Depression - Major Depressive DisorderPhase 2NCT06786637
Investigating the Protective Impact of LY-2940094 on Stress-induced Depression- and Anxiety-related Phenotypes in Humans
A Phase 2 study testing Nociceptin Receptor Antagonist (LY-2940094) and DS8R Biphasic Constant Current Stimulator in people with Depression - Major Depressive Disorder and Anxiety, run by Mclean Hospital.
Trial summary
This project will integrate pharmacological and psychophysiological methodology to mechanistically investigate, in humans, the role of N/OFQ in laboratory phenotypes of both disorders. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Depression - Major Depressive Disorder, Anxiety, Stress
- What is being tested?
- Nociceptin Receptor Antagonist (LY-2940094) and DS8R Biphasic Constant Current Stimulator
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jun 2025to Aug 2026
- Phase
- Phase 2
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
- Absence of any medications for at least 3 weeks
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)
Show all 14Show fewer
- 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
- Abnormal ECG and lab results
- History of seizure disorder or currently on anticonvulsants
About this study
Official title: A Combined Investigation of the Protective Impact of the NOF/Q Antagonist LY-2940094 on Stress-induced Depression- and Anxiety-related Phenotypes in Humans
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.
- Conditions
- Depression - Major Depressive Disorder, Anxiety, Stress
- Being tested
- Nociceptin Receptor Antagonist (LY-2940094), DS8R Biphasic Constant Current Stimulator
- Medical subject headings
- Anxiety Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nociceptin Receptor Antagonist (LY-2940094)Drug
Also called Nociceptin Receptor Antagonist (BTRX-246040), Nociceptin Receptor Antagonist (C220614004-FP)
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.
DS8R Biphasic Constant Current StimulatorDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| Participants receiving the nociceptin receptor antagonist | Experimental | 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. Receives: Drug: Nociceptin Receptor Antagonist (LY-2940094); Device: DS8R Biphasic Constant Current Stimulator |
| Participants receiving the placebo | Placebo comparator | 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. Receives: Device: DS8R Biphasic Constant Current Stimulator |
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)
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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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).
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2025
- Study startJun 2025 (estimated)
- Primary completionJan 2026 (estimated)
- Study completionAug 2026 (estimated)
Why it stopped: PI transferred to a different research institution and local institution would not allow to continue the study. Transfer of the study to a different study site not possible because of unique requirements of resources (e.g., nociceptin anatagonist)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Depression - 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 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mclean Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Manuel Kuhn, Mclean Hospital
- Investigators
- Manuel Kuhn, Ph.D., Principal investigator, Mclean Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06786637
- Sponsor's protocol ID
- 2023A062574
- Other IDs
- 5P50MH119467-05
- Status last verified
- Sep 2025
- First submitted
- 7 Jan 2025
- Last updated
- 25 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Through NIMH Data Archive and ClinicalTrials.gov, we will share the primary and secondary outcomes.
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Combined Investigation of the Protective Impact of the NOF/Q Antagonist LY-2940094 on Stress-induced Depression- and Anxiety-related Phenotypes in Humans
- ClinicalTrials.gov ID
- NCT06786637
- Acronym / sponsor ID
- 2023A062574
- Conditions
- Depression - Major Depressive Disorder, Anxiety, Stress
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: PI transferred to a different research institution and local institution would not allow to continue the study. Transfer of the study to a different study site not possible because of unique requirements of resources (e.g., nociceptin anatagonist)
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Mclean HospitalUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Jun 2025 (estimated)
- Primary completion
- Jan 2026 (estimated)
- Study completion
- Aug 2026 (estimated)
- First posted
- 22 Jan 2025 (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.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Participants receiving the nociceptin receptor antagonist | Experimental | Drug: Nociceptin Receptor Antagonist (LY-2940094), Device: DS8R Biphasic Constant Current StimulatorAfter 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. |
| Participants receiving the placebo | Placebo comparator | Device: DS8R Biphasic Constant Current StimulatorAfter 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
- Absence of any medications for at least 3 weeks
Key exclusion criteria (14 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 Antagonist (LY-2940094)Also: Nociceptin Receptor Antagonist (BTRX-246040), Nociceptin Receptor Antagonist (C220614004-FP)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. | Drug | Participants receiving the nociceptin receptor antagonist |
| DS8R Biphasic Constant Current StimulatorAs 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. | Device | Participants receiving the nociceptin receptor antagonist, Participants 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
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.
Childhood Trauma Questionnaire (CTQ)
Time frame: Baseline
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.
List of Threatening Experiences Questionnaire (LTE)
Time frame: Baseline
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.
Combined Cue-Context Fear Conditioning Task: Subjective Fear Ratings
Time frame: Baseline
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).
Probabilistic Reward Task (PRT)
Time frame: Baseline
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.
Perceived Stress Scale
Time frame: Baseline
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.
Combined Cue-Context Fear Conditioning Task: Skin Conductance Responce (SCR)
Time frame: Baseline
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).
Combined Cue-Context Fear Conditioning Task: Fear-Potentiated Startle (FPS)
Time frame: Baseline
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).
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2025.
- Individual participant dataSharing planned: Yes. Through NIMH Data Archive and 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. This study is not recruiting at the moment.
Manuel Kuhn, Ph.D. principal investigator
Mclean Hospital
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nociceptin Receptor Antagonist (LY-2940094) and DS8R Biphasic Constant Current Stimulator in people with Depression - Major Depressive Disorder and Anxiety, run by Mclean Hospital.
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 3 inclusion and 14 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: withdrawn, as of the sponsor's last update on 25 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (SCID-5) (time frame: Baseline). The study lists 8 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 25 Sep 2025.