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Sustaining Remission of Psychotic Depression (STOP-PD)

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ClinicalTrials.gov Identifier: NCT01427608
Recruitment Status : Completed
First Posted : September 1, 2011
Results First Posted : March 5, 2019
Last Update Posted : March 5, 2019
Sponsor:
Collaborators:
University of Toronto
University of Massachusetts, Worcester
University of Pittsburgh
Information provided by (Responsible Party):
Weill Medical College of Cornell University

Tracking Information
First Submitted Date  ICMJE August 30, 2011
First Posted Date  ICMJE September 1, 2011
Results First Submitted Date  ICMJE December 17, 2018
Results First Posted Date  ICMJE March 5, 2019
Last Update Posted Date March 5, 2019
Study Start Date  ICMJE October 2011
Actual Primary Completion Date November 30, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 13, 2019)
Number of Subjects at Risk of Relapse During the Randomized Phase. [ Time Frame: From entry into randomized phase (baseline) and 36 weeks or earlier relapse ]
Relapse criteria include at least one of the following: 1)Structured Clinical Interview for Diagnostic Statistical Manual #4 Trade Revision (DSM-IV-TR) Axis 1 Disorders (SCID) symptoms of major depression maintained over two weeks 2)17-item Hamilton Depression Rating Scale score of >17 maintained for more than one week + a mean increase of 5 points from entry into randomized phase 3)Re-emergence of psychosis for more than one week, with a SADS (Schedule for Affective Disorders and Schizophrenia) score of >2 on delusion or hallucination severity items 4)Significant clinical worsening defined as either emergence of high-risk of suicide, and/or development of mania for greater than one week, and/or psychiatric hospitalization.
Original Primary Outcome Measures  ICMJE
 (submitted: August 31, 2011)
Risk of relapse during the randomized phase. [ Time Frame: From entry into randomized phase until 36 weeks or earlier relapse ]
Relapse criteria include at least one of the following: 1)SCID symptoms of major depressive episode maintained over two weeks 2)17-item HAM-D score of >17 maintained for more than one week + a mean increase of 5 points from entry into randomized phase 3)Re-emergence of SCID defined psychosis for more than one week, with a score of >2 on SADS delusion or hallucination severity items 4)Significant clinical worsening defined as either emergence of high-risk of suicide, and/or development of mania for greater than one week, and/or psychiatric hospitalization.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 13, 2019)
  • Changes in Metabolic Measures: Weight [ Time Frame: From entry into randomized phase (baseline) and 36 weeks ]
    Change in weight from entry into randomized phase (baseline) and 36 weeks.
  • Changes in Metabolic Measure: Cholesterol [ Time Frame: From entry into randomized phase (baseline) and 36 weeks ]
    Change in cholesterol from entry into randomized phase (baseline) and 36 weeks.
  • Changes in Metabolic Measures: Triglycerides [ Time Frame: From entry into randomized phase (baseline) and 36 weeks ]
    Change in triglycerides from entry into randomized phase (baseline) and 36 weeks.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 31, 2011)
Changes in metabolic measures [ Time Frame: From entry into randomized phase until up to 36 weeks later ]
Weight and clinical laboratory analyses of cholesterol and triglycerides
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Sustaining Remission of Psychotic Depression
Official Title  ICMJE Sustaining Remission of Psychotic Depression
Brief Summary

The acute phase of this study will monitor the response to a combination of an atypical antipsychotic medication olanzapine with an antidepressant medication sertraline in the acute treatment of the disorder. It is predicted that this combination will improve symptoms of psychotic depression and be associated metabolic side effects. Factors that moderate tolerability will be monitored. Improvement in symptoms could take between 4 and 12 weeks, followed by a period of 8 weeks during which participants will continue to take the same medications to stabilize the remission from symptoms of psychotic depression.

The maintenance phase will be a randomized, double-blind, placebo-controlled study of olanzapine for a period of up to 36 weeks to test whether continuing this combination decreases the risk of relapse and whether discontinuing the combination leads to improvement in metabolic measures. Subjects who complete the acute phase will be asked to consent separately to the randomized maintenance phase.

Detailed Description The original STOP-PD study established that the combination of olanzapine and sertraline was significantly better than olanzapine alone in achieving remission of psychotic depression. This STOP-PD-II Sustaining Remission study aims to assess the long-term tolerability of taking this combination of medications and their efficacy at preventing a relapse of the symptoms. The acute phase of the study will monitor the efficacy and tolerability of the olanzapine and sertraline combination, including investigation of weight and metabolic variables, age effects on treatment response and tolerability, and the association of genetic polymorphisms to response or relapse. When subjects are stabilized on these medications for a period of 8 weeks they will be invited to participate in the randomized phase of the research: the olanzapine will be placebo-controlled, meaning half of the subjects will continue to take the olanzapine/sertraline combination and half will take a sertraline/placebo combination, for a period of 36 weeks. Symptoms and side effects will be monitored regularly throughout this phase. Randomization will be stratified on a 1:1 basis by age 60 and above.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Psychotic Depression
Intervention  ICMJE
  • Drug: Sertraline + Olanzapine
    Olanzapine 15mg/day. Adjustment of dose to 5mg/day to a maximum of 20mg/day will be permitted if necessitated by significant side-effects or clinical worsening
    Other Name: Zyprexa
  • Drug: Sertraline + Placebo
    Taper from current dose of olanzapine to placebo over 4 weeks. Continue placebo for remainder of 36 week study.
    Other Name: Placebo
Study Arms  ICMJE
  • Active Comparator: Sertraline + Olanzapine
    Randomized to continue with sertraline and olanzapine under double-blind conditions.
    Intervention: Drug: Sertraline + Olanzapine
  • Placebo Comparator: Sertraline + Placebo
    Randomized to continue with sertraline and substitute placebo for olanzapine under double-blind conditions.
    Intervention: Drug: Sertraline + Placebo
Publications *

*   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 Completed
Actual Enrollment  ICMJE
 (submitted: June 8, 2017)
269
Original Estimated Enrollment  ICMJE
 (submitted: August 31, 2011)
392
Actual Study Completion Date  ICMJE November 30, 2017
Actual Primary Completion Date November 30, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Aged 18-85 years, inclusive
  2. Diagnosis: Diagnostic Statistical Manual-IV Trade Revision (DSM IV-TR) non-bipolar major depression with psychotic features established by both clinical interview with research psychiatrist and administration of SCID-IV.
  3. Score >2 on Schedule for Affective Disorders (SADS) delusion severity item
  4. Score >1 on any of the three conviction items of the Delusion Assessment Scale (DAS) (does not alter belief in response to reality testing)
  5. 17-item HAM-D score of >20

Exclusion Criteria:

  1. Current or lifetime DSM-IV-TR history of schizophrenia or other psychotic disorders or meeting current criteria for brief psychotic disorder, body dysmorphic disorder or obsessive-compulsive disorder
  2. Current or lifetime DSM-IV-TR bipolar affective disorder
  3. History of DSM-IV-TR defined alcohol or substance abuse or dependence within the past three months
  4. Dementia or clinically significant cognitive impairment prior to index episode of depression, and/or a mean score >3 on 26-item caregiver assessment
  5. Type 1 diabetes mellitus (defined as insulin-dependent diabetes mellitus with onset before age 35, and/or diabetes mellitus complicated by prior documented episode of ketoacidosis
  6. Acute or unstable medical illness within the past 3 months; current abnormal serum free T4; current abnormally low vitamin B4 or folic acid level; medical conditions and/or medications for which psychotic or depressive symptoms can be a direct manifestation; neurological disease associated with extrapyramidal signs and symptoms; epilepsy, if the person has had one or more grand mal seizures within the past 12 months.
  7. The need for treatment with any psychotropic medication other than sertraline, olanzapine or lorazepam; or with an anticonvulsant medication with mood-stabilizing properties.
  8. Current pregnancy or plan to become pregnant during the course of the study; breast feeding in women with infants.
  9. A documented history of being unable to tolerate olanzapine or sertraline including significant bradycardia (heart rate of <50 bpm), and serum sodium level of 129mmol/L or below.
  10. History of non-response of the index episode of psychotic depression to at least a 6-week trial of at least 150mg/day sertraline combined with 15mg/day olanzapine
  11. Patients showing ongoing improvement in current episode of psychotic depression with treatment other than sertraline or olanzapine
  12. Patients who are in immediate need of electroconvulsive therapy (ECT) (imminent risk of suicide, refusing to eat, catatonic)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01427608
Other Study ID Numbers  ICMJE STOP-PD-II
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Weill Medical College of Cornell University
Study Sponsor  ICMJE Weill Medical College of Cornell University
Collaborators  ICMJE
  • University of Toronto
  • University of Massachusetts, Worcester
  • University of Pittsburgh
Investigators  ICMJE
Principal Investigator: George Alexopoulos, MD Weill Medical College of Cornell University
Principal Investigator: Alastair Flint, MD University of Toronto
Principal Investigator: Anthony Rothschild, MD University of Massachusetts, Worcester
Principal Investigator: Ellen Whyte, MD University of Pittsburgh
PRS Account Weill Medical College of Cornell University
Verification Date February 2019

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