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NCT Number: NCT05232032

Pharmaco-Neuroimaging Studies of Approach/Avoidance Behaviors and Post-Mortem Studies: 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).

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Key information

Age range

18 year–45 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

for MDD/anxiety disorder group:

  • 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)

Inclusion criteria

for healthy controls:

  • 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)

Exclusion criteria

for all participants:

  • 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)
  • 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

Treatment and study plan

Nociceptin Receptor Antagonist

Drug

Participants in the experimental arms will receive 40 mg of the nociceptin receptor antagonist. Peak concentrations are achieved 2-4 hours post-administration.

Other names: BTRX-246040

Aversive stimuli

Device

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).

Primary outcomes

  1. Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (SCID-5)

    Time frame: Baseline

    Diagnostic assessment

  2. Magnetic Resonance Imagining

    Time frame: Within 30 days of the clinical interview

    Both structural and functional brain images

  3. Approach/Avoidance Task

    Time frame: During the MRI scan

    A novel behavioral task assessing approach/avoidance decision-making

  4. Orphanin FQ/Nociceptin assays (using blood samples)

    Time frame: On the day of the MRI scan

    Measure of Orphanin FQ/Nociceptin

Secondary outcomes

  1. Beck Depression Inventory-II

    Time frame: Baseline, 6-month follow-up, 12-month follow-up

    21-item measure of depression severity; scores range from 0 to 63; higher scores indicate higher depression severity

  2. Hamilton Rating Scale for Depression

    Time frame: Baseline, 6-month follow-up, 12-month follow-up

    17-item measure of depression severity; scores range from 0 to 34; higher scores indicate higher depression severity

  3. Perceived Stress Scale

    Time frame: Baseline, 6-month follow-up, 12-month follow-up

    14-item measure of stress appraisal; scores range from 0 to 56; higher scores indicate higher perceived stress

  4. Snaith Hamilton Pleasure Scale

    Time frame: Baseline, 6-month follow-up, 12-month follow-up

    14-item measure of anhedonia; scores range from 14 to 56; higher scores indicate higher anhedonia

  5. Medical Outcome Survey- Short Form

    Time frame: Baseline, 6-month follow-up, 12-month follow-up

    36-item measure of physical and social functioning; score range from 36 to 149; higher scores indicate higher physical and social functioning

  6. Quality of Life Enjoyment and Satisfaction Questionnaire

    Time frame: Baseline, 6-month follow-up, 12-month follow-up

    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

  7. Temporal Experience of Pleasure Scale

    Time frame: Baseline, 6-month follow-up, 12-month follow-up

    24-item measure of anticipatory and consummatory pleasure; scores range from 24 to 144; higher scores indicate higher anticipatory/consummatory pleasure

  8. Life Events and Difficulties Schedule

    Time frame: Baseline, 6-month follow-up, 12-month follow-up

    Measure of acute events, difficulties, stressors

  9. Longitudinal Interval Follow-Up Evaluation (LIFE) (Keller et al., 1987)

    Time frame: 6-month follow-up, 12-month follow-up

    Retrospectively assesses different DSM-5 disorders, social and occupational functioning, and life satisfaction over the past 6 months

  10. Columbia-Suicide Severity Rating Scale

    Time frame: Baseline, 6-month follow-up, 12-month follow-up

    Suicide assessment

Study contacts

Contact information is provided by the study sponsor or research team.

David Crowley, ALM

CONTACT

[email protected]

617-855-4432

Ethan M Zhang, BA

CONTACT

[email protected]

617-855-4434

Sponsors and collaborators

Lead sponsor

Mclean Hospital

Other

Collaborators

  • Brown University
  • Massachusetts General Hospital
  • Massachusetts Institute of Technology
  • National Institute of Mental Health (NIMH)
  • University of Washington

Registry information

Official study title

Pharmaco-Neuroimaging Studies of Approach/Avoidance Behaviors and Post-Mortem Studies: Study 1.1. (Pharmacological Manipulation)

Important dates

Study start
2025
Primary completion
2027
Study completion
2027
First posted
Feb 9, 2022
Registry last updated
May 18, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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