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Optimizing Outcomes of Treatment-Resistant Depression in Older Adults (OPTIMUM)

This study is currently recruiting participants.
Verified August 2017 by Eric Lenze, Washington University School of Medicine
Sponsor:
ClinicalTrials.gov Identifier:
NCT02960763
First Posted: November 10, 2016
Last Update Posted: August 7, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Patient-Centered Outcomes Research Institute
Information provided by (Responsible Party):
Eric Lenze, Washington University School of Medicine
  Purpose
The purpose of this research study is to assess which antidepressants work the best in older adults who have treatment-resistant depression.

Condition Intervention Phase
Treatment Resistant Depression Major Depressive Disorder Drug: Aripiprazole Augmentation Drug: Bupropion Augmentation Drug: Switch to bupropion Drug: Lithium Augmentation Drug: Switch to nortriptyline Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Optimizing Outcomes of Treatment-Resistant Depression in Older Adults

Further study details as provided by Eric Lenze, Washington University School of Medicine:

Primary Outcome Measures:
  • Psychological Well-Being [ Time Frame: 10 weeks (end of Step, and, if applicable, end of Step 2) ]
    Measured by NIH Toolbox Surveys: Positive Affect and General Life Satisfaction

  • Remission from Depression [ Time Frame: 10 weeks (end of Step, and, if applicable, end of Step 2) ]
    Remission defined as Montgomery Asberg Depression Rating Scale score ≤10

  • Serious Adverse Events [ Time Frame: Through study completion (20 weeks, 1 year and 10 weeks, or 1 year and 20 weeks) ]
    Life threatening illness, hospitalization, or need of medical care.


Secondary Outcome Measures:
  • Falls [ Time Frame: 10 weeks (end of Step, and, if applicable, end of Step 2) ]
    Number of falls

  • Fall-related Injuries [ Time Frame: 10 weeks (end of Step, and, if applicable, end of Step 2) ]
    Injuries or impairment resulting from falls

  • Change in executive function [ Time Frame: Baseline, 6 months, 24 months ]
    Measured by composite variable of selected tasks from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Delis-Kaplan Executive Function System (D-KEFS), and NIH Toolbox-Cognition battery.

  • Change in episodic memory [ Time Frame: Baseline, 6 months, 24 months ]
    Measured by composite variable of selected tasks from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Delis-Kaplan Executive Function System (D-KEFS), and NIH Toolbox-Cognition battery.

  • Change in executive-control and cortico-limbic circuitry [ Time Frame: Baseline, 6 months, 24 months ]
    Measured by fMRI

  • Change in plasma biomarkers [ Time Frame: Baseline, 6 months, 24 months ]
    Measured by customized multiplex protein array platform from the Senescence Associated Secretory Protein (SASP) index


Estimated Enrollment: 1500
Actual Study Start Date: February 24, 2017
Estimated Study Completion Date: December 2021
Estimated Primary Completion Date: September 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Aripiprazole Augmentation
Augment current antidepressant treatment with aripiprazole (tablets), titrated from 2-15 mg daily based on symptom severity and side effects.
Drug: Aripiprazole Augmentation
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.
Other Name: Abilify
Experimental: Bupropion Augmentation
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
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.
Other Name: Wellbutrin
Experimental: Switch to Bupropion
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
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.
Other Name: Wellbutrin
Experimental: Lithium Augmentation
Augment current antidepressant treatment with lithium carbonate tablets starting at 300 mg daily, titrated per blood level to 0.4-0.6 meQ/L.
Drug: Lithium Augmentation
Augment current antidepressant treatment with lithium carbonate tablets starting at 300 mg daily, titrated per blood level to 0.4-0.6 meQ/L.
Other Names:
  • Lithium carbonate
  • Eskalith
Experimental: Switch to Nortriptyline
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
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
Other Name: Pamelor,

Detailed Description:

Older adult participants with treatment-resistant depression will be randomly assigned to a Step 1 medication strategy.

  • Adding aripiprazole to current antidepressant medication
  • Adding bupropion to current antidepressant medication
  • Replacing current antidepressant medication with bupropion

If depression is not relieved at the end of 10 weeks, or if participants do not qualify for Step 1, participants will be randomly assigned to a Step 2 medication strategy:

  • Adding lithium to current antidepressant medication
  • Replacing current antidepressant medication with nortriptyline

All medication strategies will be offered in collaboration with participants' own physicians with the the research team providing support and guidance.

After treatment in Step 1 and/or Step 2, participants will enter the Continuation Phase to assess long term follow-up outcomes for 12 months.

Participants in this clinical trial will also be asked to participate in an additional study to gather imaging and biomarker data.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

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 (at least 12 weeks)
  • Patient Health Questionnaire-9 (PHQ-9) score of 6 or higher

Exclusion Criteria:

  • Inability to provide informed consent
  • 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
  • Contraindication to proposed study medications, as determined by study physician including history of intolerance or non-response to proposed medications.
  • 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
  Contacts and Locations
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): NCT02960763


Contacts
Contact: Emily Lenard, MSW 314-747-5706 lenarde@wustl.edu
Contact: Julie Schweiger, CCRC 314-362-3153 schweigj@wustl.edu

Locations
United States, California
UCLA Late-Life Mood, Stress, and Wellness Research Program Recruiting
Los Angeles, California, United States, 90095
Contact: Natalie St. Cyr, MA    310-983-3375    nstcyr@mednet.ucla.edu   
Principal Investigator: Helen Lavretsky, MD         
United States, Missouri
Washington University School of Medicine Healthy Mind Lab Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Emily Lenard, BA    314-747-5706    lenarde@psychiatry.wustl.edu   
Contact: Julie Schweiger, BA    314-362-3153    schweigj@psychiatry.wustl.edu   
Principal Investigator: Eric Lenze, MD         
United States, New York
Columbia University Adult and Late Life Depression Clinic Recruiting
New York, New York, United States, 10032
Contact: Patrick Brown, PhD    646-774-8666    pb2410@cumc.columbia.edu   
Principal Investigator: Steven Roose, MD         
United States, Pennsylvania
UPMC Late-Life Depression, Evaluation, Prevention, and Treatment Program Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Jacqueline Stack, RN, MSN, CNS    412-246-6006    StackJA@upmc.edu   
Principal Investigator: Jordan Karp, MD         
Principal Investigator: Charles F Reynolds III, MD         
Canada, Ontario
Centre for Addiction and Mental Health Recruiting
Toronto, Ontario, Canada, M6J-1H4
Contact: Athina Perivolaris, RN, MN    416-535-8501 ext 32897    athina.perivolaris@camh.ca   
Principal Investigator: Benoit Mulsant, MD         
Sponsors and Collaborators
Washington University School of Medicine
Patient-Centered Outcomes Research Institute
Investigators
Principal Investigator: Eric Lenze, MD Washington University School of Medicine
  More Information

Responsible Party: Eric Lenze, Professor of Psychiatry, Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT02960763     History of Changes
Other Study ID Numbers: TRD-1511-33321
201609085 ( Other Identifier: Washington University Institutional Review Board )
First Submitted: October 28, 2016
First Posted: November 10, 2016
Last Update Posted: August 7, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: A cleaned, complete, and de-identified copy of the final data set including administrative and technical metadata records will be made available through a Washington University in St. Louis (WUSTL) secure repository and registered at clinicaltrials.gov.

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Eric Lenze, Washington University School of Medicine:
Comparative Effectiveness Research
Pragmatic Clinical Trials
Patient-Centered Outcomes Research

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Depressive Disorder, Treatment-Resistant
Behavioral Symptoms
Mood Disorders
Mental Disorders
Antidepressive Agents
Bupropion
Lithium Carbonate
Nortriptyline
Aripiprazole
Psychotropic Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Dopamine Agents
Neurotransmitter Agents
Cytochrome P-450 CYP2D6 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Antimanic Agents
Antidepressive Agents, Tricyclic
Adrenergic Uptake Inhibitors


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