Feasibility Study of Duloxetine in the Treatment of Depression in Patients With Traumatic Brain Injury (Duloxetine)

Prevention of Depression and Enhancement of Cognitive Recovery Following Traumatic Brain Injury With Duloxetine

The primary objective of the study is to compare the efficacy of duloxetine 60 mg by mouth daily with placebo in the prevention of depression associated with mild/moderate traumatic brain injury and to enhance cognitive function.

Study Overview

• Status: Terminated
• Conditions: Depression; Traumatic Brain Injury
• Intervention / Treatment: Drug: Duloxetine; Drug: Sugar pill

Detailed Description

The primary objective of the study is to compare the efficacy of duloxetine 60 mg by mouth daily with placebo in the prevention of depression associated with mild/moderate traumatic brain injury and to enhance cognitive function. Research exploring the use of selective serotonin reuptake inhibitors in the treatment of post-traumatic depression generally validates this approach (Horsfield et al., 2002). However, the literature suggests that serotonin/norepinephrine reuptake inhibitors such as duloxetine may be more effective in the treatment of depression.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46254
      • Rehabilitation Hospital of Indiana

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Study participants will be 40 men and women between the ages of 18 and 75 who provide appropriate consent and who are agreeable to study requirements
• Diagnosed with mild to moderate traumatic brain injury as defined by an initial Mayo Traumatic Brain Injury Severity Scale
• Have memory impairments defined by a Hopkins Verbal Learning Test delayed recall score which falls less than or equal to 1.5 standard deviation below the mean.

Exclusion Criteria:

• Refusal to give informed consent
• A previous Central Nervous System illness or injury, including seizure that exhibits residual symptoms.
• Current post-traumatic seizure disorder
• A previous diagnosis of a psychotic disorder
• Current or previous (in the last 6 months) treatment history for alcohol or substance dependency
• Medications affecting noradrenergic or dopaminergic systems, alpha-adrenergic antihypertensives, antidepressant, phenobarbital, Monoamine oxidase inhibitor (MAOI), scheduled benzodiazepines, psychoactive herbal supplements (including Kava, St. John's wort), or nutritional supplements or within at least 14 days of discontinuing treatment with the above medications or supplements.
• A known suicide risk
• A pregnant or breastfeeding woman
• Uncontrolled narrow-angle glaucoma
• Serious and/or unstable medical comorbidity (e.g., AIDS, cancer, history of uncontrolled hypertension or cardiovascular disease) psychological condition, or clinically significant laboratory abnormality that in the opinion of the investigator would compromise participation in the study or be likely to lead to hospitalization during the course of the study
• Liver enzymes > 1.5 times upper limit of normal
• Patients with end-stage renal disease (requiring dialysis) or severe renal impairment
• Known hypersensitivity to duloxetine or any of the inactive ingredients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Duloxetine; Duloxetine 30 mg. PO daily to 120mg. PO daily for nine months in patients who have suffered a traumatic brain injury at least six months previously.	Drug: Duloxetine; Duloxetine 30 mg. PO daily to 120mg. PO daily for nine months in patients who have suffered a traumatic brain injury at least six months previously.; Other Names: Cymbalta
Placebo Comparator: Sugar pill; Sugar pills 30 mg. PO daily to 120mg. PO daily for nine months in patients who have suffered a traumatic brain injury at least six months previously.	Drug: Sugar pill; Sugar pills 30 mg. PO daily to 120mg. PO daily for nine months in patients who have suffered a traumatic brain injury at least six months previously.; Other Names: Lactose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hamilton Rating Scale for Depression	To compare the efficacy of duloxetine 30 mg. PO daily to 120mg. PO daily with placebo in the prevention of depression associated with mild/moderate traumatic brain injury, utilizing the Hamilton Rating Scale for Depression (Hamilton, 1960; HAM-D) as the primary efficacy measure.	9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hopkins Verbal Learning Test	To compare the effect of duloxetine vs. placebo on the recovery of memory functions of patients with traumatic brain injury, utilizing the 20-minute delayed recall score of the Hopkins Verbal Learning Test (Brandt, 1991) as the secondary efficacy measure.	9 months

Collaborators and Investigators

• Sponsor: Rehabilitation Hospital of Indiana
• Collaborators: Eli Lilly and Company
• Investigators: Principal Investigator: Lance Trexler, Ph.D., Rehabilitation Hospital of Indiana

Study record dates

Study Major Dates

• Study Start: September 1, 1996
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: October 15, 2010
• First Submitted That Met QC Criteria: October 15, 2010
• First Posted (Estimate): October 18, 2010

Study Record Updates

• Last Update Posted (Estimate): December 17, 2014
• Last Update Submitted That Met QC Criteria: December 15, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: Depression; Traumatic brain injury; Duloxetine; Cymbalta; impaired cognitive function
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mood Disorders; Craniocerebral Trauma; Trauma, Nervous System; Depression; Depressive Disorder; Brain Injuries; Wounds and Injuries; Brain Injuries, Traumatic; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Dopamine Agents; Serotonin and Noradrenaline Reuptake Inhibitors; Duloxetine Hydrochloride
• Other Study ID Numbers: RHI 05-096; F1J-US-X025 (Other Identifier: Eli Lilly and Co.)