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)

Overview

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).

Interventions

• Drug 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.
• Device 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., 20

Primary outcome measures

• Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (SCID-5) [Time frame: Baseline]
• Magnetic Resonance Imagining [Time frame: Within 30 days of the clinical interview]
• Approach/Avoidance Task [Time frame: During the MRI scan]
• Orphanin FQ/Nociceptin assays (using blood samples) [Time frame: On the day of the MRI scan]

Secondary outcome measures (10)

• Beck Depression Inventory-II [Time frame: Baseline, 6-month follow-up, 12-month follow-up]
• Hamilton Rating Scale for Depression [Time frame: Baseline, 6-month follow-up, 12-month follow-up]
• Perceived Stress Scale [Time frame: Baseline, 6-month follow-up, 12-month follow-up]
• Snaith Hamilton Pleasure Scale [Time frame: Baseline, 6-month follow-up, 12-month follow-up]
• Medical Outcome Survey- Short Form [Time frame: Baseline, 6-month follow-up, 12-month follow-up]
• Quality of Life Enjoyment and Satisfaction Questionnaire [Time frame: Baseline, 6-month follow-up, 12-month follow-up]
• Temporal Experience of Pleasure Scale [Time frame: Baseline, 6-month follow-up, 12-month follow-up]
• Life Events and Difficulties Schedule [Time frame: Baseline, 6-month follow-up, 12-month follow-up]
• Longitudinal Interval Follow-Up Evaluation (LIFE) (Keller et al., 1987) [Time frame: 6-month follow-up, 12-month follow-up]
• Columbia-Suicide Severity Rating Scale [Time frame: Baseline, 6-month follow-up, 12-month follow-up]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Basic science

Study locations

United States · 1 center

• Mclean Hospital — Belmont

Identifiers

NCT: NCT05232032 · 2024P002715 · 5P50MH119467-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗