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Project to Improve Symptoms and Mood in People With Spinal Cord Injury (PRISMS)

Primary Purpose

Major Depressive Disorder, Dysthymia, Spinal Cord Injuries

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
venlafaxine XR
placebo
Sponsored by
University of Washington
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Major Depressive Disorder focused on measuring spinal cord injuries, major depressive disorder, dysthymia, antidepressant agents, pain, quality of life, muscle spasticity, community participation, anxiety

Eligibility Criteria

18 Years - 64 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Spinal cord injury (ASIA A-D)
  • At least one month post injury
  • Meets DSM IV criteria for major depression or dysthymia on the SCID
  • At least moderately severe depression (PHQ-9 score >= 10)
  • Within reasonable travel distance to one of the study sites

Exclusion Criteria:

  • Current DSM IV alcohol or drug dependence
  • History of bipolar disorder or psychosis
  • History of >= 2 suicide attempts or suicide attempt with 5 years
  • Current suicidal intent or plan
  • Medical contraindications
  • Non-English speaker
  • Clinically significant cognitive/language impairment
  • History of allergic reaction to venlafaxine XR or use of MAO-I with 2 weeks
  • Current use of antidepressant medications (will not exclude if on low dose of a tricyclic antidepressant or trazodone for pain, sleep, or bladder), psychotherapy for depression, or electroconvulsive therapy
  • Pregnant or lactating women or women of childbearing potential who are not willing to use a reliable form of contraception
  • Unstable medical condition, as determined by physical examination, CBC w/ platelets (including hematocrit, hemoglobin, WBC, differential), serum chemistry panel (serum sodium, potassium, chloride, bicarbonate, BUN, creatinine, glucose), liver transaminases (AST, ALT), thyroid stimulating hormone (TSH), urinalysis, supine diastolic blood pressure (SDBP) > 90 mm Hg, or near terminal illness (primary care physician estimates that patient has < 1 year to live)
  • Anticipated major surgical procedures within the 12 weeks of randomization
  • Use of an investigational drug within 30 days
  • Use of psychoactive medications, including corticosteroids and anticonvulsants, that have not been at a stable dose for at least 2 weeks
  • Use of anxiolytic, sedative-hypnotic, or other psychotropic drug or substance (including St. John's Wort) within 7 days of start of double-blind treatment. If the patient is taking a sedative deemed necessary for sleep induction or spasticity, the dosage must have been stable for at least 2 weeks. Use of anticholinergic, low-dose tricyclic antidepressant, GABAergic or adrenergic medications for spasticity are permitted if at a stable dose for at least 2 weeks.
  • Refusal to participate

Sites / Locations

  • University of Alabama
  • University of Miami
  • Rehabilitation Institute of Chicago
  • University of Michigan
  • Baylor Institute for Rehabilitation
  • University of Washington/Harborview Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

placebo

venlafaxine XR

Arm Description

identically encapsulated placebo pills 37.5 - 300 mg/day for 12 weeks

venlafaxine XR 37.5 - 300 mg/day for 12 weeks

Outcomes

Primary Outcome Measures

Hamilton Depression Rating Scale-17
The 17-item Hamilton Depression Rating Scale is a clinician rated measure of depression severity (we used a structured interview version (Williams 1988) to improve inter-rater reliability). Scores range from 0-52. Higher scores indicate more severe depression. Scores of 7 or less indicate remission from depression.
Hamilton Depression Rating Scale-Maier Subscale
The Maier is a 6-item sub scale of the Hamilton derived from Rasch analysis. It is a unidimensional scale with superior sensitivity to change. It excludes somatic items and is therefore especially appropriate for individuals who have substantial physical impairment and medical comorbidity. Scores can range from 0-22 with higher scores indicating more severe depression. Scores of 4 or less indicated in remission from depression.

Secondary Outcome Measures

Symptom Checklist-20 Depression Subscale
Modified Brief Pain Inventory
Modified Ashworth Spasticity Scale
Structured Clinical Interview for DSM IV Depression Module
SF-12
Side Effects Checklist
Craig Handicap and Reporting Technique
Satisfaction With Life
Sheehan Disability Scale
Clinical Global Impression
Patient Global Impression
Hamilton Rating Scale for Anxiety

Full Information

First Posted
January 1, 2008
Last Updated
December 31, 2014
Sponsor
University of Washington
Collaborators
University of Michigan, Shirley Ryan AbilityLab, University of Alabama at Birmingham, Baylor Health Care System, University of Miami, New York University
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1. Study Identification

Unique Protocol Identification Number
NCT00592384
Brief Title
Project to Improve Symptoms and Mood in People With Spinal Cord Injury
Acronym
PRISMS
Official Title
A Controlled Trial of Venlafaxine XR for Major Depression After Spinal Cord Injury: A Multi-site Study
Study Type
Interventional

2. Study Status

Record Verification Date
December 2014
Overall Recruitment Status
Completed
Study Start Date
July 2007 (undefined)
Primary Completion Date
September 2012 (Actual)
Study Completion Date
September 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Washington
Collaborators
University of Michigan, Shirley Ryan AbilityLab, University of Alabama at Birmingham, Baylor Health Care System, University of Miami, New York University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Depression is likely the most prevalent and disabling psychological complication associated with spinal cord injury (SCI). Yet no controlled depression treatment trials have been performed in this population. The proposed study is a multi-site, randomized, double-blind, placebo controlled trial of venlafaxine XR (Effexor XR) in 133 adults with SCI and major depressive disorder (MDD) or dysthymia who are at least one month post injury. Participants will be recruited from four SCI Model System sites, the University of Washington, Rehabilitation Institute of Chicago, University of Michigan, University of Alabama, Birmingham and Baylor Institute for Rehabilitation, Dallas, TX. The purpose of the study is to examine the efficacy and tolerability of venlafaxine XR as a treatment for MDD. The primary outcome will be the percent of responders (those who report at least a 50% reduction in depression severity from baseline to the end of treatment) in the venlafaxine XR versus placebo control group using intent-to-treat analysis. Secondary outcomes will include changes in pain, health related quality of life depression-related disability and community participation. A successful clinical trial could lead to more aggressive identification and treatment of MDD as well as improved health and quality of life in this important population.
Detailed Description
Depression is likely the most prevalent and disabling psychological complication associated with spinal cord injury (SCI). The prevalence of major depression in people with SCI is 22% or two to six times higher than in the general population. Depression is linked to a myriad of adverse outcomes including poor subjective health, poor community integration, higher rates of medical complications and high rates of suicide. Surprisingly there are no randomized controlled trials for treating major depressive disorder (MMD) in people with SCI. Despite the widespread use of antidepressants in this population, the common assumption that antidepressant medications are effective and well-tolerated among people with SCI is uncertain. Multiple factors such as severe stresses, bereavement and loss of rewarding activities may complicate treatment. Treatment trials suggest antidepressants may not be as effective in people with medical/neurological conditions as they are with depression that develops as a primary condition. For almost 20 years clinicians and scientists have called for controlled clinical trials of antidepressants among people with SCI in order to establish evidence-based treatment. The proposed study is a multi-site, randomized, double-blind, placebo controlled trial of venlafaxine XR (Effexor XR) in 133 adults with SCI and MDD or dysthymia who are at least one month post injury. Participants aged 18-64 will be recruited from four SCI Model System sites, the University of Washington, Rehabilitation Institute of Chicago, University of Michigan, University of Alabama, Birmingham and Baylor Institute for Rehabilitation, Dallas TX. The purpose of the study is to examine the efficacy and tolerability of venlafaxine XR as a treatment for MDD. The primary outcome will be the percent of responders (those who report at least a 50% reduction in depression severity from baseline to the end of treatment) in the venlafaxine XR versus placebo control group using intent-to-treat analysis. Secondary outcomes will include changes in pain, health related quality of life and participation. A successful clinical trial could lead to more aggressive identification and treatment of MDD as well as improved health and quality of life in this important population.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Major Depressive Disorder, Dysthymia, Spinal Cord Injuries
Keywords
spinal cord injuries, major depressive disorder, dysthymia, antidepressant agents, pain, quality of life, muscle spasticity, community participation, anxiety

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
133 (Actual)

8. Arms, Groups, and Interventions

Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
identically encapsulated placebo pills 37.5 - 300 mg/day for 12 weeks
Arm Title
venlafaxine XR
Arm Type
Experimental
Arm Description
venlafaxine XR 37.5 - 300 mg/day for 12 weeks
Intervention Type
Drug
Intervention Name(s)
venlafaxine XR
Other Intervention Name(s)
Effexor XR
Intervention Description
Once daily oral dose of venlafaxine XR ranging from 37.5 mg up to 300 mg
Intervention Type
Drug
Intervention Name(s)
placebo
Other Intervention Name(s)
identically encapsulated inactive substance
Intervention Description
Once daily oral dose of placebo ranging from 37.5 mg up to 300 mg
Primary Outcome Measure Information:
Title
Hamilton Depression Rating Scale-17
Description
The 17-item Hamilton Depression Rating Scale is a clinician rated measure of depression severity (we used a structured interview version (Williams 1988) to improve inter-rater reliability). Scores range from 0-52. Higher scores indicate more severe depression. Scores of 7 or less indicate remission from depression.
Time Frame
0 weeks, 12 weeks
Title
Hamilton Depression Rating Scale-Maier Subscale
Description
The Maier is a 6-item sub scale of the Hamilton derived from Rasch analysis. It is a unidimensional scale with superior sensitivity to change. It excludes somatic items and is therefore especially appropriate for individuals who have substantial physical impairment and medical comorbidity. Scores can range from 0-22 with higher scores indicating more severe depression. Scores of 4 or less indicated in remission from depression.
Time Frame
0 weeks, 12 weeks
Secondary Outcome Measure Information:
Title
Symptom Checklist-20 Depression Subscale
Time Frame
Weeks 0, 1, 3, 6, 8, 10, 12, 24
Title
Modified Brief Pain Inventory
Time Frame
Weeks 0, 1, 3, 6, 8, 10, 12
Title
Modified Ashworth Spasticity Scale
Time Frame
Weeks 0, 1, 3, 6, 8, 10, 12
Title
Structured Clinical Interview for DSM IV Depression Module
Time Frame
Weeks 0, 12, 24
Title
SF-12
Time Frame
Weeks 0, 12, 24
Title
Side Effects Checklist
Time Frame
Weeks 0, 1, 3, 6, 8, 10, 12
Title
Craig Handicap and Reporting Technique
Time Frame
Weeks 0, 12
Title
Satisfaction With Life
Time Frame
Weeks 0, 12
Title
Sheehan Disability Scale
Time Frame
Weeks 0, 12
Title
Clinical Global Impression
Time Frame
Weeks 0, 1, 3, 6, 8, 10, 12
Title
Patient Global Impression
Time Frame
Weeks 0, 1, 3, 6, 8, 10, 12
Title
Hamilton Rating Scale for Anxiety
Time Frame
Weeks 0, 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Spinal cord injury (ASIA A-D) At least one month post injury Meets DSM IV criteria for major depression or dysthymia on the SCID At least moderately severe depression (PHQ-9 score >= 10) Within reasonable travel distance to one of the study sites Exclusion Criteria: Current DSM IV alcohol or drug dependence History of bipolar disorder or psychosis History of >= 2 suicide attempts or suicide attempt with 5 years Current suicidal intent or plan Medical contraindications Non-English speaker Clinically significant cognitive/language impairment History of allergic reaction to venlafaxine XR or use of MAO-I with 2 weeks Current use of antidepressant medications (will not exclude if on low dose of a tricyclic antidepressant or trazodone for pain, sleep, or bladder), psychotherapy for depression, or electroconvulsive therapy Pregnant or lactating women or women of childbearing potential who are not willing to use a reliable form of contraception Unstable medical condition, as determined by physical examination, CBC w/ platelets (including hematocrit, hemoglobin, WBC, differential), serum chemistry panel (serum sodium, potassium, chloride, bicarbonate, BUN, creatinine, glucose), liver transaminases (AST, ALT), thyroid stimulating hormone (TSH), urinalysis, supine diastolic blood pressure (SDBP) > 90 mm Hg, or near terminal illness (primary care physician estimates that patient has < 1 year to live) Anticipated major surgical procedures within the 12 weeks of randomization Use of an investigational drug within 30 days Use of psychoactive medications, including corticosteroids and anticonvulsants, that have not been at a stable dose for at least 2 weeks Use of anxiolytic, sedative-hypnotic, or other psychotropic drug or substance (including St. John's Wort) within 7 days of start of double-blind treatment. If the patient is taking a sedative deemed necessary for sleep induction or spasticity, the dosage must have been stable for at least 2 weeks. Use of anticholinergic, low-dose tricyclic antidepressant, GABAergic or adrenergic medications for spasticity are permitted if at a stable dose for at least 2 weeks. Refusal to participate
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Charles H. Bombardier, PhD
Organizational Affiliation
University of Washington School of Medicine, Department of Rehabilitation Medicine
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jesse R. Fann, MD, MPH
Organizational Affiliation
University of Washington School of Medicine, Department of Psychiatry and Behavioral Science
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294-0111
Country
United States
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33124
Country
United States
Facility Name
Rehabilitation Institute of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611-2654
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109-0491
Country
United States
Facility Name
Baylor Institute for Rehabilitation
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
University of Washington/Harborview Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
25613597
Citation
McCullumsmith CB, Kalpakjian CZ, Richards JS, Forchheimer M, Heinemann AW, Richardson EJ, Wilson CS, Barber J, Temkin N, Bombardier CH, Fann JR; PRISMS Investigators. Novel risk factors associated with current suicidal ideation and lifetime suicide attempts in individuals with spinal cord injury. Arch Phys Med Rehabil. 2015 May;96(5):799-808. doi: 10.1016/j.apmr.2014.12.017. Epub 2015 Jan 19.
Results Reference
derived
PubMed Identifier
25607727
Citation
Fann JR, Bombardier CH, Richards JS, Wilson CS, Heinemann AW, Warren AM, Brooks L, McCullumsmith CB, Temkin NR, Warms C, Tate DG; PRISMS Investigators. Venlafaxine extended-release for depression following spinal cord injury: a randomized clinical trial. JAMA Psychiatry. 2015 Mar;72(3):247-58. doi: 10.1001/jamapsychiatry.2014.2482.
Results Reference
derived
PubMed Identifier
22440484
Citation
Bombardier CH, Fann JR, Tate DG, Richards JS, Wilson CS, Warren AM, Temkin NR, Heinemann AW; PRISMS Investigators. An exploration of modifiable risk factors for depression after spinal cord injury: which factors should we target? Arch Phys Med Rehabil. 2012 May;93(5):775-81. doi: 10.1016/j.apmr.2011.12.020. Epub 2012 Mar 20.
Results Reference
derived
PubMed Identifier
21255766
Citation
Fann JR, Bombardier CH, Richards JS, Tate DG, Wilson CS, Temkin N; PRISMS Investigators. Depression after spinal cord injury: comorbidities, mental health service use, and adequacy of treatment. Arch Phys Med Rehabil. 2011 Mar;92(3):352-60. doi: 10.1016/j.apmr.2010.05.016. Epub 2011 Jan 20.
Results Reference
derived

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Project to Improve Symptoms and Mood in People With Spinal Cord Injury

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