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

NCT00592384 | Completed Phase 4 Results DMC

• 2 other identifiers: 31665-DH133A060107;
• Study Type: interventional
• Target: 133
• Locations: 1 country
• Sites: 6

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.

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (12)

• 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

Study Arms (2)

placebo

PLACEBO COMPARATOR

identically encapsulated placebo pills 37.5 - 300 mg/day for 12 weeks

Drug: placebo

venlafaxine XR

EXPERIMENTAL

venlafaxine XR 37.5 - 300 mg/day for 12 weeks

Drug: venlafaxine XR

Interventions

venlafaxine XR DRUG

Once daily oral dose of venlafaxine XR ranging from 37.5 mg up to 300 mg

Also known as: Effexor XR

venlafaxine XR

placebo DRUG

Once daily oral dose of placebo ranging from 37.5 mg up to 300 mg

Also known as: identically encapsulated inactive substance

placebo

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Washington: lead
• University of Michigan: collaborator
• Shirley Ryan AbilityLab: collaborator
• University of Alabama at Birmingham: collaborator
• Baylor Health Care System: collaborator
• University of Miami: collaborator
• New York University: collaborator

Study Sites (6)

University of Alabama

Birmingham, Alabama, 35294-0111, United States

Location

University of Miami

Miami, Florida, 33124, United States

Location

Rehabilitation Institute of Chicago

Chicago, Illinois, 60611-2654, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109-0491, United States

Location

Baylor Institute for Rehabilitation

Dallas, Texas, 75246, United States

Location

University of Washington/Harborview Medical Center

Seattle, Washington, 98104, United States

Location

Related Publications (4)

• 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.

  PMID: 25613597 DERIVED

• 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.

  PMID: 25607727 DERIVED

• 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.

  PMID: 22440484 DERIVED

• 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.

  PMID: 21255766 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major; Dysthymic Disorder; Spinal Cord Injuries; Pain; Muscle Spasticity; Anxiety Disorders

Interventions

Venlafaxine Hydrochloride

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations

Intervention Hierarchy (Ancestors)

Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Organic Chemicals; Phenethylamines; Ethylamines; Amines; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Lipids

Results Point of Contact

• Title: Dr. Jesse R. Fann
• Organization: University of Washington

fann@uw.edu

206 6854280

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Primary Investigator

Study Record Dates

• First Submitted: January 1, 2008
• First Posted: January 14, 2008
• Study Start: July 1, 2007
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2012
• Last Updated: January 1, 2015
• Results First Posted: January 1, 2015

Record last verified: 2014-12

Locations

US (6)