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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Major Depressive Disorder, Dysthymia, Spinal Cord Injuries

Intervention / Treatment
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* Drug: venlafaxine XR
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: placebo<br>identically encapsulated placebo pills 37.5 - 300 mg/day for 12 weeks | Drug: placebo<br>* Once daily oral dose of placebo ranging from 37.5 mg up to 300 mg<br>* Other names: identically encapsulated inactive substance;|
| Experimental: venlafaxine XR<br>venlafaxine XR 37.5 - 300 mg/day for 12 weeks | Drug: venlafaxine XR<br>* Once daily oral dose of venlafaxine XR ranging from 37.5 mg up to 300 mg<br>* Other names: Effexor XR;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 0 weeks, 12 weeks | 
| 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. | 0 weeks, 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptom Checklist-20 Depression Subscale |  | Weeks 0, 1, 3, 6, 8, 10, 12, 24 | 
| Modified Brief Pain Inventory |  | Weeks 0, 1, 3, 6, 8, 10, 12 | 
| Modified Ashworth Spasticity Scale |  | Weeks 0, 1, 3, 6, 8, 10, 12 | 
| Structured Clinical Interview for DSM IV Depression Module |  | Weeks 0, 12, 24 | 
| SF-12 |  | Weeks 0, 12, 24 | 
| Side Effects Checklist |  | Weeks 0, 1, 3, 6, 8, 10, 12 | 
| Craig Handicap and Reporting Technique |  | Weeks 0, 12 | 
| Satisfaction With Life |  | Weeks 0, 12 | 
| Sheehan Disability Scale |  | Weeks 0, 12 | 
| Clinical Global Impression |  | Weeks 0, 1, 3, 6, 8, 10, 12 | 
| Patient Global Impression |  | Weeks 0, 1, 3, 6, 8, 10, 12 | 
| Hamilton Rating Scale for Anxiety |  | Weeks 0, 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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spinal cord injuries, major depressive disorder, dysthymia, antidepressant agents, pain, quality of life, muscle spasticity, community participation, anxiety