Major Depressive DisorderNCT05630963
Beyond Monoamines: The Role of the Nociceptin/Orphanin FQ Receptor in Major Depression
An observational study of Major Depressive Disorder, run by Mclean Hospital at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Aversive stimuli and PET radiotracer
- Type of treatment
- Injection or infusion, Medical device
- How many people
- 228 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Dec 2021to 28 Feb 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
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.
Who may be able to join
- 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)
- Meets inclusion criteria for all subjects, plus:
Show all 11Show fewer
- History of MDD as defined by DSM-5
- Absence of anxiety disorder for the past two months
- Meets inclusion criteria for all subjects, plus:
- Presence of MDD as defined by DSM-5
- Absence of anxiety disorder for the past two months
Who cannot join
- 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
Show all 16Show fewer
- 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).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
McLean Hospital
Belmont, Massachusetts, 02478
Tracy Lam, BS, 617-855-4437, clam@mclean.harvard.edu
About this study
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.
Read the 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.
- Conditions
- Major Depressive Disorder
- Being tested
- Aversive stimuli, PET radiotracer
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aversive stimuliDevice
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).
PET radiotracerDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| MDD subjects | Subjects diagnosed with Major Depression Disorder Receives: Device: Aversive stimuli; Drug: PET radiotracer | |
| Remitted MDD subjects | Subjects with a history of major depressive disorder episode in the past Receives: Device: Aversive stimuli; Drug: PET radiotracer | |
| Control subjects | Subjects with no history of known neurological and psychiatric illness. Receives: Device: Aversive stimuli; Drug: PET radiotracer |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Interview
For assessing psychological state
Measured: Baseline
Behavioral Performance on the Probabilistic Reward Task (PRT)
the PRT assesses individuals' ability to learn from rewards
Measured: Baseline
MRI Data
For testing the neural correlates of approach-avoidance decision making behaviors
Measured: within 30 days of Screening Visit
Salivary Cortisol
For assessing stress level
Measured: Baseline
PET Data
For assessing the Nociceptin/Oprhanin FQ receptor system activity
Measured: within 30 days of Screening Visit
Arterial blood data
for PET modeling and assessing Nociceptin/Orphanin FQ levels in bloodstream
Measured: Baseline
Follow-up Clinical Interviews
To assess psychological state changes
Measured: Change from Baseline at 6 months and 12 months after the PET visit
Secondary outcomes (19)
Beck Depression Inventory-II (BDI)
self-report measure of depressive symptoms
Measured: Change from Baseline at 6 months and 12 months after the PET visit
Childhood Trauma Questionnaire (CTQ)
self-report measure of childhood trauma
Measured: Baseline
Medical Outcome Survey-Short form (SF-36)
self-report with subscales measuring physical functioning, physical role functioning, social functioning, etc.
Measured: Change from Baseline at 6 months and 12 months after the PET visit
Perceived Stress Scale (PSS)
self-report measure of stress levels
Measured: Change from Baseline at 6 months and 12 months after the PET visit
Positive and Negative Affect Schedule (PANAS)
self-report measure of positive and negative affect
Measured: Baseline
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)
Measured: Change from Baseline at 6 months and 12 months after the PET visit
Snaith Hamilton Pleasure Scale (SHAPS)
self-report measure of pleasure
Measured: Change from Baseline at 6 months and 12 months after the PET visit
Thought and Feeling Questionnaire (TFQ)
self-report measure of perception of being stuck in difficult situations
Measured: Baseline
Defeat Scale (DS)
self-report measure of perception of defeat
Measured: Baseline
Questionnaire of Unpredictability in Childhood (QUIC)
self-report measure of unpredictability of parental environment growing up
Measured: Change from Baseline at 6 months and 12 months after the PET visit
Mood and Anxiety Symptom Questionnaire (MASQ)
self-report measure of mood symptom severity including 4 subscales related to depression and anxiety
Measured: Baseline
State-Trait Anxiety Inventory (STAI)
Measures and differentiates between anxiety
Measured: Baseline
PRT Post-task Questionnaire
self-report measure of participants' thoughts regarding the PRT task stimuli
Measured: Baseline
Temporal Experience of Pleasure Scale (TEPS)
self-report measure of ability to want and enjoy rewards
Measured: Change from Baseline at 6 months and 12 months after the PET visit
Columbia-Suicide Severity Rating Scale (C-SSRS)
clinical measure of suicidality
Measured: Baseline
Hamilton-Depression Rating Scale (HAMD-17)
clinical measure of depression severity
Measured: Change from Baseline at 6 months and 12 months after the PET visit
Quick Inventory of Depressive Symptomatology (QIDS)
clinical measure of depression severity
Measured: Change from Baseline at 6 months and 12 months after the PET visit
Cognitive-Behavioral Avoidance Scale (CBAS)
self-report measure of trait avoidance
Measured: Baseline
Stress and Adversity Inventory (STRAIN)
self-report measure of lifetime exposure to acute and chronic stress that may affect mental and physical health
Measured: Change from Baseline at 12 months after the PET visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2022
- Study start29 Dec 2021
- Primary completion28 Oct 2026 (estimated)
- Study completion28 Feb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 228 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mclean Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Diego Pizzagalli, Mclean Hospital
- Investigators
- Diego Pizzagalli, PhD, Principal investigator, Mclean Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05630963
- Sponsor's protocol ID
- 2018P000318
- Other IDs
- 4R37MH068376-17
- Status last verified
- Oct 2025
- First submitted
- 16 Nov 2022
- Last updated
- 21 Oct 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Beyond Monoamines: The Role of the Nociceptin/Orphanin FQ Receptor in Major Depression
- ClinicalTrials.gov ID
- NCT05630963
- Acronym / sponsor ID
- 2018P000318
- Conditions
- Major Depressive Disorder
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 228 participants (estimated)
- Lead sponsor
- Mclean HospitalUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 29 Dec 2021 (actual)
- Primary completion
- 28 Oct 2026 (estimated)
- Study completion
- 28 Feb 2027 (estimated)
- First posted
- 30 Nov 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| MDD subjects | – | Device: Aversive stimuli, Drug: PET radiotracerSubjects diagnosed with Major Depression Disorder |
| Remitted MDD subjects | – | Device: Aversive stimuli, Drug: PET radiotracerSubjects with a history of major depressive disorder episode in the past |
| Control subjects | – | Device: Aversive stimuli, Drug: PET radiotracerSubjects with no history of known neurological and psychiatric illness. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- 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.
Key inclusion criteria (11 listed)
- 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)
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Aversive stimuliElectrotactile 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). | Device | Control subjects, MDD subjects, Remitted MDD subjects |
| PET radiotracerA 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. | Drug | Control subjects, MDD subjects, Remitted MDD subjects |
Primary outcome
Clinical Interview
Time frame: Baseline
For assessing psychological state
Behavioral Performance on the Probabilistic Reward Task (PRT)
Time frame: Baseline
the PRT assesses individuals' ability to learn from rewards
MRI Data
Time frame: within 30 days of Screening Visit
For testing the neural correlates of approach-avoidance decision making behaviors
Salivary Cortisol
Time frame: Baseline
For assessing stress level
PET Data
Time frame: within 30 days of Screening Visit
For assessing the Nociceptin/Oprhanin FQ receptor system activity
Arterial blood data
Time frame: Baseline
for PET modeling and assessing Nociceptin/Orphanin FQ levels in bloodstream
Follow-up Clinical Interviews
Time frame: Change from Baseline at 6 months and 12 months after the PET visit
To assess psychological state changes
19 secondary outcomes
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
PRT Post-task Questionnaire
Time frame: Baseline
Temporal Experience of Pleasure Scale (TEPS)
Time frame: Change from Baseline at 6 months and 12 months after the PET visit
Columbia-Suicide Severity Rating Scale (C-SSRS)
Time frame: Baseline
Hamilton-Depression Rating Scale (HAMD-17)
Time frame: Change from Baseline at 6 months and 12 months after the PET visit
Quick Inventory of Depressive Symptomatology (QIDS)
Time frame: Change from Baseline at 6 months and 12 months after the PET visit
Cognitive-Behavioral Avoidance Scale (CBAS)
Time frame: Baseline
Stress and Adversity Inventory (STRAIN)
Time frame: Change from Baseline at 12 months after the PET visit
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Diego Pizzagalli, PhD principal investigator
Mclean Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Major Depressive Disorder, run by Mclean Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 21 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Tracy Lam, BS (617-855-4437, mclrew41study@mgb.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical Interview (time frame: Baseline). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2025.