Connectivity Affecting the Antidepressant REsponse Study

NCT02332291 | Completed Phase 4 Results

• 1 other identifier: 141137
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 1

Brief Summary

It can be difficult to achieve remission in individuals with late-life depression (LLD) and they often require aggressive treatment. This challenge is in part due to age-related vascular changes that are common in LLD. Successful antidepressant treatment involve changes across affective, cognitive, and default mode networks. We hypothesize that in LLD, vascular disease adversely affects response to antidepressants by disrupting connectivity of these networks. The primary goal of this project is to characterize how focal vascular damage affects regional connectivity and response to antidepressants. Based on past work and pilot data, we a priori focus on the cingulum bundle and uncinate fasciculus. These key fiber bundles connect frontal, temporal, and cingulate regions involved in cognition and affective responses. Our central hypothesis is that ischemic damage to the cingulum bundle and uncinate fasciculus contributes to structural and functional connectivity deficits of those tracts. This results in a disconnection effect that alters the function of connected regions. In turn, this increases the risk of a poor response to antidepressants. Our approach is to enroll up to 130 adults over age 60 years with a diagnosis of Major Depressive Disorder. Subjects will complete clinical evaluation, cognitive testing, and MRI/functional MRI (fMRI) sessions, including an fMRI emotional oddball task that includes attentional and affective components. Participants will be stratified by cerebral lesion severity and randomized in a 2:1 ratio to a double-blinded 8-week trial of escitalopram or matching placebo. Those who do not remit will transition to an 8-week trial of open-label bupropion, an antidepressant with a different mechanism of action. This will allow us to determine if different and distinct circuit deficits affect response to antidepressants with different mechanisms of action while also accounting for the placebo response.

Conditions

Major Depressive Disorder

Keywords

Depression; Geriatrics; Elderly; MRI; Antidepressants

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Remission of Depression

  Montgomery-Asberg Depression Rating Scale (MADRS) is a clinician-rated measure of depression severity. Higher scores indicate greater depression severity, ranging 0-60. This will be used to define remission as a final score of 7 or less

  From Baseline up to Week 16

Secondary Outcomes (4)

• Change in Depression Severity, Clinician Rated

  Baseline to week 8

• Change in Depression Severity, Self Rated

  Baseline to week 8

• Change in Depression Severity, Clinician Rated

  Week 8 to week 16

• Change in Depression Severity, Self Rated

  Week 8 to week 16

Other Outcomes (2)

• Apathy Evaluation Scale (AES)

  Baseline and Week 8

• Ruminative Response Scale (RRS)

  Baseline and Week 8

Study Arms (2)

Blinded Escitalopram / Open-Label Bupropion

ACTIVE COMPARATOR

8 weeks of blinded escitalopram, followed by 8 weeks of open-label bupropion xl for nonremitters

Drug: Escitalopram; Drug: Bupropion XL

Blinded Placebo / Open-Label Bupropion

PLACEBO COMPARATOR

8 weeks of blinded placebo, followed by 8 weeks of open-label bupropion xl for nonremitters.

Drug: Bupropion XL

Interventions

Escitalopram DRUG

Escitalopram 10-20mg daily

Also known as: Lexapro

Blinded Escitalopram / Open-Label Bupropion

Bupropion XL DRUG

Bupropion XL 150-450mg daily

Also known as: Wellbutrin XL

Blinded Escitalopram / Open-Label Bupropion; Blinded Placebo / Open-Label Bupropion

Eligibility Criteria

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

You may qualify if:

• Age 60 years or older.
• Current diagnosis of major depressive disorder (DSM-IV-TR), single episode, recurrent or chronic, without psychotic features, as detected by Mini-International Neuropsychiatric Inventory (MINI) and clinical exam.
• Minimum MADRS score ≥ 15.
• Mini-Mental State Exam ≥ 24.
• Fluent in English.

You may not qualify if:

• Current or past diagnoses of other Axis I psychiatric disorders, except for generalized anxiety disorder (GAD) symptoms occurring during a depressive episode
• History of alcohol or drug dependence or abuse in the last three years
• History of developmental disorder or Intelligence Quotient score \< 70
• Presence of acute suicidality
• Acute grief (\< 1 month)
• Current or past psychosis
• Primary neurological disorder, including but not limited to dementia, stroke, brain tumors, epilepsy, Parkinson's disease, or demyelinating diseases
• MRI contraindications
• Any physical or intellectual disability adversely affecting ability to complete assessments
• Electroconvulsive therapy in last 6 months
• Use of antidepressant medications or other psychotropic medications in the last 4 weeks (or the last 6 weeks for fluoxetine). Occasional use of benzodiazepines or non-benzodiazepine sedatives (such as zolpidem, eszopiclone, or zaleplon) during this period is allowable.
• A failed therapeutic trial of escitalopram in the current depressive episode (defined as at least 6 weeks of treatment at a daily dose of 10mg or higher)
• Known allergy or hypersensitivity to escitalopram or bupropion
• Current or planned psychotherapy

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt Psychiatric Hospital

Nashville, Tennessee, 37212, United States

Location

Related Publications (1)

• Ahmed R, Boyd BD, Elson D, Albert K, Begnoche P, Kang H, Landman BA, Szymkowicz SM, Andrews P, Vega J, Taylor WD. Influences of resting-state intrinsic functional brain connectivity on the antidepressant treatment response in late-life depression. Psychol Med. 2023 Oct;53(13):6261-6270. doi: 10.1017/S0033291722003579. Epub 2022 Dec 9.

  PMID: 36482694 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Interventions

Escitalopram; Bupropion

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Propiophenones; Ketones

Limitations and Caveats

Single-site study; some missing data for self-report other outcome data

Results Point of Contact

• Title: Warren D. Taylor, MD, MHSc
• Organization: Vanderbilt University Medical Center

warren.d.taylor@vumc.org

615-322-1073

Study Officials

• Warren D Taylor, MD, MHSc

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry

Study Record Dates

• First Submitted: December 30, 2014
• First Posted: January 6, 2015
• Study Start: April 1, 2015
• Primary Completion: August 1, 2020
• Study Completion: August 1, 2020
• Last Updated: September 21, 2021
• Results First Posted: September 21, 2021

Record last verified: 2021-08

Locations

US (1)