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

Sponsor
Georges El Fakhri (Other)
Overall Status
Recruiting
CT.gov ID
NCT05630963
Collaborator
National Institute of Mental Health (NIMH) (NIH)
228
1
62
3.7

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Device: Aversive stimuli
  • Drug: PET radiotracer

Detailed Description

The overarching goals of this research are to investigate: (1) the activity of the Nociceptin/Orphanin FQ receptor system among individuals with current or remitted MDD; (2) neural foundations of approach/avoidance behaviors in current or remitted MDDs; (3) stress-induced inflammation in individuals with remitted MDD; (4) neural markers that predict future disease course.

This will be achieved through an innovative method of using functional magnetic resonance imaging (fMRI) during an approach/avoidance decision-making task, in addition to a resting positron emission tomography (PET) scan.

Study Design

Study Type:
Observational
Anticipated Enrollment :
228 participants
Observational Model:
Case-Control
Time Perspective:
Prospective
Official Title:
Beyond Monoamines: The Role of the Nociceptin/Orphanin FQ Receptor in Major Depression
Actual Study Start Date :
Dec 29, 2021
Anticipated Primary Completion Date :
Oct 28, 2026
Anticipated Study Completion Date :
Feb 28, 2027

Arms and Interventions

Arm Intervention/Treatment
MDD subjects

Subjects diagnosed with Major Depression Disorder

Device: Aversive stimuli
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).

Drug: PET radiotracer
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.

Remitted MDD subjects

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

Device: Aversive stimuli
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).

Drug: PET radiotracer
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

Subjects with no history of known neurological and psychiatric illness.

Device: Aversive stimuli
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).

Drug: PET radiotracer
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.

Outcome Measures

Primary Outcome Measures

  1. Clinical Interview [Baseline]

    For assessing psychological state

  2. Behavioral Performance on the Probabilistic Reward Task (PRT) [Baseline]

    the PRT assesses individuals' ability to learn from rewards

  3. MRI Data [within 30 days of Screening Visit]

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

  4. Salivary Cortisol [Baseline]

    For assessing stress level

  5. PET Data [within 30 days of Screening Visit]

    For assessing the Nociceptin/Oprhanin FQ receptor system activity

  6. Arterial blood data [Baseline]

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

  7. Follow-up Clinical Interviews [Change from Baseline at 6 months and 12 months after the PET visit]

    To assess psychological state changes

Secondary Outcome Measures

  1. Beck Depression Inventory-II (BDI) [Change from Baseline at 6 months and 12 months after the PET visit]

    self-report measure of depressive symptoms

  2. Childhood Trauma Questionnaire (CTQ) [Baseline]

    self-report measure of childhood trauma

  3. Medical Outcome Survey-Short form (SF-36) [Change from Baseline at 6 months and 12 months after the PET visit]

    self-report with subscales measuring physical functioning, physical role functioning, social functioning, etc.

  4. Perceived Stress Scale (PSS) [Change from Baseline at 6 months and 12 months after the PET visit]

    self-report measure of stress levels

  5. Positive and Negative Affect Schedule (PANAS) [Baseline]

    self-report measure of positive and negative affect

  6. Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) [Change from Baseline at 6 months and 12 months after the PET visit]

    self-report measure of satisfaction and enjoyment across domains (e.g., work, leisure, social relations)

  7. Snaith Hamilton Pleasure Scale (SHAPS) [Change from Baseline at 6 months and 12 months after the PET visit]

    self-report measure of pleasure

  8. Thought and Feeling Questionnaire (TFQ) [Baseline]

    self-report measure of perception of being stuck in difficult situations

  9. Defeat Scale (DS) [Baseline]

    self-report measure of perception of defeat

  10. Questionnaire of Unpredictability in Childhood (QUIC) [Change from Baseline at 6 months and 12 months after the PET visit]

    self-report measure of unpredictability of parental environment growing up

  11. Mood and Anxiety Symptom Questionnaire (MASQ) [Baseline]

    self-report measure of mood symptom severity including 4 subscales related to depression and anxiety

  12. State-Trait Anxiety Inventory (STAI) [Baseline]

    Measures and differentiates between anxiety

  13. PRT Post-task Questionnaire [Baseline]

    self-report measure of participants' thoughts regarding the PRT task stimuli

  14. Temporal Experience of Pleasure Scale (TEPS) [Change from Baseline at 6 months and 12 months after the PET visit]

    self-report measure of ability to want and enjoy rewards

  15. Columbia-Suicide Severity Rating Scale (C-SSRS) [Baseline]

    clinical measure of suicidality

  16. Hamilton-Depression Rating Scale (HAMD-17) [Change from Baseline at 6 months and 12 months after the PET visit]

    clinical measure of depression severity

  17. Quick Inventory of Depressive Symptomatology (QIDS) [Change from Baseline at 6 months and 12 months after the PET visit]

    clinical measure of depression severity

  18. Cognitive-Behavioral Avoidance Scale (CBAS) [Baseline]

    self-report measure of trait avoidance

  19. Stress and Adversity Inventory (STRAIN) [Change from Baseline at 12 months after the PET visit]

    self-report measure of lifetime exposure to acute and chronic stress that may affect mental and physical health

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 45 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria for all participants:
  • 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)

Inclusion Criteria for "Remitted MDD" group:
  • Meets inclusion criteria for all subjects, plus:

  • History of MDD as defined by DSM-5

  • Absence of anxiety disorder for the past two months

Inclusion Criteria for "Current MDD" group:
  • Meets inclusion criteria for all subjects, plus:

  • Presence of MDD as defined by DSM-5

  • Absence of anxiety disorder for the past two months

Exclusion Criteria for all participants:
  • 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

  • Contraindications for arterial line (e.g., abnormal result on Allen test, Raynaud's syndrome, history of anemia or bleeding disorder, history of fainting from blood draws).

Contacts and Locations

Locations

Site City State Country Postal Code
1 McLean Hospital Belmont Massachusetts United States 02478

Sponsors and Collaborators

  • Georges El Fakhri
  • National Institute of Mental Health (NIMH)

Investigators

  • Principal Investigator: Diego Pizzagalli, PhD, Mclean Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Georges El Fakhri, Nathaniel & Diana Alpert Professor of Radiology, Harvard Medical School, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT05630963
Other Study ID Numbers:
  • 2018P000318
  • 4R37MH068376-17
First Posted:
Nov 30, 2022
Last Update Posted:
Dec 2, 2022
Last Verified:
Dec 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Dec 2, 2022