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

Major Depressive Disorder Clinical Trial

— PRISMS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00592384
• Other study ID #: 31665-D
• Secondary ID: H133A060107
• Status: Completed
• Phase: Phase 4
• First received: January 1, 2008
• Last updated: December 31, 2014
• Start date: July 2007
• Est. completion date: September 2012

Study information

• Verified date: December 2014
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 133
• Est. completion date: September 2012
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 64 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Dysthymia
• Major Depressive Disorder
• Spinal Cord Injuries

Intervention

Drug:
• venlafaxine XR
Once daily oral dose of venlafaxine XR ranging from 37.5 mg up to 300 mg
• placebo
Once daily oral dose of placebo ranging from 37.5 mg up to 300 mg

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Alabama	Birmingham	Alabama
United States	Rehabilitation Institute of Chicago	Chicago	Illinois
United States	Baylor Institute for Rehabilitation	Dallas	Texas
United States	University of Miami	Miami	Florida
United States	University of Washington/Harborview Medical Center	Seattle	Washington

Sponsors (7)

Lead Sponsor	Collaborator
University of Washington	Baylor Health Care System, New York University, Rehabilitation Institute of Chicago, University of Alabama at Birmingham, University of Miami, University of Michigan

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Secondary	Symptom Checklist-20 Depression Subscale		Weeks 0, 1, 3, 6, 8, 10, 12, 24	No
Secondary	Modified Brief Pain Inventory		Weeks 0, 1, 3, 6, 8, 10, 12	No
Secondary	Modified Ashworth Spasticity Scale		Weeks 0, 1, 3, 6, 8, 10, 12	Yes
Secondary	Structured Clinical Interview for DSM IV Depression Module		Weeks 0, 12, 24	No
Secondary	SF-12		Weeks 0, 12, 24	No
Secondary	Side Effects Checklist		Weeks 0, 1, 3, 6, 8, 10, 12	Yes
Secondary	Craig Handicap and Reporting Technique		Weeks 0, 12	No
Secondary	Satisfaction With Life		Weeks 0, 12	No
Secondary	Sheehan Disability Scale		Weeks 0, 12	No
Secondary	Clinical Global Impression		Weeks 0, 1, 3, 6, 8, 10, 12	Yes
Secondary	Patient Global Impression		Weeks 0, 1, 3, 6, 8, 10, 12	Yes
Secondary	Hamilton Rating Scale for Anxiety		Weeks 0, 12	No