Clinical trial NCT02977299: Comparative Effectiveness Research Trial for Antidepressant Incomplete and Non-responders With TRD
Official title: Augmentation Versus Switch: Comparative Effectiveness Research Trial for Antidepressant Incomplete and Non-responders With Treatment Resistant Depression (ASCERTAIN-TRD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Treatment Resistant Major Depressive Disorder
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Patient-Centered Outcomes Research Institute
First posted: 2016-11-30
Enrollment: 278
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: 8 weeks
Secondary outcomes:
measure: Quality of Life, Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF)
timeFrame: 8 weeks
Other outcomes:
measure: Massachusetts General Hospital Cognitive and Physical Symptoms Questionnaire (MGH CPFQ)
timeFrame: 8 weeks
Locations:
city: Birmingham
country: United States
facility: The University of Alabama School of Medicine
state: Alabama
city: Los Angeles
country: United States
facility: Pacific Institute of Medical Research
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Chicago
country: United States
facility: Northwestern University, Feinberg School of Medicine
state: Illinois
city: New York
country: United States
facility: New York University
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Charleston
country: United States
facility: Roper St. Francis Hospital
state: South Carolina
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Vancouver
country: Canada
facility: University of British Columbia
state: British Columbia
city: Winnipeg
country: Canada
facility: University of Manitoba St. Boniface Hospital
state: Manitoba
Study officials:
References: