Mechanism of Action Underlying Ketamine’s... — Clinical Trial Details

Participants

Ages

18 – 70

Sexes

Male & Female

BMI

Psychosis History

Inclusion Criteria

INCLUSION CRITERIA:
Phases I-II
1. 18 to 70 years of age.
2. Each subject must have understanding sufficient to agree to all required tests and sign informed consent.
3. Subjects must have undergone screening under protocol 01-M-0254 ("The Evaluation of Patients with Mood and Anxiety Disorders and Healthy Volunteers").
4. DSM-IV or DSM-5 diagnosis of Major Depressive Disorder without psychotic features (confirmed by clinical assessment and structured interview, e.g., SCID-P).
5. Initial MADRS ≥ 22 and YMRS < 12 within one week of study entry and upon entry into Phase II.
6. Lack of response to two adequate antidepressant trials (operationalised using ATHF); failed adequate trial of ECT or TMS counts as adequate.
7. Current major depressive episode lasting at least four weeks.
8. Agree to be hospitalised for study participation.

Exclusion Criteria

EXCLUSION CRITERIA (Phases I-II):
1. Current psychotic features or diagnosis of schizophrenia or other psychotic disorder.
2. History of substance abuse/dependence or substance use disorder within preceding 3 months (except caffeine or nicotine); illicit drug use in 2 weeks prior to screening; positive alcohol/drug urine test at screening.
3. Serious unstable medical illnesses (hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, neurologic, immunologic, hematologic).
4. Pregnant or nursing individuals or those able to become pregnant without effective birth control; negative urine pregnancy test prior to drug/imaging.
5. History of seizure (unless clearly resolved) or current use of medications that lower seizure threshold; epilepsy in self or first-degree relatives; stroke, brain surgery, head injury, or known structural brain lesion (excludes TMS procedures).
6. Medical illness likely to alter brain morphology/physiology (e.g., uncontrolled hypertension, diabetes).
7. Clinically significant abnormal laboratory tests.
8. For imaging: evaluated hearing loss that may be worsened by imaging procedures.
9. Positive HIV test.
10. Weight > 119 kg.
11. Treatment with any concomitant psychiatric medication prior to entering Phase II (medications must be tapered during Phase I).
12. Treatment with any non-psychiatric medication(s) that would preclude participation.
13. Any use of opioid medication in the past 3 months.
14. Treatment with a reversible MAOI prior to Phase II (must be tapered in Phase I).
15. Treatment with fluoxetine or aripiprazole at time of screening.
16. Unwilling to stop structured, individualised psychotherapy during Phases I and II (e.g., CBT not permitted).
17. Presence of metallic (ferromagnetic) implants (e.g., pacemaker, aneurysm clip).
18. Claustrophobia or inability to lie supine for up to 90 minutes for MRI/MEG.
19. Subjects judged by investigator to pose current serious suicidal or homicidal risk.
20. History of aggressive behaviour towards others.
21. Current NIMH employee/staff or immediate family member.
Open-Label Ketamine Treatment exclusions include intolerable/serious adverse reaction to ketamine during Phase II; positive urine for illicit substance within 24 hours prior to ketamine; pregnancy or nursing.

Company

Product

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Mechanism of Action Underlying Ketamine’s Antidepressant Effects: The AMPA Throughput Theory in Patients With Treatment-Resistant Major Depression

Detailed Description

Study Protocol

Preparation

Dosing

Locations

Integration

Study Arms & Interventions

Perampanel + ketamine

Interventions

Placebo→Perampanel

Interventions

Placebo + ketamine

Interventions

Participants

Inclusion Criteria

Exclusion Criteria

Study Details

Study Team

Sponsors & Collaborators