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

Phase 4

Completed

• Conditions: Spinal Cord Injuries; Major Depressive Disorder; Dysthymia
• Interventions: Drug: venlafaxine XR; Drug: placebo

• Registration Number: NCT00592384
• Lead Sponsor: University of Washington

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.

Study Timeline

• Study Start: 2007-07
• Study First Submitted: 2008-01-01
• Study First Submitted QC: 2008-01-01
• Study First Posted: 2008-01-14
• Primary Completion: 2012-09
• Study Completion: 2012-09
• Results First Submitted: 2014-06-11
• Status Verified: 2014-12
• Results First Submitted QC: 2014-12-31
• Last Update Submitted: 2014-12-31
• Results First Posted: 2015-01-01
• Last Update Posted: 2015-01-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 133

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
venlafaxine XR	venlafaxine XR	venlafaxine XR 37.5 - 300 mg/day for 12 weeks
placebo	placebo	identically encapsulated placebo pills 37.5 - 300 mg/day for 12 weeks

Primary Outcome Measures

Name	Time	Method
Hamilton Depression Rating Scale-17	0 weeks, 12 weeks	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	0 weeks, 12 weeks	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

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

Trial Locations

Locations (6)

University of Miami; 🇺🇸 Miami, Florida, United States

University of Alabama; 🇺🇸 Birmingham, Alabama, United States

Rehabilitation Institute of Chicago; 🇺🇸 Chicago, Illinois, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Baylor Institute for Rehabilitation; 🇺🇸 Dallas, Texas, United States

University of Washington/Harborview Medical Center; 🇺🇸 Seattle, Washington, United States