NCT05232032

Brief 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. More specifically, the study aims to investigate dysregulation within (1) corticostriatal-midbrain circuitry and (2) nociceptin/orphanin FQ peptide and the nociceptin receptor (NOPR).

Trial Health

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Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
112

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Feb 2025

Shorter than P25 for phase_2

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 1, 2022

Completed
8 days until next milestone

First Posted

Study publicly available on registry

February 9, 2022

Completed
3 years until next milestone

Study Start

First participant enrolled

February 1, 2025

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 31, 2026

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 31, 2026

Completed
Last Updated

December 18, 2025

Status Verified

December 1, 2025

Enrollment Period

1.2 years

First QC Date

February 1, 2022

Last Update Submit

December 17, 2025

Conditions

Anxiety DisorderDepressive Disorder, Major

Outcome Measures

Primary Outcomes (4)

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

    Diagnostic assessment

    Baseline

  • Magnetic Resonance Imagining

    Both structural and functional brain images

    Within 30 days of the clinical interview

  • Approach/Avoidance Task

    A novel behavioral task assessing approach/avoidance decision-making

    During the MRI scan

  • Orphanin FQ/Nociceptin assays (using blood samples)

    Measure of Orphanin FQ/Nociceptin

    On the day of the MRI scan

Secondary Outcomes (10)

  • Beck Depression Inventory-II

    Baseline, 6-month follow-up, 12-month follow-up

  • Hamilton Rating Scale for Depression

    Baseline, 6-month follow-up, 12-month follow-up

  • Perceived Stress Scale

    Baseline, 6-month follow-up, 12-month follow-up

  • Snaith Hamilton Pleasure Scale

    Baseline, 6-month follow-up, 12-month follow-up

  • Medical Outcome Survey- Short Form

    Baseline, 6-month follow-up, 12-month follow-up

  • +5 more secondary outcomes

Study Arms (4)

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.

Drug: Nociceptin Receptor AntagonistDevice: 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.

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.

Drug: Nociceptin Receptor AntagonistDevice: 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.

Device: Aversive stimuli

Interventions

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).

Healthy controls receiving the nociceptin receptor antagonistHealthy controls receiving the placeboParticipants with MDD or an anxiety disorder receiving the nociceptin receptor antagonistParticipants with MDD or an anxiety disorder receiving the placebo
Nociceptin Receptor AntagonistDRUG

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
Healthy controls receiving the nociceptin receptor antagonistParticipants with MDD or an anxiety disorder receiving the nociceptin receptor antagonist

Eligibility Criteria

Age18 Years - 45 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • 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)
  • 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)

You may not qualify if:

  • 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 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Mclean Hospital

Belmont, Massachusetts, 02478, United States

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, MajorAnxiety Disorders

Condition Hierarchy (Ancestors)

Depressive DisorderMood DisordersMental Disorders

Study Officials

  • Diego Pizzagalli, Ph.D.

    Mclean Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Ethan M Zhang, BA

CONTACT

617-855-4434ezhang24@mclean.harvard.edu

David Crowley, ALM

CONTACT

617-855-4432djcrowley@mclean.harvard.edu

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor, Department of Psychiatry, Harvard Medical School, McLean Hospital, McLean Hospital

Study Record Dates

First Submitted

February 1, 2022

First Posted

February 9, 2022

Study Start

February 1, 2025

Primary Completion

March 31, 2026

Study Completion

March 31, 2026

Last Updated

December 18, 2025

Record last verified: 2025-12

Data Sharing

IPD Sharing
Will share

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.

Locations

US(1)