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

Depressive Disorder, Major Clinical Trial

Official title:

Pharmaco-Neuroimaging Studies of Approach/Avoidance Behaviors and Post-Mortem Studies: Study 1.1. (Pharmacological Manipulation)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05232032
• Other study ID #: 5P50MH119467-02
• Secondary ID: 5P50MH119467-02
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: August 1, 2024
• Est. completion date: March 31, 2025

Study information

• Verified date: May 2024
• Source: Mclean Hospital
• Contact: Emma Palermo, BA
• Phone: 617-855-4412
• Email: ehpalermo[@]mclean.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 112
• Est. completion date: March 31, 2025
• Est. primary completion date: March 31, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Anxiety Disorder
• Anxiety Disorders
• Depressive Disorder
• Depressive Disorder, Major

Intervention

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., 2013).

Locations

Country	Name	City	State
n/a

Sponsors (6)

Lead Sponsor	Collaborator
Mclean Hospital	Brown University, Massachusetts General Hospital, Massachusetts Institute of Technology, National Institute of Mental Health (NIMH), University of Washington

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (SCID-5)	Diagnostic assessment	Baseline
Primary	Magnetic Resonance Imagining	Both structural and functional brain images	Within 30 days of the clinical interview
Primary	Approach/Avoidance Task	A novel behavioral task assessing approach/avoidance decision-making	During the MRI scan
Primary	Orphanin FQ/Nociceptin assays (using blood samples)	Measure of Orphanin FQ/Nociceptin	On the day of the MRI scan
Secondary	Beck Depression Inventory-II	21-item measure of depression severity; scores range from 0 to 63; higher scores indicate higher depression severity	Baseline, 6-month follow-up, 12-month follow-up
Secondary	Hamilton Rating Scale for Depression	17-item measure of depression severity; scores range from 0 to 34; higher scores indicate higher depression severity	Baseline, 6-month follow-up, 12-month follow-up
Secondary	Perceived Stress Scale	14-item measure of stress appraisal; scores range from 0 to 56; higher scores indicate higher perceived stress	Baseline, 6-month follow-up, 12-month follow-up
Secondary	Snaith Hamilton Pleasure Scale	14-item measure of anhedonia; scores range from 14 to 56; higher scores indicate higher anhedonia	Baseline, 6-month follow-up, 12-month follow-up
Secondary	Medical Outcome Survey- Short Form	36-item measure of physical and social functioning; score range from 36 to 149; higher scores indicate higher physical and social functioning	Baseline, 6-month follow-up, 12-month follow-up
Secondary	Quality of Life Enjoyment and Satisfaction Questionnaire	16-item measure of satisfaction and enjoyment across domains (e.g., work, interpersonal); scores range from 16 to 80; higher scores indicate higher life enjoyment and satisfaction	Baseline, 6-month follow-up, 12-month follow-up
Secondary	Temporal Experience of Pleasure Scale	24-item measure of anticipatory and consummatory pleasure; scores range from 24 to 144; higher scores indicate higher anticipatory/consummatory pleasure	Baseline, 6-month follow-up, 12-month follow-up
Secondary	Life Events and Difficulties Schedule	Measure of acute events, difficulties, stressors	Baseline, 6-month follow-up, 12-month follow-up
Secondary	Longitudinal Interval Follow-Up Evaluation (LIFE) (Keller et al., 1987)	Retrospectively assesses different DSM-5 disorders, social and occupational functioning, and life satisfaction over the past 6 months	6-month follow-up, 12-month follow-up
Secondary	Columbia-Suicide Severity Rating Scale	Suicide assessment	Baseline, 6-month follow-up, 12-month follow-up