Longitudinal Observational Biomarker Study (OPT-Neuro)

Neurocognitive and Neuroimaging Biomarkers: Predicting Progression Towards Dementia in Patients With Treatment-resistant Late-life Depression (OPTIMUM-Neuro Study)

The purpose of this study is to test whether treatment-resistant late life depression is associated with declines in memory and attention and brain structure and function.

Study Overview

• Status: Completed
• Conditions: Depression; Dementia; Mild Cognitive Impairment
• Intervention / Treatment: Behavioral: Mechanisms of Late life depression (LLD)-dementia through functional Magnetic Resonance Imaging (fMRI); Behavioral: Neuropsychological Data; Behavioral: Clinical Scales

Detailed Description

The purpose of this study is to test whether treatment-resistant late life depression is associated with declines in memory and attention and brain structure and function. The study will also test if changes in brain structure and function are associated with decreases in memory. In this study, investigators will conduct a series of assessments/tests, mainly brain imaging and assessments of participant's memory and attention, to better understand how depression is linked to memory and thinking in older persons. Investigators hope that their study will help the scientific community to understand why some people with depressive symptoms that are resistant to treatment in late-life experience declines in their memory and attention and whether effective treatment of such depression reduces that risk. Finally, investigators hope that this study will eventually lead to the development of better treatment options.

• Study Type: Observational
• Enrollment (Actual): 506

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M6J 1H1
      • Centre for Addiction and Mental Health
• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Late-Life Mood, Stress, and Wellness Research Program
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine Healthy Mind Lab
  • New York
    • New York, New York, United States, 10032
      • Columbia University Adult and Late Life Depression Clinic
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Late-Life Depression, Evaluation, Prevention, and Treatment Program

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This study will recruit 750 patient across all 5 sites who are 60 years or older with Major Depressive Disorder. All participants will be recruited from the OPTIMUM trial (clinicaltrials.gov identifier NCT02960763); all participants who consent and are eligible to participate in OPTIMUM will be invited to participate in this neuroimaging/neurocognitive study. Eligibility bellow will be determined and assessed as per the OPTIMUM clinical trial. In addition, they will have no contra-indications for MRI scanning.

Description

Inclusion Criteria:

• Men and women aged 60 and older
• Current Major Depressive Disorder (MDD)
• Failure to respond adequately to two or more antidepressant treatment trials of recommended dose and length
• Patient Health Questionnaire-9 (PHQ-9) score of 10 or higher

Exclusion Criteria:

• Dementia
• Lifetime diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms.
• High risk for suicide and unable to be managed safely in the clinical trial
• Non-correctable, clinically significant sensory impairment interfering with participation
• 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
• Seizure disorder.
• Parkinson's Disease
• Individuals with any contraindications to MRI

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Persistent Depression Leading to Change in Cognition	To test whether persistent (non-remitting) depression has the ability to change cognition and lead to greater cognitive decline, and greater degradation of neural circuitry	Baseline, 6-months, 24-months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Neural Circuity	To test whether greater degradation of neural circuitry is associated with greater cognitive decline	Baseline, 6-months, 24-months

Collaborators and Investigators

• Sponsor: Centre for Addiction and Mental Health
• Collaborators: Patient-Centered Outcomes Research Institute; National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Aristotle Voineskos, MD, Centre for Addiction and Mental Health

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2017
• Primary Completion (Actual): July 31, 2024
• Study Completion (Actual): July 31, 2024

Study Registration Dates

• First Submitted: December 24, 2021
• First Submitted That Met QC Criteria: January 21, 2022
• First Posted (Actual): January 24, 2022

Study Record Updates

• Last Update Posted (Estimated): November 25, 2024
• Last Update Submitted That Met QC Criteria: November 22, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Behavioral Symptoms; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction; Depression; Dementia
• Other Study ID Numbers: 080/2017; R01MH114970 (U.S. NIH Grant/Contract); R01MH114980 (U.S. NIH Grant/Contract); R01MH114981 (U.S. NIH Grant/Contract); R01MH114966-01 (U.S. NIH Grant/Contract); R01MH114969 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: A cleaned, complete, and de-identified copy of the final data set including administrative and technical metadata records will be made available on the National Institute of Mental Health (NIMH) Data Archive and registered at clinicaltrials.gov.
• IPD Sharing Time Frame: Data will become available after all analyses and initial publication is complete.
• IPD Sharing 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No