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Connectivity Affecting the Antidepressant REsponse Study (CAARE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02332291
Recruitment Status : Completed
First Posted : January 6, 2015
Last Update Posted : August 21, 2020
Sponsor:
Information provided by (Responsible Party):
Warren Taylor, Vanderbilt University Medical Center

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.


Condition or disease Intervention/treatment Phase
Major Depressive Disorder Drug: Escitalopram Drug: Bupropion XL Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 160 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Connectivity Affecting the Antidepressant REsponse (The CAARE Study)
Actual Study Start Date : April 2015
Actual Primary Completion Date : August 2020
Actual Study Completion Date : August 2020


Arm Intervention/treatment
Active Comparator: Blinded Escitalopram / Open-Label Bupropion
8 weeks of blinded escitalopram, followed by 8 weeks of open-label bupropion xl for nonremitters
Drug: Escitalopram
Escitalopram 10-20mg daily
Other Name: Lexapro

Drug: Bupropion XL
Bupropion XL 150-450mg daily
Other Name: Wellbutrin XL

Placebo Comparator: Blinded Placebo / Open-Label Bupropion
8 weeks of blinded placebo, followed by 8 weeks of open-label bupropion xl for nonremitters.
Drug: Bupropion XL
Bupropion XL 150-450mg daily
Other Name: Wellbutrin XL




Primary Outcome Measures :
  1. Remission of depression [ Time Frame: up to Week 16 ]
    Montgomery-Asberg Depression Rating Scale (MADRS) is a clinician-rated measure of depression severity. This will be used to define remission as a score of 7 or less


Secondary Outcome Measures :
  1. Change in depression severity, clinician rated [ Time Frame: Baseline to week 8 ]
    Change in depression severity will be measured by the MADRS.

  2. Change in depression severity, self rated [ Time Frame: Baseline to week 8 ]
    Change in depression severity will be measured by the Quick Inventory of Depressive Symptoms, Self-Rated (QIDS-SR16). The QIDS-SR16 is a self-report of depression severity

  3. Change in depression severity, clinician rated [ Time Frame: Week 8 to week 16 ]
    Change in depression severity will be measured by the MADRS.

  4. Change in depression severity, self rated [ Time Frame: Week 8 to week 16 ]
    Change in depression severity will be measured by the Quick Inventory of Depressive Symptoms, Self-Rated (QIDS-SR16).


Other Outcome Measures:
  1. Cerebral hyperintense white matter lesions (MRI) [ Time Frame: Baseline ]
    This is a noninvasive measures of subtle cerebrovascular disease, which can be localized to specific white matter fiber tracts. We will examine pre-treatment measures to determine if they predict subsequent rates of remission as measured by the MADRS

  2. Cerebral hyperintense white matter lesions (MRI) [ Time Frame: Baseline ]
    This is a noninvasive measures of subtle cerebrovascular disease, which can be localized to specific white matter fiber tracts. We will examine pre-treatment measures to determine if they predict subsequent change in depression severity as measured by the MADRS

  3. Cerebral hyperintense white matter lesions (MRI) [ Time Frame: Baseline ]
    This is a noninvasive measures of subtle cerebrovascular disease, which can be localized to specific white matter fiber tracts. We will examine pre-treatment measures to determine if they predict subsequent change in depression severity as measured by the QIDS-SR16



Information from the National Library of Medicine

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Ages Eligible for Study:   60 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  1. Current or past diagnoses of other Axis I psychiatric disorders, except for generalized anxiety disorder (GAD) symptoms occurring during a depressive episode
  2. History of alcohol or drug dependence or abuse in the last three years
  3. History of developmental disorder or IQ score < 70
  4. Presence of acute suicidality
  5. Acute grief (< 1 month)
  6. Current or past psychosis
  7. Primary neurological disorder, including but not limited to dementia, stroke, brain tumors, epilepsy, Parkinson's disease, or demyelinating diseases
  8. MRI contraindications
  9. Any physical or intellectual disability adversely affecting ability to complete assessments
  10. Electroconvulsive therapy in last 6 months
  11. 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.
  12. 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)
  13. Known allergy or hypersensitivity to escitalopram or bupropion
  14. Current or planned psychotherapy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02332291


Locations
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United States, Tennessee
Vanderbilt Psychiatric Hospital
Nashville, Tennessee, United States, 37212
Sponsors and Collaborators
Vanderbilt University Medical Center
Investigators
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Principal Investigator: Warren D Taylor, MD, MHSc Vanderbilt University Medical Center
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Responsible Party: Warren Taylor, Professor of Psychiatry, Vanderbilt University Medical Center
ClinicalTrials.gov Identifier: NCT02332291    
Other Study ID Numbers: 141137
First Posted: January 6, 2015    Key Record Dates
Last Update Posted: August 21, 2020
Last Verified: August 2020
Keywords provided by Warren Taylor, Vanderbilt University Medical Center:
Depression
Geriatrics
Elderly
MRI
Antidepressants
Additional relevant MeSH terms:
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Depressive Disorder
Depressive Disorder, Major
Mood Disorders
Mental Disorders
Citalopram
Bupropion
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Dopamine Uptake Inhibitors
Dopamine Agents
Cytochrome P-450 CYP2D6 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors