Beyond Monoamines: The Role of the Nociceptin/Orphanin FQ Receptor in Major Depression

NCT05630963 | Recruiting FDA Drug

• 2 other identifiers: 2018P0003184R37MH068376-17
• Study Type: observational
• Target: 228
• Locations: 1 country
• Sites: 1

Brief Summary

This study looks at the role of the Nociceptin/Orphanin FQ receptor system in the brain of individuals with current or past major depressive disorder (MDD). It also examines how individuals with a history of depression make certain decisions and which brain regions are involved in such decisions. Information collected through MRI, PET, biospecimens (i.e., blood, saliva) and behavioral tasks will be used to predict depressive symptoms in the future.

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (7)

• Clinical Interview

  For assessing psychological state

  Baseline

• Behavioral Performance on the Probabilistic Reward Task (PRT)

  the PRT assesses individuals' ability to learn from rewards

  Baseline

• MRI Data

  For testing the neural correlates of approach-avoidance decision making behaviors

  within 30 days of Screening Visit

• Salivary Cortisol

  For assessing stress level

  Baseline

• PET Data

  For assessing the Nociceptin/Oprhanin FQ receptor system activity

  within 30 days of Screening Visit

• Arterial blood data

  for PET modeling and assessing Nociceptin/Orphanin FQ levels in bloodstream

  Baseline

• Follow-up Clinical Interviews

  To assess psychological state changes

  Change from Baseline at 6 months and 12 months after the PET visit

Secondary Outcomes (19)

• Beck Depression Inventory-II (BDI)

  Change from Baseline at 6 months and 12 months after the PET visit

• Childhood Trauma Questionnaire (CTQ)

  Baseline

• Medical Outcome Survey-Short form (SF-36)

  Change from Baseline at 6 months and 12 months after the PET visit

• Perceived Stress Scale (PSS)

  Change from Baseline at 6 months and 12 months after the PET visit

• Positive and Negative Affect Schedule (PANAS)

  Baseline

Study Arms (3)

MDD subjects

Subjects diagnosed with Major Depression Disorder

Device: Aversive stimuli; Drug: PET radiotracer

Remitted MDD subjects

Subjects with a history of major depressive disorder episode in the past

Device: Aversive stimuli; Drug: PET radiotracer

Control subjects

Subjects with no history of known neurological and psychiatric illness.

Device: Aversive stimuli; Drug: PET radiotracer

Interventions

Aversive stimuli DEVICE

Electrotactile stimulation will be used as the aversive stimulus. 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 with previously MGH-approved IRB's (Milad et al., 2013).

Control subjects; MDD subjects; Remitted MDD subjects

PET radiotracer DRUG

A Nociceptin/Orphanin FQ ("N/OFQ") peptide tracer (\[11C\] NOP-1A) will be used as the PET radiotracer. Approximately 10 mCi of this tracer will be delivered intravenously as a slow bolus over 60 seconds with beginning of the PET imaging acquisition. Approximately 60 ml of blood will be drawn from an artery throughout the dynamic PET acquisition in order to measure the blood N/OFQ levels.

Control subjects; MDD subjects; Remitted MDD subjects

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

The subjects for this research will be 228 participants recruited from the community by the Center for Depression, Anxiety and Stress Research (Director: Dr. Diego Pizzagalli, Ph.D.). Demographically-matched participants will include: (1) 38 participants with current MDD; (2) 38 participants with past MDD; and (3) 38 healthy controls.

You may qualify if:

• All genders, races, and ethnic origins, aged between 18 and 45
• Capable of providing written informed consent, and fluent in English
• Right-handed
• Absence of any psychotropic medications for at least 2 weeks
• Has a smartphone (iPhone or Android) (needed for Ecological Momentary Assessment)
• History of MDD as defined by DSM-5
• Absence of anxiety disorder for the past two months
• Presence of MDD as defined by DSM-5
• Absence of anxiety disorder for the past two months

You may not qualify if:

• Subjects with suicidal ideation where outpatient treatment is determined unsafe by the study clinician. These patients will be immediately referred to appropriate clinical treatment
• Pregnant women or women of childbearing potential who are not using a medically accepted means of contraception (defined as oral contraceptive pill or implant, condom, diaphragm, spermicide, IUD, s/p tubal ligation, or partner with vasectomy)
• Serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic or hematologic disease
• History of seizure disorder
• History of psychiatric illnesses, other than depression or anxiety disorders among the Current MDD and Remitted MDD groups
• History of substance use disorder or alcohol use disorder (as these terms are defined by DSM-5); except depressed subjects may have a history of 'Mild' substance/alcohol use disorder only if it ended as least 12 months ago
• History of cocaine or stimulant use or dopaminergic drugs
• History or current diagnosis of dementia, or a score of \< 26 on the Mini Mental State Examination at the screening visit;
• 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 (ECT)
• Failure to meet standard MRI safety requirements
• Abnormal ECG and lab results
• History of seizure disorder

Sponsors & Collaborators

• Mclean Hospital: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

McLean Hospital

Belmont, Massachusetts, 02478, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Saliva samples are collected seven times over the course of the MRI visit to be assayed for salivary cortisol Blood samples are collected during the MRI visit-once before the scan and once after the scan-to processed for RNA, DNA, and serum. Processed samples will be analyzed for proinflammatory cytokines and transcription control levels.

MeSH Terms

Conditions

Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Diego Pizzagalli, PhD

  Mclean Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tracy Lam, BS

CONTACT

617-855-4437; mclrew41study@mgb.org

David Crowley, ALM

CONTACT

617-855-4432; djcrowley@mclean.harvard.edu

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Center for Depression, Anxiety and Stress Research

Study Record Dates

• First Submitted: November 16, 2022
• First Posted: November 30, 2022
• Study Start: December 29, 2021
• Primary Completion (Estimated): October 28, 2026
• Study Completion (Estimated): February 28, 2027
• Last Updated: October 21, 2025

Record last verified: 2025-10

Locations

US (1)