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

Mass General Brigham

Status and phase: Enrolling; Phase 2

Conditions: Anxiety Disorder; Depressive Disorder, Major

Treatments: Drug: Nociceptin Receptor Antagonist; Device: Aversive stimuli

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05232032

2024P002715

5P50MH119467-02 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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).

Enrollment: 112 estimated patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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112 participants in 4 patient groups, including a placebo group

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

Experimental group

Description:

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.

Treatment:

Device: Aversive stimuli

Drug: Nociceptin Receptor Antagonist

Participants with MDD or an anxiety disorder receiving the placebo

Placebo Comparator group

Description:

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.

Treatment:

Device: Aversive stimuli

Healthy controls receiving the nociceptin receptor antagonist

Experimental group

Description:

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.

Treatment:

Device: Aversive stimuli

Drug: Nociceptin Receptor Antagonist

Healthy controls receiving the placebo

Placebo Comparator group

Description:

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.

Treatment:

Device: Aversive stimuli