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

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.

Condition or disease	Intervention/treatment	Phase
Major Depressive Disorder; Dysthymia; Spinal Cord Injuries	Drug: venlafaxine XR; Drug: placebo	Phase 4

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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	133 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	A Controlled Trial of Venlafaxine XR for Major Depression After Spinal Cord Injury: A Multi-site Study
Study Start Date :	July 2007
Actual Primary Completion Date :	September 2012
Actual Study Completion Date :	September 2012

Arms and Interventions

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Arm	Intervention/treatment
Placebo Comparator: placebo; identically encapsulated placebo pills 37.5 - 300 mg/day for 12 weeks	Drug: placebo; Once daily oral dose of placebo ranging from 37.5 mg up to 300 mg; Other Name: identically encapsulated inactive substance
Experimental: venlafaxine XR; venlafaxine XR 37.5 - 300 mg/day for 12 weeks	Drug: venlafaxine XR; Once daily oral dose of venlafaxine XR ranging from 37.5 mg up to 300 mg; Other Name: Effexor XR

Outcome Measures

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Primary Outcome Measures :

1. Hamilton Depression Rating Scale-17 [ Time Frame: 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.
2. Hamilton Depression Rating Scale-Maier Subscale [ Time Frame: 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 :

1. Symptom Checklist-20 Depression Subscale [ Time Frame: Weeks 0, 1, 3, 6, 8, 10, 12, 24 ]
2. Modified Brief Pain Inventory [ Time Frame: Weeks 0, 1, 3, 6, 8, 10, 12 ]
3. Modified Ashworth Spasticity Scale [ Time Frame: Weeks 0, 1, 3, 6, 8, 10, 12 ]
4. Structured Clinical Interview for DSM IV Depression Module [ Time Frame: Weeks 0, 12, 24 ]
5. SF-12 [ Time Frame: Weeks 0, 12, 24 ]
6. Side Effects Checklist [ Time Frame: Weeks 0, 1, 3, 6, 8, 10, 12 ]
7. Craig Handicap and Reporting Technique [ Time Frame: Weeks 0, 12 ]
8. Satisfaction With Life [ Time Frame: Weeks 0, 12 ]
9. Sheehan Disability Scale [ Time Frame: Weeks 0, 12 ]
10. Clinical Global Impression [ Time Frame: Weeks 0, 1, 3, 6, 8, 10, 12 ]
11. Patient Global Impression [ Time Frame: Weeks 0, 1, 3, 6, 8, 10, 12 ]
12. Hamilton Rating Scale for Anxiety [ Time Frame: Weeks 0, 12 ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 64 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, Alabama
University of Alabama
Birmingham, Alabama, United States, 35294-0111
United States, Florida
University of Miami
Miami, Florida, United States, 33124
United States, Illinois
Rehabilitation Institute of Chicago
Chicago, Illinois, United States, 60611-2654
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109-0491
United States, Texas
Baylor Institute for Rehabilitation
Dallas, Texas, United States, 75246
United States, Washington
University of Washington/Harborview Medical Center
Seattle, Washington, United States, 98104

Sponsors and Collaborators

University of Washington

University of Michigan

Shirley Ryan AbilityLab

University of Alabama at Birmingham

Baylor Health Care System

University of Miami

New York University

Investigators

Principal Investigator:	Charles H. Bombardier, PhD	University of Washington School of Medicine, Department of Rehabilitation Medicine
Principal Investigator:	Jesse R. Fann, MD, MPH	University of Washington School of Medicine, Department of Psychiatry and Behavioral Science

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

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.

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.

Responsible Party:	Charles Bombardier, Primary Investigator, University of Washington
ClinicalTrials.gov Identifier:	NCT00592384 History of Changes
Other Study ID Numbers:	31665-D; H133A060107; ( Other Grant/Funding Number: National Institute on Disability and Rehabilitation Research )
First Posted:	January 14, 2008
Results First Posted:	January 1, 2015
Last Update Posted:	January 1, 2015
Last Verified:	December 2014

Keywords provided by Charles Bombardier, University of Washington:

spinal cord injuries; major depressive disorder; dysthymia; antidepressant agents; pain	quality of life; muscle spasticity; community participation; anxiety

Additional relevant MeSH terms:

Spinal Cord Injuries; Wounds and Injuries; Depressive Disorder; Depression; Depressive Disorder, Major; Dysthymic Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases	Trauma, Nervous System; Venlafaxine Hydrochloride; Serotonin and Noradrenaline Reuptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Physiological Effects of Drugs; Antidepressive Agents, Second-Generation; Antidepressive Agents; Psychotropic Drugs