Official Title: “A Controlled Trial of Venlafaxine XR for Major Depression After Spinal Cord Injury: A Multi-Site Study”

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 168 adults with SCI and major depressive disorder (MDD) who are at least one year post injury. Participants will be recruited from four SCI Model System sites, the University of Washington, Rehabilitation Institute of Chicago, University of Michigan and University of Alabama, Birmingham. 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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: June 2011

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 168 adults with SCI and MDD who are at least one year 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 and University of Alabama, Birmingham. 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.

Intervention(s) in this Clinical Trial

• Drug: venlafaxine XR
  • Once daily oral dose ranging from 37.5 mg up to 300 mg
• Drug: placebo
  • identically encapsulated inactive substance

Arms, Groups and Cohorts in this Clinical Trial

• Placebo Comparator: 1
• Experimental: 2

Primary Measures

• Hamilton Depression Rating Scale
  • Time Frame: weeks 0, 1, 3, 6, 8, 10, 12, 24
    Safety Issue?: No

Secondary Measures

• Symptom Checklist-20 Depression subscale
  • Time Frame: Weeks 0, 1, 3, 6, 8, 10, 12, 24
    Safety Issue?: No
• Modified Brief Pain Inventory
  • Time Frame: Weeks 0, 1, 3, 6, 8, 10, 12
    Safety Issue?: No
• Modified Ashworth Spasticity Scale
  • Time Frame: Weeks 0, 1, 3, 6, 8, 10, 12
    Safety Issue?: Yes
• Structured Clinical Interview for DSM IV Depression Module
  • Time Frame: Weeks 0, 12, 24
    Safety Issue?: No
• SF-12
  • Time Frame: Weeks 0, 12, 24
    Safety Issue?: No
• Side Effects Checklist
  • Time Frame: Weeks 0, 1, 3, 6, 8, 10, 12
    Safety Issue?: Yes
• Craig Handicap and Reporting Technique
  • Time Frame: Weeks 0, 12
    Safety Issue?: No
• Satisfaction with Life
  • Time Frame: Weeks 0, 12
    Safety Issue?: No
• Sheehan Disability Scale
  • Time Frame: Weeks 0, 12
    Safety Issue?: No
• Clinical Global Impression
  • Time Frame: Weeks 0, 1, 3, 6, 8, 10, 12
    Safety Issue?: Yes
• Patient Global Impression
  • Time Frame: Weeks 0, 1, 3, 6, 8, 10, 12
    Safety Issue?: Yes
• Hamilton Rating Scale for Anxiety
  • Time Frame: Weeks 0, 12
    Safety Issue?: No

Inclusion Criteria:

• Spinal cord injury (ASIA A-D)
• At least one year post injury
• Meets DSM IV criteria for major depression 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 64 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Washington

Overall Clinical Trial Officials and Contacts

Charles H. Bombardier, PhD Principal Investigator University of Washington School of Medicine, Department of Rehabilitation Medicine  

Overall Contact: Charles H Bombardier, PhD 206-744-3665 chb@u.washington.edu

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00592384

Study ID Number: 07-5325-D 01

ClinicalTrials.gov Identifier: NCT00592384

Health Authority: United States: Institutional Review Board