Nociceptin receptor blockade to change approach and avoidance behavior in depression and anxiety.
Pharmaco-Neuroimaging Studies of Approach/Avoidance Behaviors and Post-Mortem Studies: Study 1.1. (Pharmacological Manipulation)
This trial will test whether a drug that blocks the nociceptin receptor can normalize brain signals and help unmedicated adults with major depression or anxiety make more balanced approach/avoidance decisions.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 112 (estimated) |
| Ages | 18 Years to 45 Years |
| Sex | All |
| Sponsor | Mclean Hospital Academic / other |
| Locations | 1 site (Belmont, Massachusetts) |
| Trial ID | NCT05232032 on ClinicalTrials.gov |
What this trial studies
This Phase 2, pharmaco-neuroimaging study gives a nociceptin receptor antagonist to unmedicated adults with major depressive disorder or anxiety disorders and compares them with healthy controls. Participants complete neuroimaging while performing approach/avoidance decision tasks and are exposed to aversive stimuli to probe corticostriatal-midbrain circuitry function. The protocol includes smartphone-based ecological momentary assessment to track real-world symptoms and behavior between visits. The primary aim is to see if blocking the nociceptin receptor normalizes neural circuitry and behavioral responses linked to avoidance.
Who should consider this trial
Good fit: Unmedicated, right-handed adults who meet DSM-5 criteria for major depressive disorder or specified anxiety disorders (with HAM-D > 16 for MDD), can complete required medication washouts, and can use a smartphone for ecological momentary assessment are ideal candidates.
Not a fit: People who are currently taking psychotropic medications without completing the required washout, have medical or neurological exclusions, are non–right-handed, or cannot travel to the Belmont, MA site or use a smartphone are unlikely to benefit or qualify.
Why it matters
Potential benefit: If successful, this could lead to a new treatment that reduces avoidance and improves decision-making and mood symptoms in people with depression or anxiety.
How similar studies have performed: Preclinical work and some early human studies indicate that modulating the nociceptin/NOPR system can alter stress and mood-related circuits, but clinical efficacy for depression or anxiety remains limited and exploratory.
Eligibility criteria
Show full inclusion / exclusion 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
Where this trial is running
Belmont, Massachusetts
- Mclean Hospital — Belmont, Massachusetts, United States (Recruiting)
Study contacts
- Principal investigator: Diego Pizzagalli, Ph.D. — Mclean Hospital
- Study coordinator: Ethan M Zhang, BA
- Email: ezhang24@mclean.harvard.edu
- Phone: 617-855-4434
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.