A Phase 2 interventional study of Nociceptin Receptor Antagonist and Aversive stimuli in Depressive Disorder, Major and Anxiety Disorder, sponsored by Mclean Hospital. Recruiting at 1 site in United States. Open to participants aged 18 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-05-18.
Sponsored by Mclean Hospital · Phase 2, Interventional, and Basic science
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).
2,741 studies on the registry are indexed under Depressive Disorder, Major; 559 are open to participants now.
This study's planned enrollment of 112 is above the median of 80 across 2,283 interventional studies indexed under Depressive Disorder, Major.
Browse Depressive Disorder, Major studies →Mclean Hospital is the lead sponsor of 181 studies on the registry; 32 are open to participants now.
Of its 14 completed or terminated interventional studies of FDA-regulated products, 10 (71%) have results posted.
Counted across the registry records on this site, refreshed daily.
Inclusion criteria for MDD/anxiety disorder group:
Inclusion criteria for healthy controls:
Exclusion criteria for all participants:
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.
Drug: Nociceptin Receptor Antagonist · Device: Aversive stimuli
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.
Device: Aversive stimuli
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.
Drug: Nociceptin Receptor Antagonist · Device: Aversive stimuli
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.
Device: Aversive stimuli
Participants in the experimental arms will receive 40 mg of the nociceptin receptor antagonist. Peak concentrations are achieved 2-4 hours post-administration.
Also known as: BTRX-246040
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).
Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (SCID-5)
Diagnostic assessment
Time frame: Baseline
Magnetic Resonance Imagining
Both structural and functional brain images
Time frame: Within 30 days of the clinical interview
Approach/Avoidance Task
A novel behavioral task assessing approach/avoidance decision-making
Time frame: During the MRI scan
Orphanin FQ/Nociceptin assays (using blood samples)
Measure of Orphanin FQ/Nociceptin
Time frame: On the day of the MRI scan
Beck Depression Inventory-II
21-item measure of depression severity; scores range from 0 to 63; higher scores indicate higher depression severity
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Baseline, 6-month follow-up, 12-month follow-up
Life Events and Difficulties Schedule
Measure of acute events, difficulties, stressors
Time frame: 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
Time frame: 6-month follow-up, 12-month follow-up
Columbia-Suicide Severity Rating Scale
Suicide assessment
Time frame: Baseline, 6-month follow-up, 12-month follow-up
Plan to share: 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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