Back to resultsPharmaco-Neuroimaging Studies of Approach/Avoidance Behaviors and Post-Mortem Studies: Pharmacological Manipulation
Primary Purpose
Depressive Disorder, Major, Anxiety Disorder
Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Nociceptin Receptor Antagonist
Aversive stimuli
Sponsored by
About this trial
This is an interventional basic science trial for Depressive Disorder, Major
Eligibility Criteria
Inclusion criteria for MDD/anxiety disorder group:
- DSM-5 diagnostic criteria for MDD, Generalized Anxiety Disorder, Social Phobia, Panic Disorder, Post Traumatic Stress (diagnosed using the SCID-5)
- Written informed consent
- For MDD subjects, a baseline Hamilton Depression Rating Scale score > 16 (17-item version)
- Right-handed
- Has a smartphone (iPhone or Android) (needed for Ecological Momentary Assessment)
- Absence of any psychotropic medications for at least 2 weeks (6 weeks for fluoxetine, 6 months for neuroleptics, 2 weeks for benzodiazepines, 2 weeks for any other antidepressants)
Inclusion criteria for healthy controls:
- Absence of medical, neurological, and psychiatric illness (including alcohol and substance abuse), as assessed by subject history and a structured clinical interview (diagnosed using the SCID-5)
- Written informed consent
- Right-handed
- Absence of any medications for at least 3 weeks
- Has a smartphone (iPhone or Android) (needed for Ecological Momentary Assessment)
Exclusion criteria for all participants:
- Subjects with suicidal ideation where outpatient treatment is determined unsafe by the study clinician
- Pregnant women or women of childbearing potential who are not using a medically accepted means of contraception
- Serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic or hematologic disease
- History of seizure disorder
- History or current diagnosis of any of the following DSM-IV psychiatric illnesses: organic mental disorder, schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorders not otherwise specified, bipolar disorder, obsessive-compulsive disorder, patients with mood congruent or mood incongruent psychotic features, substance dependence, substance abuse within the last 12 months (with the exception of cocaine or stimulant abuse; which will lead to exclusion)
- History of cocaine or stimulant use (e.g., amphetamine, cocaine, methamphetamine)
- History of use of dopaminergic drugs (including methylphenidate)
- History or current diagnosis of dementia
- 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
- Failure to meet standard magnetic resonance imaging safety requirements
- Abnormal ECG and lab results
- History of seizure disorder or currently on anticonvulsants
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Arm Label
Participants with MDD or an anxiety disorder receiving the nociceptin receptor antagonist
Participants with MDD or an anxiety disorder receiving the placebo
Healthy controls receiving the nociceptin receptor antagonist
Healthy controls receiving the placebo
Arm Description
After a diagnostic interview (determining the presence of MDD or an anxiety disorder) and collection of blood for Orphanin FQ/Nociceptin assays, participants will receive the nociceptin receptor antagonist. Participants will then complete an approach/avoidance task. Functional magnetic resonance imagining (fMRI) will begin 2 hours after the nociceptin receptor antagonist is administered.
After a diagnostic interview (determining the presence of MDD or an anxiety disorder) and collection of blood for Orphanin FQ/Nociceptin assays, participants will receive the placebo. Participants will then complete an approach/avoidance task. fMRI will begin 2 hours after the placebo is administered.
After a diagnostic interview (determining healthy control status) and collection of blood for Orphanin FQ/Nociceptin assays, participants will receive a nociceptin receptor antagonist. Participants will then complete an approach/avoidance task. fMRI will begin 2 hours after the nociceptin receptor antagonist is administered.
After a diagnostic interview (determining healthy control status) and collection of blood for Orphanin FQ/Nociceptin assays, participants will receive the placebo. Participants will then complete an approach/avoidance task. fMRI will begin 2 hours after the placebo is administered.
Outcomes
Primary Outcome Measures
Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (SCID-5)
Diagnostic assessment
Magnetic Resonance Imagining
Both structural and functional brain images
Approach/Avoidance Task
A novel behavioral task assessing approach/avoidance decision-making
Orphanin FQ/Nociceptin assays (using blood samples)
Measure of Orphanin FQ/Nociceptin
Secondary Outcome Measures
Beck Depression Inventory-II
21-item measure of depression severity; scores range from 0 to 63; higher scores indicate higher depression severity
Hamilton Rating Scale for Depression
17-item measure of depression severity; scores range from 0 to 34; higher scores indicate higher depression severity
Perceived Stress Scale
14-item measure of stress appraisal; scores range from 0 to 56; higher scores indicate higher perceived stress
Snaith Hamilton Pleasure Scale
14-item measure of anhedonia; scores range from 14 to 56; higher scores indicate higher anhedonia
Medical Outcome Survey- Short Form
36-item measure of physical and social functioning; score range from 36 to 149; higher scores indicate higher physical and social functioning
Quality of Life Enjoyment and Satisfaction Questionnaire
16-item measure of satisfaction and enjoyment across domains (e.g., work, interpersonal); scores range from 16 to 80; higher scores indicate higher life enjoyment and satisfaction
Temporal Experience of Pleasure Scale
24-item measure of anticipatory and consummatory pleasure; scores range from 24 to 144; higher scores indicate higher anticipatory/consummatory pleasure
Life Events and Difficulties Schedule
Measure of acute events, difficulties, stressors
Longitudinal Interval Follow-Up Evaluation (LIFE) (Keller et al., 1987)
Retrospectively assesses different DSM-5 disorders, social and occupational functioning, and life satisfaction over the past 6 months
Columbia-Suicide Severity Rating Scale
Suicide assessment
Full Information
NCT ID
NCT05232032
First Posted
February 1, 2022
Last Updated
March 13, 2023
Sponsor
Mclean Hospital
Collaborators
National Institute of Mental Health (NIMH), Massachusetts General Hospital, Massachusetts Institute of Technology, University of Washington, Brown University
1. Study Identification
Unique Protocol Identification Number
NCT05232032
Brief Title
Pharmaco-Neuroimaging Studies of Approach/Avoidance Behaviors and Post-Mortem Studies: Pharmacological Manipulation
Official Title
Pharmaco-Neuroimaging Studies of Approach/Avoidance Behaviors and Post-Mortem Studies: Study 1.1. (Pharmacological Manipulation)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
July 1, 2023 (Anticipated)
Primary Completion Date
March 31, 2025 (Anticipated)
Study Completion Date
March 31, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mclean Hospital
Collaborators
National Institute of Mental Health (NIMH), Massachusetts General Hospital, Massachusetts Institute of Technology, University of Washington, Brown University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The study will investigate whether a nociceptin receptor antagonist will normalize neural and behavioral processes of approach/avoidance decision-making in unmedicated individuals with major depressive disorder (MDD) and anxiety disorders. More specifically, the study aims to investigate dysregulation within (1) corticostriatal-midbrain circuitry and (2) nociceptin/orphanin FQ peptide and the nociceptin receptor (NOPR).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Depressive Disorder, Major, Anxiety Disorder
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
112 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Participants with MDD or an anxiety disorder receiving the nociceptin receptor antagonist
Arm Type
Experimental
Arm Description
After a diagnostic interview (determining the presence of MDD or an anxiety disorder) and collection of blood for Orphanin FQ/Nociceptin assays, participants will receive the nociceptin receptor antagonist. Participants will then complete an approach/avoidance task. Functional magnetic resonance imagining (fMRI) will begin 2 hours after the nociceptin receptor antagonist is administered.
Arm Title
Participants with MDD or an anxiety disorder receiving the placebo
Arm Type
Placebo Comparator
Arm Description
After a diagnostic interview (determining the presence of MDD or an anxiety disorder) and collection of blood for Orphanin FQ/Nociceptin assays, participants will receive the placebo. Participants will then complete an approach/avoidance task. fMRI will begin 2 hours after the placebo is administered.
Arm Title
Healthy controls receiving the nociceptin receptor antagonist
Arm Type
Experimental
Arm Description
After a diagnostic interview (determining healthy control status) and collection of blood for Orphanin FQ/Nociceptin assays, participants will receive a nociceptin receptor antagonist. Participants will then complete an approach/avoidance task. fMRI will begin 2 hours after the nociceptin receptor antagonist is administered.
Arm Title
Healthy controls receiving the placebo
Arm Type
Placebo Comparator
Arm Description
After a diagnostic interview (determining healthy control status) and collection of blood for Orphanin FQ/Nociceptin assays, participants will receive the placebo. Participants will then complete an approach/avoidance task. fMRI will begin 2 hours after the placebo is administered.
Intervention Type
Drug
Intervention Name(s)
Nociceptin Receptor Antagonist
Other Intervention Name(s)
BTRX-246040
Intervention Description
Participants in the experimental arms will receive 40 mg of the nociceptin receptor antagonist. Peak concentrations are achieved 2-4 hours post-administration.
Intervention Type
Device
Intervention Name(s)
Aversive stimuli
Intervention Description
As part of the approach/avoidance task, electrotactile stimulation will be used. 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 within Massachusetts General Hospital (Milad et al., 2013).
Primary Outcome Measure Information:
Title
Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (SCID-5)
Description
Diagnostic assessment
Time Frame
Baseline
Title
Magnetic Resonance Imagining
Description
Both structural and functional brain images
Time Frame
Within 30 days of the clinical interview
Title
Approach/Avoidance Task
Description
A novel behavioral task assessing approach/avoidance decision-making
Time Frame
During the MRI scan
Title
Orphanin FQ/Nociceptin assays (using blood samples)
Description
Measure of Orphanin FQ/Nociceptin
Time Frame
On the day of the MRI scan
Secondary Outcome Measure Information:
Title
Beck Depression Inventory-II
Description
21-item measure of depression severity; scores range from 0 to 63; higher scores indicate higher depression severity
Time Frame
Baseline, 6-month follow-up, 12-month follow-up
Title
Hamilton Rating Scale for Depression
Description
17-item measure of depression severity; scores range from 0 to 34; higher scores indicate higher depression severity
Time Frame
Baseline, 6-month follow-up, 12-month follow-up
Title
Perceived Stress Scale
Description
14-item measure of stress appraisal; scores range from 0 to 56; higher scores indicate higher perceived stress
Time Frame
Baseline, 6-month follow-up, 12-month follow-up
Title
Snaith Hamilton Pleasure Scale
Description
14-item measure of anhedonia; scores range from 14 to 56; higher scores indicate higher anhedonia
Time Frame
Baseline, 6-month follow-up, 12-month follow-up
Title
Medical Outcome Survey- Short Form
Description
36-item measure of physical and social functioning; score range from 36 to 149; higher scores indicate higher physical and social functioning
Time Frame
Baseline, 6-month follow-up, 12-month follow-up
Title
Quality of Life Enjoyment and Satisfaction Questionnaire
Description
16-item measure of satisfaction and enjoyment across domains (e.g., work, interpersonal); scores range from 16 to 80; higher scores indicate higher life enjoyment and satisfaction
Time Frame
Baseline, 6-month follow-up, 12-month follow-up
Title
Temporal Experience of Pleasure Scale
Description
24-item measure of anticipatory and consummatory pleasure; scores range from 24 to 144; higher scores indicate higher anticipatory/consummatory pleasure
Time Frame
Baseline, 6-month follow-up, 12-month follow-up
Title
Life Events and Difficulties Schedule
Description
Measure of acute events, difficulties, stressors
Time Frame
Baseline, 6-month follow-up, 12-month follow-up
Title
Longitudinal Interval Follow-Up Evaluation (LIFE) (Keller et al., 1987)
Description
Retrospectively assesses different DSM-5 disorders, social and occupational functioning, and life satisfaction over the past 6 months
Time Frame
6-month follow-up, 12-month follow-up
Title
Columbia-Suicide Severity Rating Scale
Description
Suicide assessment
Time Frame
Baseline, 6-month follow-up, 12-month follow-up
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion criteria for MDD/anxiety disorder group:
DSM-5 diagnostic criteria for MDD, Generalized Anxiety Disorder, Social Phobia, Panic Disorder, Post Traumatic Stress (diagnosed using the SCID-5)
Written informed consent
For MDD subjects, a baseline Hamilton Depression Rating Scale score > 16 (17-item version)
Right-handed
Has a smartphone (iPhone or Android) (needed for Ecological Momentary Assessment)
Absence of any psychotropic medications for at least 2 weeks (6 weeks for fluoxetine, 6 months for neuroleptics, 2 weeks for benzodiazepines, 2 weeks for any other antidepressants)
Inclusion criteria for healthy controls:
Absence of medical, neurological, and psychiatric illness (including alcohol and substance abuse), as assessed by subject history and a structured clinical interview (diagnosed using the SCID-5)
Written informed consent
Right-handed
Absence of any medications for at least 3 weeks
Has a smartphone (iPhone or Android) (needed for Ecological Momentary Assessment)
Exclusion criteria for all participants:
Subjects with suicidal ideation where outpatient treatment is determined unsafe by the study clinician
Pregnant women or women of childbearing potential who are not using a medically accepted means of contraception
Serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic or hematologic disease
History of seizure disorder
History or current diagnosis of any of the following DSM-IV psychiatric illnesses: organic mental disorder, schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorders not otherwise specified, bipolar disorder, obsessive-compulsive disorder, patients with mood congruent or mood incongruent psychotic features, substance dependence, substance abuse within the last 12 months (with the exception of cocaine or stimulant abuse; which will lead to exclusion)
History of cocaine or stimulant use (e.g., amphetamine, cocaine, methamphetamine)
History of use of dopaminergic drugs (including methylphenidate)
History or current diagnosis of dementia
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
Failure to meet standard magnetic resonance imaging safety requirements
Abnormal ECG and lab results
History of seizure disorder or currently on anticonvulsants
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jacob Blank, BA
Phone
617-855-4425
Email
jmblank@mclean.harvard.edu
First Name & Middle Initial & Last Name or Official Title & Degree
David Crowley, ALM
Phone
617-855-4432
Email
djcrowley@mclean.harvard.edu
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Through the Conte Center website, we will share de-identified data and tools with the scientific community (e.g., code developed by the Computational Modeling Core). In close collaboration with NIMH, we will develop a certification similar to the "NIMH Data Archive Data Use Certification" currently used by NIMH.
Through the National Database for Clinical Trials Related to Mental Illness, we will share five principal human datasets generated within the Conte Center: (1) Clinical rating scales and self-report scales of affect, mood, symptoms and functioning; (2) Behavioral performance during approach-avoidance tasks; (3) Electrophysiological data; (4) Functional magnetic resonance imaging data; and (5) Hormonal (cortisol) responses.
Through ClinicalTrials.gov, we will share the primary and secondary outcomes.
Learn more about this trial
Pharmaco-Neuroimaging Studies of Approach/Avoidance Behaviors and Post-Mortem Studies: Pharmacological Manipulation
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