Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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.
 
ClinicalTrials.gov Identifier: NCT02977299
Recruitment Status : Recruiting
First Posted : November 30, 2016
Last Update Posted : September 2, 2020
Sponsor:
Collaborator:
Patient-Centered Outcomes Research Institute
Information provided by (Responsible Party):
George I. Papakostas, Massachusetts General Hospital

Tracking Information
First Submitted Date  ICMJE November 28, 2016
First Posted Date  ICMJE November 30, 2016
Last Update Posted Date September 2, 2020
Actual Study Start Date  ICMJE May 1, 2017
Estimated Primary Completion Date October 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 28, 2017)
Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: 8 weeks ]
Assessment of depression severity.
Original Primary Outcome Measures  ICMJE
 (submitted: November 29, 2016)
Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: 8 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 28, 2017)
Quality of Life, Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) [ Time Frame: 8 weeks ]
Assessment of quality of life
Original Secondary Outcome Measures  ICMJE
 (submitted: November 29, 2016)
Quality of Life, Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) [ Time Frame: 8 weeks ]
Current Other Pre-specified Outcome Measures
 (submitted: March 28, 2017)
Massachusetts General Hospital Cognitive and Physical Symptoms Questionnaire (MGH CPFQ) [ Time Frame: 8 weeks ]
Assessment of cognitive symptoms
Original Other Pre-specified Outcome Measures
 (submitted: November 29, 2016)
Massachusetts General Hospital Cognitive and Physical Symptoms Questionnaire (MGH CPFQ) [ Time Frame: 8 weeks ]
 
Descriptive Information
Brief Title  ICMJE Comparative Effectiveness Research Trial for Antidepressant Incomplete and Non-responders With TRD
Official Title  ICMJE Augmentation Versus Switch: Comparative Effectiveness Research Trial for Antidepressant Incomplete and Non-responders With Treatment Resistant Depression (ASCERTAIN-TRD)
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Treatment Resistant Major Depressive Disorder
Intervention  ICMJE
  • Drug: Aripiprazole
    Oral adjunctive therapy with aripiprazole, dose adjusted for effectiveness and tolerability.
    Other Name: Abilify
  • Device: Repetitive transcranial magnetic stimulation (rTMS)
    Adjunctive therapy with transcranial magnetic stimulation, dose adjusted for effectiveness and tolerability.
  • Drug: Venlafaxine XR
    Oral switch therapy with venlafaxine, dose adjusted for effectiveness and tolerability.
    Other Name: Effexor XR
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Aripiprazole
  • 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.
    Intervention: 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).
    Intervention: Drug: Venlafaxine XR
Publications * Franck LS, Shellhaas RA, Lemmon M, Sturza J, Soul JS, Chang T, Wusthoff CJ, Chu CJ, Massey SL, Abend NS, Thomas C, Rogers EE, McCulloch CE, Grant K, Grossbauer L, Pawlowski K, Glass HC; Neonatal Seizure Registry study group. Associations between Infant and Parent Characteristics and Measures of Family Well-Being in Neonates with Seizures: A Cohort Study. J Pediatr. 2020 Jun;221:64-71.e4. doi: 10.1016/j.jpeds.2020.02.024.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 29, 2016)
639
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2022
Estimated Primary Completion Date October 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Yury Montas 6177242357 ymontas@partners.org
Contact: George I Papakostas, MD 617-290-4734 gpapakostas@partners.org
Listed Location Countries  ICMJE Canada,   Italy,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02977299
Other Study ID Numbers  ICMJE 2015P002430
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party George I. Papakostas, Massachusetts General Hospital
Study Sponsor  ICMJE Massachusetts General Hospital
Collaborators  ICMJE Patient-Centered Outcomes Research Institute
Investigators  ICMJE Not Provided
PRS Account Massachusetts General Hospital
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP