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History of Changes for Study: NCT02977299
Comparative Effectiveness Research Trial for Antidepressant Incomplete and Non-responders With Treatment Resistant Depression (ASCERTAIN-TRD)
Latest version (submitted April 26, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 November 29, 2016 None (earliest Version on record)
2 February 1, 2017 Contacts/Locations, Study Status, Conditions and Study Identification
3 March 28, 2017 Study Status, Outcome Measures, Study Design, Oversight, IPDSharing and Arms and Interventions
4 May 18, 2017 Recruitment Status, Study Status, Contacts/Locations, Study Identification and Oversight
5 May 19, 2017 Contacts/Locations and Study Status
6 June 2, 2017 Contacts/Locations and Study Status
7 July 26, 2017 Study Status and Contacts/Locations
8 August 29, 2017 Study Status and Contacts/Locations
9 September 25, 2017 Contacts/Locations and Study Status
10 February 16, 2018 Contacts/Locations, Study Status and Study Description
11 March 26, 2018 Contacts/Locations and Study Status
12 April 10, 2018 Study Status and Contacts/Locations
13 April 23, 2018 Contacts/Locations and Study Status
14 June 7, 2018 Contacts/Locations and Study Status
15 June 20, 2018 Contacts/Locations and Study Status
16 December 7, 2018 Contacts/Locations and Study Status
17 March 21, 2019 Contacts/Locations and Study Status
18 August 31, 2020 Contacts/Locations and Study Status
19 April 26, 2022 Recruitment Status, Study Status, Contacts/Locations and Study Design
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Study NCT02977299
Submitted Date:  November 29, 2016 (v1)

Open or close this module Study Identification
Unique Protocol ID: pending2016
Brief Title: Comparative Effectiveness Research Trial for Antidepressant Incomplete and Non-responders With Treatment Resistant Depression (ASCERTAIN-TRD)
Official Title: Augmentation Versus Switch: Comparative Effectiveness Research Trial for Antidepressant Incomplete and Non-responders With Treatment Resistant Depression (ASCERTAIN-TRD)
Secondary IDs:
Open or close this module Study Status
Record Verification: November 2016
Overall Status: Not yet recruiting
Study Start: November 2016
Primary Completion: October 2021 [Anticipated]
Study Completion: January 2022 [Anticipated]
First Submitted: November 28, 2016
First Submitted that
Met QC Criteria:
November 29, 2016
First Posted: November 30, 2016 [Estimate]
Last Update Submitted that
Met QC Criteria:
November 29, 2016
Last Update Posted: November 30, 2016 [Estimate]
Open or close this module Sponsor/Collaborators
Sponsor: Massachusetts General Hospital
Responsible Party: Principal Investigator
Investigator: George I. Papakostas
Official Title: Scientific Director, MGH Clinical Trial Network and Institute (CTNI)
Affiliation: Massachusetts General Hospital
Collaborators: Patient-Centered Outcomes Research Institute
Open or close this module Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary: This is a multi-site, randomized, open-label, effectiveness trial comparing three treatment arms for Major Depressive Disorder (MDD) patients with TRD who are currently on ongoing, stable and adequate antidepressant therapy (ADT). Adequate ADT is defined as a therapeutically sufficient dose for a sufficient treatment period, which would be expected to be effective as listed in the MGH Antidepressant Treatment Response Questionnaire (ATRQ). Patients will be randomized in a 1:1:1 fashion to one of three open-label treatment arms: a) aripiprazole augmentation, b) rTMS augmentation, and c) switching to venlafaxine XR.
Detailed Description:
Open or close this module Conditions
Conditions: Treatment Resistant Major Depressive Disorder Depression
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Parallel Assignment
Number of Arms: 3
Masking: None (Open Label)
Allocation: Randomized
Enrollment: 639 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Aripiprazole Augmentation
Patients randomized to this treatment arm will be instructed to continue all permitted psychotropics at their current dose throughout the 8-week trial and initiate adjunctive aripiprazole. The starting dose will be 5mg daily. The dose may be reduced to as low as 2mg for tolerability issues (this will be the lowest dose permitted for continuation in the trial). The dose may be adjusted in 2 or 5mg increments. The minimum time per increment will be 7 days. The maximum dose will be set at 15mg daily. For patients who are not on potent cytochrome 2D6 inhibitors (such as paroxetine, fluoxetine, duloxetine) or on potent cytochrome 3A4 inhibitors (such as fluvoxamine and nefazodone) and who are able to tolerate 15mg daily, the maximum dose can be raised to 20mg daily for efficacy.
Drug: Aripiprazole
Other Names:
  • Abilify
Experimental: rTMS Augmentation
Patients randomized to this treatment arm will be instructed to continue all permitted psychotropics at their current dose throughout the 8-week trial. We will use clinical TMS stimulators with focal figure-of-eight coils. We will start by measuring the patient´s motor threshold (MT), which is a measure of cortical excitability used to standardize the intensity of stimulation across subjects.
Device: Repetitive transcranial magnetic stimulation (rTMS)
Experimental: Switching To Venlafaxine XR
Patients randomized to this treatment arm will be instructed to continue all permitted psychotropics throughout the 8-week trial, except for their antidepressant(s). They will be instructed to discontinue all antidepressants and initiate venlafaxine that day, as direct switch to serotonergic antidepressants is well tolerated and avoids loss of precious therapeutic time (Montgomery et al., 2014), including to switching to venlafaxine in STAR*D (Rush et al., 2006b). For patients who do not prefer a direct switch, or when clinically indicated otherwise in the opinion of the site investigator, a gradual tapering during the screening period will be permitted as long as a direct switch to venlafaxine is made on the baseline visit from the final antidepressant dose. The starting dose of venlafaxine will be 75mg daily. The dose may be reduced to as low as 37.5mg for tolerability issues (this will be the lowest dose permitted for continuation in the trial).
Drug: Venlafaxine XR
Other Names:
  • Effexor XR
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Montgomery-Asberg Depression Rating Scale (MADRS)
[ Time Frame: 8 weeks ]

Secondary Outcome Measures:
1. Quality of Life, Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF)
[ Time Frame: 8 weeks ]

Other Outcome Measures:
1. Massachusetts General Hospital Cognitive and Physical Symptoms Questionnaire (MGH CPFQ)
[ Time Frame: 8 weeks ]

Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age: 80 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  1. women and men ages 18-80,
  2. with MDD, of at least 12 weeks duration, according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria confirmed by the Mini International Neuropsychiatric Interview (MINI; Sheehan et al, 1998),
  3. have a Montgomery-Asberg Depression Rating Scale (MADRS - Montgomery and Asberg, 1979) score of at least 20 at screen and baseline as assessed by site clinicians,
  4. meet criteria for TRD during the current major depressive episode documented in the MGH Antidepressant Treatment History Questionnaire (ATRQ) (Chandler et al., 2010), which will be defined as being non-responders (less than 50% of symptom improvement) to two or more depression treatment trials of adequate dose and duration as defined by the MGH ATRQ,
  5. are currently on an antidepressant of adequate dose (as defined by the MGH ATRQ) and duration (at least 8 weeks), with the antidepressant dose being stable over the past four weeks, and with documented (in the MGH ATRQ) non-response (less than 50% improvement) to the current antidepressant.
  6. Patients who have passed the MGH CTNI remote assessment, with documentation provided to sites by MGH CTNI.

Exclusion Criteria:

  1. pregnant or breastfeeding women, women of childbearing potential who are not using an accepted means of birth control, or women with a positive urine pregnancy test,
  2. patients who have received treatment with rTMS, aripiprazole, electroconvulsive therapy (ECT), or venlafaxine during the current episode,
  3. patients who express an objection to receiving treatment with at least one of the three treatment arms of our study,
  4. patients with any history of bipolar disorder or psychosis (diagnosed by MINI),
  5. patients with active alcohol or substance abuse disorders within the past 6 months (diagnosed by MINI),
  6. patients with suicidal ideation of the degree that, in the opinion of the evaluating clinician, participation in the study would place them at significantly increased risk of suicide,
  7. patients with unstable medical issues of such degree that, in the opinion of the evaluating clinician, participation in the study would place them at significant risk of a serious adverse event, or patients with a screening hemoglobin A1c level greater than 7.5%, or patients with epilepsy, dementia, Parkinson's disease, or Huntington's Disease,
  8. patients who have received treatment with vagus nerve stimulation (VNS),
  9. patients who have not responded to more than five FDA-approved antidepressant treatment trials of adequate dose and duration during the current episode, or who did not respond to ECT in previous episodes
  10. patients on excluded medications,
  11. patients with a positive urine screen drug test for a substance for which they do not have a valid prescription for a valid medical reason,
  12. patients with currently abnormal thyroid function tests,
  13. patients who have received at least one dose of a monoamine oxidase inhibitor (MAOI) four weeks or less prior, and
  14. for patients on concomitant psychotropic agents (anticonvulsants, benzodiazepines, hypnotics, opiates, triiodothyronine (T3), modafinil, psychostimulants, buspirone, melatonin, omega-3 fatty acids, folate, l-methylfolate, s-adenosyl methionine, lithium) not on the same dose for at least four weeks prior to study entry or who do not agree to continue at the same dose during the acute phase of the study.
  15. Patients who do not meet safety criteria for TMS: history of seizures, cardiac pacemaker, DBS or VNS, brain aneurism clips or other metallic implants in the intracranial space.
  16. Also excluded is an individual who has received any administration of ketamine in the current episode for the treatment of depression.
Open or close this module Contacts/Locations
Central Contact Person: Max Martinson
Telephone: 6177242784
Email: mmartinson@partners.org
Central Contact Backup: George I Papakostas, MD
Telephone: 617-290-4734
Email: gpapakostas@partners.org
Locations: United States, Alabama
The University of Alabama School of Medicine
Birmingham, Alabama, United States, 35294
Contact:Contact: Richard Shelton, MD rcshelton@uabmc.edu
United States, California
Stanford University
Stanford, California, United States, 94305
Contact:Contact: Charles DeBattista, MD debattista@stanford.edu
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
Contact:Contact: John Zajecka, MD john_zajecka@rush.edu
United States, Kansas
Kansas University School of Medicine
Wichita, Kansas, United States, 67214
Contact:Contact: Matthew Macaluso, DO mmacaluso@kumc.edu
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Contact:Contact: David Mischoulon, MD, PhD 617-724-5198 dmischoulon@partners.org
United States, New York
Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10029
Contact:Contact: Dan Iosifescu, MD dan.iosifescu@exchange.mssm.edu
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Contact:Contact: Michael Thase, MD thase@mail.med.upenn.edu
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
Baylor College of Medicine
Houston, Texas, United States, 77030
Contact:Contact: John Zajecka, MD john_zajecka@rush.edu
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Citations:
Links:
Available IPD/Information:

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