidepressants)
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- Absence of medical, neurological, and psychiatric illness (including alcohol and substance abuse), as assessed by subject history and a structured clinical interview (diagnosed using the SCID-5)
- Written informed consent
- Right-handed
- Absence of any medications for at least 3 weeks
- Has a smartphone (iPhone or Android) (needed for Ecological Momentary Assessment)
Who cannot join
- Subjects with suicidal ideation where outpatient treatment is determined unsafe by the study clinician
- Pregnant women or women of childbearing potential who are not using a medically accepted means of contraception
- Serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic or hematologic disease
- History of seizure disorder
- History or current diagnosis of any of the following DSM-IV psychiatric illnesses: organic mental disorder, schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorders not otherwise specified, bipolar disorder, obsessive-compulsive disorder, patients with mood congruent or mood incongruent psychotic features, substance dependence, substance abuse within the last 12 months (with the exception of cocaine or stimulant abuse; which will lead to exclusion)
- History of cocaine or stimulant use (e.g., amphetamine, cocaine, methamphetamine)
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- History of use of dopaminergic drugs (including methylphenidate)
- History or current diagnosis of dementia
- Patients with mood congruent or mood incongruent psychotic features
- Current use of other psychotropic drugs
- Clinical or laboratory evidence of hypothyroidism
- Patients with a lifetime history of electroconvulsive therapy
- Failure to meet standard magnetic resonance imaging safety requirements
- Abnormal ECG and lab results
- History of seizure disorder or currently on anticonvulsants
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Mclean Hospital
Belmont, Massachusetts, 02478
Ethan Zhang, BA, 617-855-4434, ezhang24@mclean.harvard.edu
David Crowley, ALM, djcrowley@mclean.harvard.edu
About this study
Official title: Pharmaco-Neuroimaging Studies of Approach/Avoidance Behaviors and Post-Mortem Studies: Study 1.1. (Pharmacological Manipulation)
The study will investigate whether a nociceptin receptor antagonist will normalize neural and behavioral processes of approach/avoidance decision-making in unmedicated individuals with major depressive disorder (MDD) and anxiety disorders. More specifically, the study aims to investigate dysregulation within (1) corticostriatal-midbrain circuitry and (2) nociceptin/orphanin FQ peptide and the nociceptin receptor (NOPR).
- Conditions
- Depressive Disorder, Major, Anxiety Disorder
- Being tested
- Nociceptin Receptor Antagonist, Aversive stimuli
- Medical subject headings
- Depressive Disorder, Major, Anxiety Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nociceptin Receptor AntagonistDrug
Also called BTRX-246040
Participants in the experimental arms will receive 40 mg of the nociceptin receptor antagonist. Peak concentrations are achieved 2-4 hours post-administration.
Aversive stimuliDevice
As part of the approach/avoidance task, electrotactile stimulation will be used. The aversive stimulus is delivered in the form of a mild half-second stimulation to the ankle, calibrated to a subjective threshold that is uncomfortable but not painful. This stimulation is delivered by Digitimer DS8R Constant Current Stimulator (Digitimer North America, LLC. Ft. Lauderdale, FL). Its previous model, DS71, has been safely implemented in studies within Massachusetts General Hospital (Milad et al., 2013).
| Study group | Role | What they receive |
|---|---|---|
| Participants with MDD or an anxiety disorder receiving the nociceptin receptor antagonist | Experimental | After a diagnostic interview (determining the presence of MDD or an anxiety disorder) and collection of blood for Orphanin FQ/Nociceptin assays, participants will receive the nociceptin receptor antagonist. Participants will then complete an approach/avoidance task. Functional magnetic resonance imagining (fMRI) will begin 2 hours after the nociceptin receptor antagonist is administered. Receives: Drug: Nociceptin Receptor Antagonist; Device: Aversive stimuli |
| Participants with MDD or an anxiety disorder receiving the placebo | Placebo comparator | After a diagnostic interview (determining the presence of MDD or an anxiety disorder) and collection of blood for Orphanin FQ/Nociceptin assays, participants will receive the placebo. Participants will then complete an approach/avoidance task. fMRI will begin 2 hours after the placebo is administered. Receives: Device: Aversive stimuli |
| Healthy controls receiving the nociceptin receptor antagonist | Experimental | After a diagnostic interview (determining healthy control status) and collection of blood for Orphanin FQ/Nociceptin assays, participants will receive a nociceptin receptor antagonist. Participants will then complete an approach/avoidance task. fMRI will begin 2 hours after the nociceptin receptor antagonist is administered. Receives: Drug: Nociceptin Receptor Antagonist; Device: Aversive stimuli |
| Healthy controls receiving the placebo | Placebo comparator | After a diagnostic interview (determining healthy control status) and collection of blood for Orphanin FQ/Nociceptin assays, participants will receive the placebo. Participants will then complete an approach/avoidance task. fMRI will begin 2 hours after the placebo is administered. Receives: Device: Aversive stimuli |
What is being measured
The primary outcome is the main question the study is designed to answer.
Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (SCID-5)
Diagnostic assessment
Measured: Baseline
Magnetic Resonance Imagining
Both structural and functional brain images
Measured: Within 30 days of the clinical interview
Approach/Avoidance Task
A novel behavioral task assessing approach/avoidance decision-making
Measured: During the MRI scan
Orphanin FQ/Nociceptin assays (using blood samples)
Measure of Orphanin FQ/Nociceptin
Measured: On the day of the MRI scan
Secondary outcomes (10)
Beck Depression Inventory-II
21-item measure of depression severity; scores range from 0 to 63; higher scores indicate higher depression severity
Measured: Baseline, 6-month follow-up, 12-month follow-up
Hamilton Rating Scale for Depression
17-item measure of depression severity; scores range from 0 to 34; higher scores indicate higher depression severity
Measured: Baseline, 6-month follow-up, 12-month follow-up
Perceived Stress Scale
14-item measure of stress appraisal; scores range from 0 to 56; higher scores indicate higher perceived stress
Measured: Baseline, 6-month follow-up, 12-month follow-up
Snaith Hamilton Pleasure Scale
14-item measure of anhedonia; scores range from 14 to 56; higher scores indicate higher anhedonia
Measured: Baseline, 6-month follow-up, 12-month follow-up
Medical Outcome Survey- Short Form
36-item measure of physical and social functioning; score range from 36 to 149; higher scores indicate higher physical and social functioning
Measured: Baseline, 6-month follow-up, 12-month follow-up
Quality of Life Enjoyment and Satisfaction Questionnaire
16-item measure of satisfaction and enjoyment across domains (e.g., work, interpersonal); scores range from 16 to 80; higher scores indicate higher life enjoyment and satisfaction
Measured: Baseline, 6-month follow-up, 12-month follow-up
Temporal Experience of Pleasure Scale
24-item measure of anticipatory and consummatory pleasure; scores range from 24 to 144; higher scores indicate higher anticipatory/consummatory pleasure
Measured: Baseline, 6-month follow-up, 12-month follow-up
Life Events and Difficulties Schedule
Measure of acute events, difficulties, stressors
Measured: Baseline, 6-month follow-up, 12-month follow-up
Longitudinal Interval Follow-Up Evaluation (LIFE) (Keller et al., 1987)
Retrospectively assesses different DSM-5 disorders, social and occupational functioning, and life satisfaction over the past 6 months
Measured: 6-month follow-up, 12-month follow-up
Columbia-Suicide Severity Rating Scale
Suicide assessment
Measured: Baseline, 6-month follow-up, 12-month follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2022
- Study start1 Feb 2025
- Primary completion31 Mar 2027 (estimated)
- Study completion31 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Depressive Disorder, MajorStudies 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 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 112 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mclean Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH), Massachusetts General Hospital, Massachusetts Institute of Technology, University of Washington, Brown University
- Responsible party
- Principal investigator, Diego Pizzagalli, Mclean Hospital
- Investigators
- Diego Pizzagalli, Ph.D., Principal investigator, Mclean Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05232032
- Sponsor's protocol ID
- 2024P002715
- Other IDs
- 5P50MH119467-02
- Status last verified
- May 2026
- First submitted
- 1 Feb 2022
- Last updated
- 18 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Through the Conte Center website, we will share de-identified data and tools with the scientific community (e.g., code developed by the Computational Modeling Core). In close collaboration with NIMH, we will develop a certification similar to the "NIMH Data Archive Data Use Certification" currently used by NIMH. Through the National Database for Clinical Trials Related to Mental Illness, we will share five principal human datasets generated within the Conte Center: (1) Clinical rating scales and self-report scales of affect, mood, symptoms and functioning; (2) Behavioral performance during approach-avoidance tasks; (3) Electrophysiological data; (4) Functional magnetic resonance imaging data; and (5) Hormonal (cortisol) responses. Through ClinicalTrials.gov, we will share the primary and secondary outcomes.
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmaco-Neuroimaging Studies of Approach/Avoidance Behaviors and Post-Mortem Studies: Study 1.1. (Pharmacological Manipulation)
- ClinicalTrials.gov ID
- NCT05232032
- Acronym / sponsor ID
- 2024P002715
- Conditions
- Depressive Disorder, Major, Anxiety Disorder
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 112 participants (estimated)
- Lead sponsor
- Mclean HospitalUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH), Massachusetts General Hospital, Massachusetts Institute of Technology, University of Washington, Brown University
- Study start
- 1 Feb 2025 (actual)
- Primary completion
- 31 Mar 2027 (estimated)
- Study completion
- 31 Mar 2027 (estimated)
- First posted
- 9 Feb 2022 (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 study will investigate whether a nociceptin receptor antagonist will normalize neural and behavioral processes of approach/avoidance decision-making in unmedicated individuals with major depressive disorder (MDD) and anxiety disorders. More specifically, the study aims to investigate dysregulation within (1) corticostriatal-midbrain circuitry and (2) nociceptin/orphanin FQ peptide and the nociceptin receptor (NOPR).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Participants with MDD or an anxiety disorder receiving the nociceptin receptor antagonist | Experimental | Drug: Nociceptin Receptor Antagonist, Device: Aversive stimuliAfter a diagnostic interview (determining the presence of MDD or an anxiety disorder) and collection of blood for Orphanin FQ/Nociceptin assays, participants will receive the nociceptin receptor antagonist. Participants will then complete an approach/avoidance task. Functional magnetic resonance imagining (fMRI) will begin 2 hours after the nociceptin receptor antagonist is administered. |
| Participants with MDD or an anxiety disorder receiving the placebo | Placebo comparator | Device: Aversive stimuliAfter a diagnostic interview (determining the presence of MDD or an anxiety disorder) and collection of blood for Orphanin FQ/Nociceptin assays, participants will receive the placebo. Participants will then complete an approach/avoidance task. fMRI will begin 2 hours after the placebo is administered. |
| Healthy controls receiving the nociceptin receptor antagonist | Experimental | Drug: Nociceptin Receptor Antagonist, Device: Aversive stimuliAfter a diagnostic interview (determining healthy control status) and collection of blood for Orphanin FQ/Nociceptin assays, participants will receive a nociceptin receptor antagonist. Participants will then complete an approach/avoidance task. fMRI will begin 2 hours after the nociceptin receptor antagonist is administered. |
| Healthy controls receiving the placebo | Placebo comparator | Device: Aversive stimuliAfter a diagnostic interview (determining healthy control status) and collection of blood for Orphanin FQ/Nociceptin assays, participants will receive the placebo. Participants will then complete an approach/avoidance task. fMRI will begin 2 hours after the placebo is administered. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- DSM-5 diagnostic criteria for MDD, Generalized Anxiety Disorder, Social Phobia, Panic Disorder, Post Traumatic Stress (diagnosed using the SCID-5)
- Written informed consent
- For MDD subjects, a baseline Hamilton Depression Rating Scale score > 16 (17-item version)
- Right-handed
- Has a smartphone (iPhone or Android) (needed for Ecological Momentary Assessment)
Key exclusion criteria (15 listed)
- Subjects with suicidal ideation where outpatient treatment is determined unsafe by the study clinician
- Pregnant women or women of childbearing potential who are not using a medically accepted means of contraception
- Serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic or hematologic disease
- History of seizure disorder
- History or current diagnosis of any of the following DSM-IV psychiatric illnesses: organic mental disorder, schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorders not otherwise specified, bipolar disorder, obsessive-compulsive disorder, patients with mood congruent or mood incongruent psychotic features, substance dependence, substance abuse within the last 12 months (with the exception of cocaine or stimulant abuse; which will lead to exclusion)
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 |
|---|---|---|
| Nociceptin Receptor AntagonistAlso: BTRX-246040Participants in the experimental arms will receive 40 mg of the nociceptin receptor antagonist. Peak concentrations are achieved 2-4 hours post-administration. | Drug | Healthy controls receiving the nociceptin receptor antagonist, Participants with MDD or an anxiety disorder receiving the nociceptin receptor antagonist |
| Aversive stimuliAs part of the approach/avoidance task, electrotactile stimulation will be used. The aversive stimulus is delivered in the form of a mild half-second stimulation to the ankle, calibrated to a subjective threshold that is uncomfortable but not painful. This stimulation is delivered by Digitimer DS8R Constant Current Stimulator (Digitimer North America, LLC. Ft. Lauderdale, FL). Its previous model, DS71, has been safely implemented in studies within Massachusetts General Hospital (Milad et al., 2013). | Device | Healthy controls receiving the nociceptin receptor antagonist, Healthy controls receiving the placebo, Participants with MDD or an anxiety disorder receiving the nociceptin receptor antagonist, Participants with MDD or an anxiety disorder receiving the placebo |
Primary outcome
Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (SCID-5)
Time frame: Baseline
Diagnostic assessment
Magnetic Resonance Imagining
Time frame: Within 30 days of the clinical interview
Both structural and functional brain images
Approach/Avoidance Task
Time frame: During the MRI scan
A novel behavioral task assessing approach/avoidance decision-making
Orphanin FQ/Nociceptin assays (using blood samples)
Time frame: On the day of the MRI scan
Measure of Orphanin FQ/Nociceptin
10 secondary outcomes
Beck Depression Inventory-II
Time frame: Baseline, 6-month follow-up, 12-month follow-up
Hamilton Rating Scale for Depression
Time frame: Baseline, 6-month follow-up, 12-month follow-up
Perceived Stress Scale
Time frame: Baseline, 6-month follow-up, 12-month follow-up
Snaith Hamilton Pleasure Scale
Time frame: Baseline, 6-month follow-up, 12-month follow-up
Medical Outcome Survey- Short Form
Time frame: Baseline, 6-month follow-up, 12-month follow-up
Quality of Life Enjoyment and Satisfaction Questionnaire
Time frame: Baseline, 6-month follow-up, 12-month follow-up
Temporal Experience of Pleasure Scale
Time frame: Baseline, 6-month follow-up, 12-month follow-up
Life Events and Difficulties Schedule
Time frame: Baseline, 6-month follow-up, 12-month follow-up
Longitudinal Interval Follow-Up Evaluation (LIFE) (Keller et al., 1987)
Time frame: 6-month follow-up, 12-month follow-up
Columbia-Suicide Severity Rating Scale
Time frame: Baseline, 6-month follow-up, 12-month follow-up
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2026.
- Individual participant dataSharing planned: Yes. Through the Conte Center website, we will share de-identified data and tools with the scientific community (e.g., code developed by the Computational Modeling Core). In close collaboration with NIMH, we will develop a certification similar to the "NIMH Data Archive Data Use Certification" currently used by NIMH. Through the National Database for Clinical Trials Related to Mental Illness, we will share five principal human datasets generated within the Conte Center: (1) Clinical rating scales and self-report scales of affect, mood, symptoms and functioning; (2) Behavioral performance during approach-avoidance tasks; (3) Electrophysiological data; (4) Functional magnetic resonance imaging data; and (5) Hormonal (cortisol) responses. Through ClinicalTrials.gov, we will share the primary and secondary outcomes.
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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.
Diego 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?
A Phase 2 study testing Nociceptin Receptor Antagonist and Aversive stimuli in people with Depressive Disorder, Major and Anxiety 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 11 inclusion and 15 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: looking for participants now, as of the sponsor's last update on 18 May 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ethan M Zhang, BA (617-855-4434, ezhang24@mclean.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (SCID-5) (time frame: Baseline). The study lists 4 primary outcomes in all. 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 18 May 2026.