RCT of Brain Longitudinal Biomarker Study (OPT-Neuro RCT)

NCT05531591 | Completed Phase 4 DMC FDA Drug

• 5 other identifiers: 080-2017, 086-2016 RCTR01MH114970R01MH114980R01MH114981R01MH114966-01
• Study Type: interventional
• Target: 87
• Locations: 2 countries
• Sites: 4

Brief Summary

The purpose of this study is to assess which antidepressants work the best in older adults who have treatment-resistant depression (TRD), and to test whether treatment-resistant late life depression is associated with declines in memory and attention and brain structure and function.

Conditions

Depression; Dementia; Mild Cognitive Impairment; Treatment Resistant Depression; Major Depressive Disorder; Treatment-Refractory Depression; Late Life Depression; Geriatric Depression

Keywords

Comparative Effectiveness Research; Pragmatic Clinical Trials; Patient-Centered Outcomes Research; Research Clinical Trial; RCT

Outcome Measures

Primary Outcomes (4)

• Change in Psychological Well-Being

  Psychological well-being was assessed using the NIH Toolbox Psychological Wellbeing subscales of Positive Affect and General Life Satisfaction, with a T score calculated as the average of these two subscales. Higher scores indicate greater positive affect and life satisfaction. Reference T-score (mean=50, Standard Deviation (SD)=10.

  Step 1 (10 weeks), Step 2 (10 weeks), a period of up to 20 weeks

• Assessing the change in the Number of Participants With Remission From Depression

  Remission defined as Montgomery Asberg Depression Rating Scale score ≤10. Scale ranges from 0-60 with higher scores indicating higher depressive symptoms.

  Step 1 (10 weeks), Step 2 (10 weeks), a period of up to 20 weeks

• Safety Outcomes Assessment for Serious Adverse Events

  Assessing; Life threatening illness, hospitalization, or need of medical care over the duration of the study

  Step 1 (10 weeks), Step 2 (10 weeks), a period of up to 20 weeks

• To observe whether persistent (non-remitting) depression leads to greater cognitive decline (focusing on executive and episodic memory (EEM)-related cognitive domains

  Using baseline differences to compare if non-remitters demonstrate greater decline in EEM than remitters leading to greater cognitive decline using . Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).

  Baseline, 6-months, 24-months

Other Outcomes (1)

• Plasma biomarkers will be analyzed using a customized multiplex protein array platform for the Senescence-Associated Secretory Phenotype (SASP).

  Baseline, 6-months, 24-months

Study Arms (5)

Aripiprazole Augmentation

EXPERIMENTAL

Augment current antidepressant treatment with aripiprazole (tablets), titrated from 2-15 mg daily based on symptom severity and side effects.

Drug: Aripiprazole Augmentation

Bupropion Augmentation

EXPERIMENTAL

Augment current antidepressant treatment with bupropion once-daily extended release, titrated from 150-300 mg daily based on symptom severity and side effects.

Drug: Bupropion Augmentation

Switch to Bupropion

EXPERIMENTAL

Taper from current antidepressant therapy. Start bupropion once-daily extended, titrated from 150-300 mg daily based on symptom severity and side effects.

Drug: Switch to bupropion

Lithium Augmentation

EXPERIMENTAL

Augment current antidepressant treatment with lithium carbonate tablets starting at 300 mg daily, titrated per blood level to 0.4-0.6 mEq/L (milliequivalents/liter).

Drug: Lithium Augmentation

Switch to Nortriptyline

EXPERIMENTAL

Taper from current antidepressant therapy. Start on nortriptyline tablets starting at 1 mg per kg of body weight daily, titrated per blood level to 80-120 ng/ml.

Drug: Switch to nortriptyline

Interventions

Aripiprazole Augmentation DRUG

Augment current antidepressant treatment with aripiprazole (tablets). Start at 2 mg daily; increase every two weeks (i.e., to 5, 7, 10 mg) to a maximum of 15 mg daily based on symptom severity and side effects.

Also known as: Abilify

Aripiprazole Augmentation

Bupropion Augmentation DRUG

Augment current antidepressant treatment with bupropion once-daily extended release, starting at 150 mg daily; titrated after four weeks to 300 mg daily based on symptom severity and side effects.

Also known as: Wellbutrin

Bupropion Augmentation

Switch to bupropion DRUG

Taper from current antidepressant therapy. Start bupropion once-daily extended release at 150 mg daily; titrated after four weeks to 300 mg daily based on symptom severity and side effects.

Also known as: Wellbutrin

Switch to Bupropion

Lithium Augmentation DRUG

Augment current antidepressant treatment with lithium carbonate tablets starting at 300 mg daily, titrated per blood level to 0.4-0.6 meQ/L.

Also known as: Lithium carbonate, Eskalith

Lithium Augmentation

Switch to nortriptyline DRUG

Taper from current antidepressant therapy. Start on nortriptyline tablets starting at 1 mg per kg of body weight daily, titrated per blood level to 80-120 ng/ml

Also known as: Pamelor

Switch to Nortriptyline

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women aged 60 and older, with approximately equal proportions aged 60-70 and 70+.
• Current Major Depressive Disorder (MDD), single or recurrent, as diagnosed by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria.
• Failure to respond adequately to two or more antidepressant treatment trials of recommended dose and length (approximately 12 weeks).
• PHQ-9 score of 10 or higher.

You may not qualify if:

• Dementia; patients screened out due to possible dementia will be referred to a local Memory Clinic or back to their clinician for evaluation to clarify the presence or absence of dementia.
• Lifetime diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms.
• High risk for suicide (e.g. active Suicidal ideations (SI) and or current/recent intent or plan)). Urgent psychiatric referral will be made in these cases.
• Non-correctable, clinically significant sensory impairment (e.g., cannot hear well enough to cooperate with interview).
• Unstable medical illness, including delirium, uncontrolled diabetes mellitus, hypertension, hyperlipidemia, or cerebrovascular or cardiovascular risk factors that are not under medical management.
• Moderate to severe substance or alcohol use disorder, as determined by study physician.
• Seizure disorder.
• Parkinson's Disease

Sponsors & Collaborators

• Centre for Addiction and Mental Health: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (4)

UCLA Late-Life Mood, Stress, and Wellness Research Program

Los Angeles, California, 90095, United States

Location

Washington University School of Medicine Healthy Mind Lab

St Louis, Missouri, 63110, United States

Location

Columbia University Adult and Late Life Depression Clinic

New York, New York, 10032, United States

Location

Centre for Addiction and Mental Health

Toronto, Ontario, M6J 1H4, Canada

Location

MeSH Terms

Conditions

Depression; Dementia; Cognitive Dysfunction; Depressive Disorder, Treatment-Resistant; Depressive Disorder, Major

Interventions

Aripiprazole; Bupropion; Lithium Carbonate; Nortriptyline

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders; Depressive Disorder; Mood Disorders

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Propiophenones; Ketones; Organic Chemicals; Carbonates; Alkalies; Inorganic Chemicals; Carbonic Acid; Carbon Compounds, Inorganic; Lithium Compounds; Dibenzocycloheptenes; Benzocycloheptenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• Aristotle Voineskos, MD

  Centre for Addiction and Mental Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2022
• First Posted: September 8, 2022
• Study Start: August 1, 2019
• Primary Completion: July 31, 2024
• Study Completion: July 31, 2024
• Last Updated: November 25, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data will become available after all analyses and initial publication is complete.
• Access Criteria: The data will be accessible through the NIMH Data Archive (Collection ID: 2851). Please contact the principal investigators if you have further queries about access criteria.

Locations

CA (1); US (3)