RECRUITING

Apimostinel + Automated Neurocognitive Training for Depression

Conditions

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

Apimostinel shows initial promise as a novel rapid-acting antidepressant medication with minimal side effects or safety concerns. Cognitive Training (CT) is a digital intervention that has shown promise in extending the durability of another similar drug (ketamine). This randomized controlled trial will test the efficacy and safety of apimostinel (vs. placebo) for the acute treatment of depression, and will test the potential of CT to enhance and/or extend the durability of apimostinel's antidepressant effect.

Official Title

Phase 2, Randomized, Double-Blind, Placebo-Controlled, Single Intravenous Dose, Parallel Efficacy Study of Apimostinel With or Without Subsequent Automated Self-Association Training in Subjects With Major Depressive Disorder

Quick Facts

Study Start:2024-10-28

Study Completion:2029-12-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06400121

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 60 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT

Inclusion Criteria	Exclusion Criteria
1. Participants of any gender are eligible 2. Aged 18 to 60 years 3. Meets Diagnostic and Statistical Manual, Fifth Edition (DSM-V) criteria for major depressive disorder (MDD) 4. MADRS score ≥ 25 at screening 5. Have not responded to one or more adequate trials of FDA-approved antidepressants within the current depressive episode, determined by Antidepressant Treatment History Form (ATHF-SF) criteria \[score ≥ 1\] 6. Score \>1SD above the normative mean on the Cognitive Triad Inventory (CTI) "self" subscale \OR\ \<1SD below the normative mean on the Rosenberg self-esteem scale 7. Participants of childbearing potential with a negative serum pregnancy test prior to entry into the study and who are practicing an adequate method of birth control (eg oral or parenteral contraceptives, intrauterine device, barrier, abstinence) and who do not plan to become pregnant during the course of the study. Participants may be included without a negative serum pregnancy test if they are surgically sterile or at least 2 years post- menopausal. Participants who could impregnate a sexual partner should use an acceptable method of birth control during the study, from the day of dosing to 28 days following dose. 8. Participants who could impregnate a partner and their sexual partner of childbearing potential should use an acceptable method of birth control during the study, from day of dosing to 28 days following dose. 9. Clinical laboratory values \< 1.5 times the upper limit of normal (ULN) or deemed not clinically significant per the investigator 10. Ability to understand the requirements of the study, provide written informed consent, abide by the study restrictions, and agree to return for the required assessments 11. Based on the investigator's clinical judgment, participants with eating disorders, obsessive compulsive disorder (OCD), panic disorder, post-traumatic stress disorder (PTSD), and generalized anxiety disorders secondary to major depressive episodes are permitted.	1. Presence of lifetime bipolar, psychotic, or autism spectrum; or current problematic, moderate-to-severe substance use disorder 2. Use of a Monoamine Oxidase Inhibitor (MAOI) within 28 days of infusion date 3. Huntington's, Parkinson's, Alzheimer's, Multiple Sclerosis, or a history of strokes or with one or more seizures without a clear and resolved etiology 4. Currently hospitalized or residing in an in-patient facility during the study participation 5. Acute suicidality or other psychiatric crises requiring treatment escalation, using the Columbia-Suicide Severity Rating Scale (C-SSRS) as both an initial exclusion criteria (C-SSRS "Baseline/Screening" Version for past 1-month period) and as grounds for rescue/removal (C-SSRS "Since Last Visit" form). Participants with C-SSRS suicide ideation scores scored "yes" on items 4 (active suicidal ideation with some intent to act) and/or 5 (active suicidal ideation with specific plan and intent) will be excluded from the study, and if enrolled, will be exited from the study and referred immediately to the nearest emergency mental health facility for additional thorough assessment and appropriate treatment referral. 6. Changes made to treatment regimen within 28 days of drug infusion (Day 0) 7. Reading level \<6th grade as per patient self-report 8. Serious, unstable medical illnesses including respiratory \[obstructive sleep apnea, or history of difficulty with airway management during previous anesthetics\], cardiovascular \[including ischemic heart disease and uncontrolled hypertension\], and neurologic \[including history of severe head injury diagnoses. 9. Clinically significant abnormal findings of laboratory parameters \[including urine toxicology screen for drugs of abuse\], physical examination, or ECG. 10. Uncontrolled or poorly controlled hypertension, as determined by the study physician's review of vitals collected during screening and any other relevant medical history/records. 11. Patient has clinically significant renal dysfunction as assessed by the estimated glomerular filtration rate \<70 mL/min using the Chronic Kidney Disease Epidemiology Collaboration -creatinine methodology. 12. Patient has liver enzyme test results \>1.5 times the upper limit of normal. 13. Patient has resting heart rate (supine) \<60 or \>100 bpm at the Screening Visit or Pre-Dose Baseline, in the absence of an etiology that, in the judgment of the investigator, is related to exceptionally good cardiovascular fitness. 14. Patient has PR interval \>250 msec at the Screening Visit or Pre-Dose Baseline 15. Patients starting hormonal treatment (e.g., estrogen) in the 3 months prior to Screening. 16. Patients taking medications with known activity at the NMDA or AMPA glutamate receptor \[e.g., riluzole, amantadine, memantine, topiramate, dextromethorphan (including AuvelityTM), D-cycloserine, ketamine or esketamine\], or the mu-opioid receptor. 17. Patients taking any of the following medications: St John's Wort, theophylline, tramadol, metrizamide. 18. Patients who have received ECT in the past 6 months prior to Screening. 19. Patients currently receiving treatment with vagus nerve stimulation (VNS) or repetitive transcranial stimulation (rTMS). 20. Participation in any clinical trial of an investigational product or device within 30 days of enrollment in this trial 21. Positive screen for unreported drugs of abuse, including: cocaine, PCP, opioid or other agent that in the opinion of the investigator is being abused. Positive marijuana screen is not exclusionary if use is consistent with clinical diagnostic interview findings and is seen in the absence of a moderateto-severe substance use disorder. 22. Participants or sexual partners of participants who are currently pregnant or planning to become pregnant during the course of the study 23. Participants who are breastfeeding 24. History of allergy, sensitivity, or intolerance to apimostinel, zelquistinel, NMDAR ligands including ketamine,dextromethorphan, memantine, methadone, dextropropoxyphene, or ketobemidone.

Inclusion Criteria

Exclusion Criteria

1. Participants of any gender are eligible
2. Aged 18 to 60 years
3. Meets Diagnostic and Statistical Manual, Fifth Edition (DSM-V) criteria for major depressive disorder (MDD)
4. MADRS score ≥ 25 at screening
5. Have not responded to one or more adequate trials of FDA-approved antidepressants within the current depressive episode, determined by Antidepressant Treatment History Form (ATHF-SF) criteria \[score ≥ 1\]
6. Score \>1SD above the normative mean on the Cognitive Triad Inventory (CTI) "self" subscale \*OR\* \<1SD below the normative mean on the Rosenberg self-esteem scale
7. Participants of childbearing potential with a negative serum pregnancy test prior to entry into the study and who are practicing an adequate method of birth control (eg oral or parenteral contraceptives, intrauterine device, barrier, abstinence) and who do not plan to become pregnant during the course of the study. Participants may be included without a negative serum pregnancy test if they are surgically sterile or at least 2 years post- menopausal. Participants who could impregnate a sexual partner should use an acceptable method of birth control during the study, from the day of dosing to 28 days following dose.
8. Participants who could impregnate a partner and their sexual partner of childbearing potential should use an acceptable method of birth control during the study, from day of dosing to 28 days following dose.
9. Clinical laboratory values \< 1.5 times the upper limit of normal (ULN) or deemed not clinically significant per the investigator
10. Ability to understand the requirements of the study, provide written informed consent, abide by the study restrictions, and agree to return for the required assessments
11. Based on the investigator's clinical judgment, participants with eating disorders, obsessive compulsive disorder (OCD), panic disorder, post-traumatic stress disorder (PTSD), and generalized anxiety disorders secondary to major depressive episodes are permitted.

1. Presence of lifetime bipolar, psychotic, or autism spectrum; or current problematic, moderate-to-severe substance use disorder
2. Use of a Monoamine Oxidase Inhibitor (MAOI) within 28 days of infusion date
3. Huntington's, Parkinson's, Alzheimer's, Multiple Sclerosis, or a history of strokes or with one or more seizures without a clear and resolved etiology
4. Currently hospitalized or residing in an in-patient facility during the study participation
5. Acute suicidality or other psychiatric crises requiring treatment escalation, using the Columbia-Suicide Severity Rating Scale (C-SSRS) as both an initial exclusion criteria (C-SSRS "Baseline/Screening" Version for past 1-month period) and as grounds for rescue/removal (C-SSRS "Since Last Visit" form). Participants with C-SSRS suicide ideation scores scored "yes" on items 4 (active suicidal ideation with some intent to act) and/or 5 (active suicidal ideation with specific plan and intent) will be excluded from the study, and if enrolled, will be exited from the study and referred immediately to the nearest emergency mental health facility for additional thorough assessment and appropriate treatment referral.
6. Changes made to treatment regimen within 28 days of drug infusion (Day 0)
7. Reading level \<6th grade as per patient self-report
8. Serious, unstable medical illnesses including respiratory \[obstructive sleep apnea, or history of difficulty with airway management during previous anesthetics\], cardiovascular \[including ischemic heart disease and uncontrolled hypertension\], and neurologic \[including history of severe head injury diagnoses.
9. Clinically significant abnormal findings of laboratory parameters \[including urine toxicology screen for drugs of abuse\], physical examination, or ECG.
10. Uncontrolled or poorly controlled hypertension, as determined by the study physician's review of vitals collected during screening and any other relevant medical history/records.
11. Patient has clinically significant renal dysfunction as assessed by the estimated glomerular filtration rate \<70 mL/min using the Chronic Kidney Disease Epidemiology Collaboration -creatinine methodology.
12. Patient has liver enzyme test results \>1.5 times the upper limit of normal.
13. Patient has resting heart rate (supine) \<60 or \>100 bpm at the Screening Visit or Pre-Dose Baseline, in the absence of an etiology that, in the judgment of the investigator, is related to exceptionally good cardiovascular fitness.
14. Patient has PR interval \>250 msec at the Screening Visit or Pre-Dose Baseline
15. Patients starting hormonal treatment (e.g., estrogen) in the 3 months prior to Screening.
16. Patients taking medications with known activity at the NMDA or AMPA glutamate receptor \[e.g., riluzole, amantadine, memantine, topiramate, dextromethorphan (including AuvelityTM), D-cycloserine, ketamine or esketamine\], or the mu-opioid receptor.
17. Patients taking any of the following medications: St John's Wort, theophylline, tramadol, metrizamide.
18. Patients who have received ECT in the past 6 months prior to Screening.
19. Patients currently receiving treatment with vagus nerve stimulation (VNS) or repetitive transcranial stimulation (rTMS).
20. Participation in any clinical trial of an investigational product or device within 30 days of enrollment in this trial
21. Positive screen for unreported drugs of abuse, including: cocaine, PCP, opioid or other agent that in the opinion of the investigator is being abused. Positive marijuana screen is not exclusionary if use is consistent with clinical diagnostic interview findings and is seen in the absence of a moderateto-severe substance use disorder.
22. Participants or sexual partners of participants who are currently pregnant or planning to become pregnant during the course of the study
23. Participants who are breastfeeding
24. History of allergy, sensitivity, or intolerance to apimostinel, zelquistinel, NMDAR ligands including ketamine,dextromethorphan, memantine, methadone, dextropropoxyphene, or ketobemidone.

Contacts and Locations

Study Contact

Rebecca B Price, PhD

CONTACT

4123832150

canlab@pitt.edu

Crystal Spotts, M.Ed.

CONTACT

412-246-5764

spottscr@upmc.edu

Principal Investigator

Rebecca B Price, PhD

PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Study Locations (Sites)

Western Psychiatric Institute and Clinic

Pittsburgh, Pennsylvania, 15213

United States

Collaborators and Investigators

Sponsor: Rebecca Price

Rebecca B Price, PhD, PRINCIPAL_INVESTIGATOR, University of Pittsburgh

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-10-28

Study Completion Date2029-12-01

Study Record Updates

Study Start Date2024-10-28

Study Completion Date2029-12-01

Terms related to this study

Additional Relevant MeSH Terms

Depression