Clinical trial NCT05232032: Pharmaco-Neuroimaging Studies of Approach/Avoidance Behaviors and Post-Mortem Studies: Pharmacological Manipulation
Official title: Pharmaco-Neuroimaging Studies of Approach/Avoidance Behaviors and Post-Mortem Studies: Study 1.1. (Pharmacological Manipulation)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Depressive Disorder, Major
Anxiety Disorder
Lead sponsor: Mclean Hospital
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
name: Massachusetts General Hospital
name: Massachusetts Institute of Technology
name: University of Washington
name: Brown University
First posted: 2022-02-09
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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).


Eligibility 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

Primary outcomes:
measure: Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (SCID-5)
timeFrame: Baseline
measure: Magnetic Resonance Imagining
timeFrame: Within 30 days of the clinical interview
measure: Approach/Avoidance Task
timeFrame: During the MRI scan
measure: Orphanin FQ/Nociceptin assays (using blood samples)
timeFrame: On the day of the MRI scan
Secondary outcomes:
measure: Beck Depression Inventory-II
timeFrame: Baseline, 6-month follow-up, 12-month follow-up
measure: Hamilton Rating Scale for Depression
timeFrame: Baseline, 6-month follow-up, 12-month follow-up
measure: Perceived Stress Scale
timeFrame: Baseline, 6-month follow-up, 12-month follow-up
measure: Snaith Hamilton Pleasure Scale
timeFrame: Baseline, 6-month follow-up, 12-month follow-up
measure: Medical Outcome Survey- Short Form
timeFrame: Baseline, 6-month follow-up, 12-month follow-up
measure: Quality of Life Enjoyment and Satisfaction Questionnaire
timeFrame: Baseline, 6-month follow-up, 12-month follow-up
measure: Temporal Experience of Pleasure Scale
timeFrame: Baseline, 6-month follow-up, 12-month follow-up
measure: Life Events and Difficulties Schedule
timeFrame: Baseline, 6-month follow-up, 12-month follow-up
measure: Longitudinal Interval Follow-Up Evaluation (LIFE) (Keller et al., 1987)
timeFrame: 6-month follow-up, 12-month follow-up
measure: Columbia-Suicide Severity Rating Scale
timeFrame: Baseline, 6-month follow-up, 12-month follow-up
Other outcomes:
Locations:
Study officials:
affiliation: Mclean Hospital
name: Diego Pizzagalli, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: