Clinical trial NCT00592384: Project to Improve Symptoms and Mood in People With Spinal Cord Injury
Official title: A Controlled Trial of Venlafaxine XR for Major Depression After Spinal Cord Injury: A Multi-site Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: 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
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: University of Michigan
name: Shirley Ryan AbilityLab
name: University of Alabama at Birmingham
name: Baylor Health Care System
name: University of Miami
name: New York University
First posted: 2008-01-14
Enrollment: 133
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Hamilton Depression Rating Scale-17
timeFrame: 0 weeks, 12 weeks
measure: Hamilton Depression Rating Scale-Maier Subscale
timeFrame: 0 weeks, 12 weeks
Secondary outcomes:
measure: Symptom Checklist-20 Depression Subscale
timeFrame: Weeks 0, 1, 3, 6, 8, 10, 12, 24
measure: Modified Brief Pain Inventory
timeFrame: Weeks 0, 1, 3, 6, 8, 10, 12
measure: Modified Ashworth Spasticity Scale
timeFrame: Weeks 0, 1, 3, 6, 8, 10, 12
measure: Structured Clinical Interview for DSM IV Depression Module
timeFrame: Weeks 0, 12, 24
measure: SF-12
timeFrame: Weeks 0, 12, 24
measure: Side Effects Checklist
timeFrame: Weeks 0, 1, 3, 6, 8, 10, 12
measure: Craig Handicap and Reporting Technique
timeFrame: Weeks 0, 12
measure: Satisfaction With Life
timeFrame: Weeks 0, 12
measure: Sheehan Disability Scale
timeFrame: Weeks 0, 12
measure: Clinical Global Impression
timeFrame: Weeks 0, 1, 3, 6, 8, 10, 12
measure: Patient Global Impression
timeFrame: Weeks 0, 1, 3, 6, 8, 10, 12
measure: Hamilton Rating Scale for Anxiety
timeFrame: Weeks 0, 12
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Chicago
country: United States
facility: Rehabilitation Institute of Chicago
state: Illinois
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Dallas
country: United States
facility: Baylor Institute for Rehabilitation
state: Texas
city: Seattle
country: United States
facility: University of Washington/Harborview Medical Center
state: Washington
Study officials:
affiliation: University of Washington School of Medicine, Department of Rehabilitation Medicine
name: Charles H. Bombardier, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Washington School of Medicine, Department of Psychiatry and Behavioral Science
name: Jesse R. Fann, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.