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Comparative Effectiveness Research Trial for Antidepressant Incomplete and Non-responders With TRD (ASCERTAINTRD)

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ClinicalTrials.gov Identifier: NCT02977299
Recruitment Status : Recruiting
First Posted : November 30, 2016
Last Update Posted : June 21, 2018
Sponsor:
Collaborator:
Patient-Centered Outcomes Research Institute
Information provided by (Responsible Party):
George I. Papakostas, Massachusetts General Hospital

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 or Duloxetine.

Condition or disease Intervention/treatment Phase
Treatment Resistant Major Depressive Disorder Drug: Aripiprazole Device: Repetitive transcranial magnetic stimulation (rTMS) Drug: Venlafaxine XR Phase 4

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 639 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Augmentation Versus Switch: Comparative Effectiveness Research Trial for Antidepressant Incomplete and Non-responders With Treatment Resistant Depression (ASCERTAIN-TRD)
Actual Study Start Date : May 1, 2017
Estimated Primary Completion Date : October 2021
Estimated Study Completion Date : January 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Antidepressants

Arm Intervention/treatment
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
Oral adjunctive therapy with aripiprazole, dose adjusted for effectiveness and tolerability.
Other Name: 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)
Adjunctive therapy with transcranial magnetic stimulation, dose adjusted for effectiveness and tolerability.

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
Oral switch therapy with venlafaxine, dose adjusted for effectiveness and tolerability.
Other Name: Effexor XR




Primary Outcome Measures :
  1. Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: 8 weeks ]
    Assessment of depression severity.


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


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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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.

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): NCT02977299


Contacts
Contact: Max Martinson 6177242784 mmartinson@partners.org
Contact: George I Papakostas, MD 617-290-4734 gpapakostas@partners.org

Locations
United States, Alabama
The University of Alabama School of Medicine Recruiting
Birmingham, Alabama, United States, 35294
Contact: Richard Shelton, MD       rcshelton@uabmc.edu   
United States, California
Ronald Reagan UCLA Medical Center Not yet recruiting
Los Angeles, California, United States, 90095
Contact: Alexander Bystritsky, M.D.    310-825-9989    abystritsky@mednet.ucla.edu   
Stanford University Recruiting
Stanford, California, United States, 94305
Contact: Charles DeBattista, MD       debattista@stanford.edu   
United States, Georgia
Emory University Terminated
Atlanta, Georgia, United States, 30322
United States, Kansas
Kansas University School of Medicine Recruiting
Wichita, Kansas, United States, 67214
Contact: Matthew Macaluso, DO       mmacaluso@kumc.edu   
United States, Maryland
Shepperd Pratt Health System, University of Maryland School of Medicine Recruiting
Baltimore, Maryland, United States, 21204
Contact: Scott T Aaronson, M.D.    410-938-3000    saaronson@sheppardpratt.org   
United States, Massachusetts
Massachusetts General Hospital, Harvard Medical School Recruiting
Boston, Massachusetts, United States, 02114
Contact: David Mischoulon, MD, PhD    617-724-5198    dmischoulon@partners.org   
United States, New York
New York University Recruiting
New York, New York, United States, 10003
Contact: Dan Iosifescu, MD       Dan.Iosifescu@nyumc.org   
United States, Ohio
Uiversity of Cincinnati Not yet recruiting
Cincinnati, Ohio, United States, 45219
Contact: Erik Nelson, M.D.    513-558-7700    erik.nelson@uc.edu   
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Michael Thase, MD       thase@mail.med.upenn.edu   
United States, South Carolina
Roper St. Francis Hospital Recruiting
Charleston, South Carolina, United States, 29425
Contact: Olga Brawman-Mintzer, M.D.    843-792-1414    mintzero@musc.edu   
United States, Texas
University of Texas Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Contact: Adriane dela Cruz, MD       Adriane.DelaCruz@UTSouthwestern.edu   
Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Contact: Sanjay Mathew, MD       sjmathew@bcm.edu   
United States, Virginia
University of Virginia School of Medicine Terminated
Charlottesville, Virginia, United States, 22908
Canada, British Columbia
University of British Columbia Recruiting
Vancouver, British Columbia, Canada
Contact: Fidel Vila-Rodriguez, M.D.    604-822-7512    fidel.vilarodriguez@ubc.ca   
Canada, Manitoba
University of Manitoba St. Boniface Hospital Recruiting
Winnipeg, Manitoba, Canada, R2H 2A6
Contact: Mandana Modirrousta, M.D.    (204) 237-2606    mmodirrousta@sbgh.mb.ca   
Canada, Ontario
University Health Network Toronto Recruiting
Toronto, Ontario, Canada, M5T 2S8
Contact: Jonathan Downar, M.D.    416-603-5667    jonathan.downar@uhn.ca   
Italy
Foundation Santa Lucia Not yet recruiting
Roma, Italy
Contact: Giacomo Koch, M.D.    +390651501181    g.koch@hsantalucia.it   
Sponsors and Collaborators
Massachusetts General Hospital
Patient-Centered Outcomes Research Institute

Responsible Party: George I. Papakostas, Scientific Director, MGH Clinical Trial Network and Institute (CTNI), Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT02977299     History of Changes
Other Study ID Numbers: 2015P002430
First Posted: November 30, 2016    Key Record Dates
Last Update Posted: June 21, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No

Additional relevant MeSH terms:
Depressive Disorder
Depression
Depressive Disorder, Major
Mood Disorders
Mental Disorders
Behavioral Symptoms
Antidepressive Agents
Venlafaxine Hydrochloride
Aripiprazole
Psychotropic Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Serotonin and Noradrenaline Reuptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Antidepressive Agents, Second-Generation