A Phase 2 interventional study of Nociceptin Receptor Antagonist (LY-2940094) and DS8R Biphasic Constant Current Stimulator in Depression - Major Depressive Disorder, Anxiety and Stress, sponsored by Mclean Hospital. Withdrawn. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-09-25.
Sponsored by Mclean Hospital · Phase 2, Interventional, and Basic science
This project will integrate pharmacological and psychophysiological methodology to mechanistically investigate, in humans, the role of N/OFQ in laboratory phenotypes of both disorders. Specifically, a N/OFQ receptor (NOPR) antagonist will be used to test the hypothesis that NOPR blockage will have antidepressant-like effects (potentiate reward processing); in addition, this study will also evaluate a key anxiety phenotype (fear learning). Finally, the impact of recent life stress on these processes will be assessed. Results will demonstrate the specificity of NOPR blockage on depressive phenotypes or suggest a common pathway for emotional disorders and will confirm a modulatory role of life stress.
4,868 studies on the registry are indexed under Anxiety Disorders; 1,390 are open to participants now.
Browse Anxiety Disorders 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.
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Exclusion Criteria:
After a diagnostic interview during the first visit, participants will receive the nociceptin receptor antagonist (LY-2940094) at the beginning of the second visit. Participants will then complete two computerized tasks (the Probabilistic Rewards Task (PRT) and a context fear conditioning paradigm). Tasks will begin 2 hours after the nociceptin receptor antagonist is administered.
Drug: Nociceptin Receptor Antagonist (LY-2940094) · Device: DS8R Biphasic Constant Current Stimulator
After a diagnostic interview during the first visit, participants will receive the placebo at the beginning of the second visit. Participants will then complete two computerized tasks (the Probabilistic Rewards Task (PRT) and a context fear conditioning paradigm). Tasks will begin 2 hours after the placebo is administered.
Device: DS8R Biphasic Constant Current Stimulator
Participants in the experimental arms will receive 40 mg of the nociceptin receptor antagonist LY-2940094. Peak concentrations are achieved 2-4 hours post-administration.
Also known as: Nociceptin Receptor Antagonist (BTRX-246040), Nociceptin Receptor Antagonist (C220614004-FP)
As part of the fear conditioning 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). This model has been safely implemented in studies within McLean Hospital and Massachusetts General Hospital.
Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (SCID-5)
The Structured Clinical Interview for DSM-5 (SCID-5) is a clinician-administered diagnostic tool used to assess and diagnose mental disorders based on DSM-5 criteria. The SCID-5 categorically identifies the presence or absence of specific diagnoses and does not provide numerical minimum/maximum values.
Time frame: Baseline
Childhood Trauma Questionnaire (CTQ)
The Childhood Trauma Questionnaire (CTQ) is a self-report tool assessing childhood emotional abuse, physical abuse, sexual abuse, emotional neglect, and physical neglect. Scores on each subscale range from 5 to 25, with a total score ranging from 25 to 125; higher scores indicate greater severity of childhood trauma.
Time frame: Baseline
List of Threatening Experiences Questionnaire (LTE)
The List of Threatening Experiences Questionnaire (LTE) is a self-report measure assessing the occurrence of stressful life events, such as bereavement, illness, or job loss, over a specified period. Scores range from 0 to 12, representing the number of endorsed events, with higher scores indicating a greater number of stressful experiences.
Time frame: Baseline
Combined Cue-Context Fear Conditioning Task: Subjective Fear Ratings
The combined cue-context fear conditioning task is a paradigm to assess fear learning and extinction in response to discrete cues as well as different contexts. Subjective ratings of fear are collected via visual analog scales throughout the task. Higher ratings mean higher expression of fear towards cues and contexts (min-max: 0-100).
Time frame: Baseline
Probabilistic Reward Task (PRT)
The Probabilistic Reward Task (PRT) is a behavioral measure assessing reward sensitivity and reinforcement learning. It evaluates participants' ability to modulate behavior based on probabilistic feedback associated with correct responses. The primary outcome is the response bias score, which ranges from negative values to positive values. Higher scores indicate a stronger bias toward the more frequently rewarded response, reflecting greater reward sensitivity and reinforcement learning. Lower or negative scores suggest impaired reward responsiveness, which is often associated with anhedonia or mood disorders.
Time frame: Baseline
Perceived Stress Scale
The Perceived Stress Scale (PSS) is a self-report measure assessing the degree to which situations in life are perceived as stressful over the past month. Scores range from 0 to 40, with higher scores indicating greater perceived stress.
Time frame: Baseline
Combined Cue-Context Fear Conditioning Task: Skin Conductance Responce (SCR)
The combined cue-context fear conditioning task is a paradigm to assess fear learning and extinction in response to discrete cues as well as different contexts. Skin conductance response (SCR) is a psychophysiological measure assessing objective levels of arousal. Skin conductance is measured in microsiemens (µS) and will be processed to quantify amplitude changes in response to task stimuli. Higher amplitudes indicate higher arousal levels in response to task stimuli (min: 0, max: none).
Time frame: Baseline
Combined Cue-Context Fear Conditioning Task: Fear-Potentiated Startle (FPS)
The combined cue-context fear conditioning task is a paradigm to assess fear learning and extinction in response to discrete cues as well as different contexts. Fear-potentiated startle (FPS) is a psychophysiological measure assessing objective levels of fear responses. FPS is a difference score between threat stimuli and neutral stimuli, both measured in microvolts (µV) and processed to quantify amplitude changes, in response to task stimuli. Higher FPS scores indicate higher fear levels towards the threat stimuli (min: none, max: none).
Time frame: Baseline
No study locations are listed for this record.
Plan to share: Yes — Through NIMH Data Archive and ClinicalTrials.gov, we will share the primary and secondary outcomes.
No publications or documents are linked to this record.
This study is withdrawn, as verified in Sep 2025. You cannot join it, but the record below documents what was studied.
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