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Recruiting NCT05630963

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

— Observational Major Depressive Disorder

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Aversive stimuli, PET radiotracer.
Who it may be relevant to
Registry conditions: Major Depressive Disorder. Basic parameters: 18 years — 45 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United States
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

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Overview

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.

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.

Interventions

  • 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.

Primary outcome measures

  • Clinical Interview [Time frame: Baseline]
  • Behavioral Performance on the Probabilistic Reward Task (PRT) [Time frame: Baseline]
  • MRI Data [Time frame: within 30 days of Screening Visit]
  • Salivary Cortisol [Time frame: Baseline]
  • PET Data [Time frame: within 30 days of Screening Visit]
  • Arterial blood data [Time frame: Baseline]
  • Follow-up Clinical Interviews [Time frame: Change from Baseline at 6 months and 12 months after the PET visit]
Secondary outcome measures (12)
  • Beck Depression Inventory-II (BDI) [Time frame: Change from Baseline at 6 months and 12 months after the PET visit]
  • Childhood Trauma Questionnaire (CTQ) [Time frame: Baseline]
  • Medical Outcome Survey-Short form (SF-36) [Time frame: Change from Baseline at 6 months and 12 months after the PET visit]
  • Perceived Stress Scale (PSS) [Time frame: Change from Baseline at 6 months and 12 months after the PET visit]
  • Positive and Negative Affect Schedule (PANAS) [Time frame: Baseline]
  • Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) [Time frame: Change from Baseline at 6 months and 12 months after the PET visit]
  • Snaith Hamilton Pleasure Scale (SHAPS) [Time frame: Change from Baseline at 6 months and 12 months after the PET visit]
  • Thought and Feeling Questionnaire (TFQ) [Time frame: Baseline]
  • Defeat Scale (DS) [Time frame: Baseline]
  • Questionnaire of Unpredictability in Childhood (QUIC) [Time frame: Change from Baseline at 6 months and 12 months after the PET visit]
  • Mood and Anxiety Symptom Questionnaire (MASQ) [Time frame: Baseline]
  • State-Trait Anxiety Inventory (STAI) [Time frame: Baseline]

Eligibility criteria

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).

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

Healthy volunteers: Yes

Study design

Observational model
Case-control

Study locations

United States · 1 center
  • McLean Hospital — Belmont

Identifiers

NCT: NCT05630963 · 2018P000318 · 4R37MH068376-17

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗