Pharmaco-Neuroimaging Studies of Approach/Avoidance Behaviors and Post-Mortem Studies: Pharmacological Manipulation

NCT ID: NCT05232032

Last Updated: 2025-11-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

112 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-02-01

Study Completion Date

2025-12-31

Brief Summary

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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).

Detailed Description

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Conditions

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Depressive Disorder, Major Anxiety Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Participants with MDD or an anxiety disorder receiving the nociceptin receptor antagonist

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.

Group Type EXPERIMENTAL

Nociceptin Receptor Antagonist

Intervention Type DRUG

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

Aversive stimuli

Intervention Type 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).

Participants with MDD or an anxiety disorder receiving the placebo

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.

Group Type PLACEBO_COMPARATOR

Aversive stimuli

Intervention Type 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).

Healthy controls receiving the nociceptin receptor antagonist

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.

Group Type EXPERIMENTAL

Nociceptin Receptor Antagonist

Intervention Type DRUG

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

Aversive stimuli

Intervention Type 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).

Healthy controls receiving the placebo

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.

Group Type PLACEBO_COMPARATOR

Aversive stimuli

Intervention Type 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).

Interventions

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Nociceptin Receptor Antagonist

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

Intervention Type DRUG

Aversive stimuli

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).

Intervention Type DEVICE

Other Intervention Names

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BTRX-246040

Eligibility Criteria

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Inclusion Criteria

* 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)

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute of Mental Health (NIMH)

NIH

Sponsor Role collaborator

Massachusetts General Hospital

OTHER

Sponsor Role collaborator

Massachusetts Institute of Technology

OTHER

Sponsor Role collaborator

University of Washington

OTHER

Sponsor Role collaborator

Brown University

OTHER

Sponsor Role collaborator

Mclean Hospital

OTHER

Sponsor Role lead

Responsible Party

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Diego Pizzagalli

Professor, Department of Psychiatry, Harvard Medical School, McLean Hospital, McLean Hospital

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Diego Pizzagalli, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Mclean Hospital

Locations

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Mclean Hospital

Belmont, Massachusetts, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Ethan M Zhang, BA

Role: CONTACT

Phone: 617-855-4434

Email: [email protected]

David Crowley, ALM

Role: CONTACT

Phone: 617-855-4432

Email: [email protected]

Facility Contacts

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Ethan Zhang, BA

Role: primary

David Crowley, ALM

Role: backup

Other Identifiers

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5P50MH119467-02

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2024P002715

Identifier Type: -

Identifier Source: org_study_id