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

Major Depressive Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05630963
• Other study ID #: 2018P000318
• Secondary ID: 4R37MH068376-17
• Status: Recruiting
• Start date: December 29, 2021
• Est. completion date: February 28, 2027

Study information

• Verified date: January 2024
• Source: Mclean Hospital
• Contact: Claire Anderson, BA
• Phone: 617-855-4290
• Email: canderson1[@]mclean.harvard.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 228
• Est. completion date: February 28, 2027
• Est. primary completion date: October 28, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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).

Related Conditions & MeSH terms

• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

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.

Locations

Country	Name	City	State
United States	McLean Hospital	Belmont	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Mclean Hospital	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical Interview	For assessing psychological state	Baseline
Primary	Behavioral Performance on the Probabilistic Reward Task (PRT)	the PRT assesses individuals' ability to learn from rewards	Baseline
Primary	MRI Data	For testing the neural correlates of approach-avoidance decision making behaviors	within 30 days of Screening Visit
Primary	Salivary Cortisol	For assessing stress level	Baseline
Primary	PET Data	For assessing the Nociceptin/Oprhanin FQ receptor system activity	within 30 days of Screening Visit
Primary	Arterial blood data	for PET modeling and assessing Nociceptin/Orphanin FQ levels in bloodstream	Baseline
Primary	Follow-up Clinical Interviews	To assess psychological state changes	Change from Baseline at 6 months and 12 months after the PET visit
Secondary	Beck Depression Inventory-II (BDI)	self-report measure of depressive symptoms	Change from Baseline at 6 months and 12 months after the PET visit
Secondary	Childhood Trauma Questionnaire (CTQ)	self-report measure of childhood trauma	Baseline
Secondary	Medical Outcome Survey-Short form (SF-36)	self-report with subscales measuring physical functioning, physical role functioning, social functioning, etc.	Change from Baseline at 6 months and 12 months after the PET visit
Secondary	Perceived Stress Scale (PSS)	self-report measure of stress levels	Change from Baseline at 6 months and 12 months after the PET visit
Secondary	Positive and Negative Affect Schedule (PANAS)	self-report measure of positive and negative affect	Baseline
Secondary	Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q)	self-report measure of satisfaction and enjoyment across domains (e.g., work, leisure, social relations)	Change from Baseline at 6 months and 12 months after the PET visit
Secondary	Snaith Hamilton Pleasure Scale (SHAPS)	self-report measure of pleasure	Change from Baseline at 6 months and 12 months after the PET visit
Secondary	Thought and Feeling Questionnaire (TFQ)	self-report measure of perception of being stuck in difficult situations	Baseline
Secondary	Defeat Scale (DS)	self-report measure of perception of defeat	Baseline
Secondary	Questionnaire of Unpredictability in Childhood (QUIC)	self-report measure of unpredictability of parental environment growing up	Change from Baseline at 6 months and 12 months after the PET visit
Secondary	Mood and Anxiety Symptom Questionnaire (MASQ)	self-report measure of mood symptom severity including 4 subscales related to depression and anxiety	Baseline
Secondary	State-Trait Anxiety Inventory (STAI)	Measures and differentiates between anxiety	Baseline
Secondary	PRT Post-task Questionnaire	self-report measure of participants' thoughts regarding the PRT task stimuli	Baseline
Secondary	Temporal Experience of Pleasure Scale (TEPS)	self-report measure of ability to want and enjoy rewards	Change from Baseline at 6 months and 12 months after the PET visit
Secondary	Columbia-Suicide Severity Rating Scale (C-SSRS)	clinical measure of suicidality	Baseline
Secondary	Hamilton-Depression Rating Scale (HAMD-17)	clinical measure of depression severity	Change from Baseline at 6 months and 12 months after the PET visit
Secondary	Quick Inventory of Depressive Symptomatology (QIDS)	clinical measure of depression severity	Change from Baseline at 6 months and 12 months after the PET visit
Secondary	Cognitive-Behavioral Avoidance Scale (CBAS)	self-report measure of trait avoidance	Baseline
Secondary	Stress and Adversity Inventory (STRAIN)	self-report measure of lifetime exposure to acute and chronic stress that may affect mental and physical health	Change from Baseline at 12 months after the PET visit