Atomoxetine in Veterans With Comorbid ADHD/PTSD

NCT ID: NCT02287038

Last Updated: 2019-04-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-10-15
• Study Completion Date: 2017-04-14

Brief Summary

The current available treatments for PTSD are not fully effective for cognitive symptoms of PTSD and have high drop-out and poor engagement, two factors found to be most indicative of overall return to functioning for patients with PTSD. The proposed study directly addresses this knowledge gap by conducting a pilot, fixed-dose, randomized, double-blind, placebo-controlled, and cross-over trial using atomoxetine (ATX) as an add-on medication to other therapies to testing the efficacy of ATX in reducing ADHD cognitive symptoms among veterans with comorbid ADHD/PTSD. Successful completion of this pilot clinical trial may build a platform for future large scale double-blind, placebo-controlled studies using either atomoxetine or other cognitive enhancing medications.

Detailed Description

Combat Veterans with posttraumatic stress disorder (PTSD) often show cognitive impairments in attention, working memory, executive functions, and inhibitory control, a cluster of symptoms resembling symptoms of ADHD. The presence of comorbid ADHD cognitive symptoms is often associated with greater PTSD clinical severity and poorer treatment outcomes. While treatments for the avoidance, arousal, and re-experiencing symptoms associated with PTSD for military personnel are readily available, substantial gaps exist in the treatment of the cognitive deficits associated with PTSD. As a result, untreated co-occurring ADHD cognitive symptoms in PTSD may have severe negative impacts on patients' functional recovery, treatment outcome, and quality of life. The proposed study directly addresses this knowledge gap by testing the feasibility and preliminary efficacy of atomoxetine (ATX) in treatment of ADHD cognitive symptoms among those with comorbid ADHD/PTSD. This is a small prospective, 10-week, fixed-dose, randomized, double-blind, placebo-controlled, and cross-over trial of ATX as an add-on medication to other therapies in Veterans with comorbid ADHD/PTSD. Primary outcome measures will be ADHD cognitive symptom reduction and quality of life improvement as measured by the Adult ADHD Rating Scales-Self-Report: Short Version (CAARS-S:S) and the Adult ADHD Quality of Life-29 (AAQoL-29). Secondary outcome measures will be PTSD and depressive symptoms reduction as measured by the Clinician Administered PTSD Scale (CAPS), the Hamilton Depression Scale (HAM-D). In addition to subjective measures, the response inhibition task Go/NoGo (GNG) will be used as objective assessments to measure ATX treatment outcomes. The proposed work is innovative; it applies novel therapeutic agent to treat cognitive symptoms in PTSD. To our knowledge, this is the first study to apply a SNRI to address an often overlooked PTSD-cognitive deficit. This study is directly responsive to the mission of RR&D-SPiRE "to maximize functional recovery" of cognitive function in PTSD. The outcome of the proposed research will be significant, because it provides a knowledge base to help determine who is at risk for developing treatment resistance among PTSD patients, thereby allowing for development of early intervention strategies. More importantly, this clinical trial may immediate benefit Veterans by enhancing their cognitive function, reducing ADHD symptoms related disability, and further improving quality of life for veterans suffer from comorbid ADHD/PTSD.

Conditions

Post Traumatic Stress Disorder; Attention Deficit Hyperactivity Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Atomoxetine 80mg

Atomoxetine (fixed dose of 80mg), a non-stimulant medication, FDA approve for treatment of ADHD. The active drug will be applied in first phase in group one and in second phase in group two

Group Type: ACTIVE_COMPARATOR

Atomoxetine 80 MG

Intervention Type: DRUG

Subjects will be randomized and assigned by the study investigator into crossover group 1 (Atomoxetine 80mg at Phase I, then placebo at Phase II) or group 2 (placebo at Phase I, then Atomoxetine at Phase II) with both placebo and medication administered through pharmacy. There was a 1-week interval between the two phases.

Placebo

A pharmaceutically inert substance, which will be given to group one in their second phase and group tow in first phase.

Group Type: PLACEBO_COMPARATOR

Atomoxetine 80 MG

Intervention Type: DRUG

Subjects will be randomized and assigned by the study investigator into crossover group 1 (Atomoxetine 80mg at Phase I, then placebo at Phase II) or group 2 (placebo at Phase I, then Atomoxetine at Phase II) with both placebo and medication administered through pharmacy. There was a 1-week interval between the two phases.

Interventions

Atomoxetine 80 MG

Subjects will be randomized and assigned by the study investigator into crossover group 1 (Atomoxetine 80mg at Phase I, then placebo at Phase II) or group 2 (placebo at Phase I, then Atomoxetine at Phase II) with both placebo and medication administered through pharmacy. There was a 1-week interval between the two phases.

Intervention Type: DRUG

Other Intervention Names

Strattera

Eligibility Criteria

Inclusion Criteria

• Veterans age 20 to 60 with PTSD and significant ADHD symptoms (CAARS-S:S > 65);
• Good physical health.
• Evidence of combat as defined by:

• Trauma exposure sufficient to meet Category A of PTSD criteria (Breslau and Kessler 2001)

Exclusion Criteria

• Age younger than 20 or greater than 60.
• Known sensitivity to ATX
• Presence of disorders that could conceivable be exacerbated by atomoxetine (specifically, narrow angle closure glaucoma, urinary outflow obstruction, hypertension, and neurological disorders, particularly tics and Tourette's syndrome, or a history of epilepsy or seizures).
• Use of concomitant medication that could potentially interact with atomoxetine including monoamine oxidase inhibitors (MAOI), antihypertensive medication, or any concomitant medication that was a cytochrome 2D6 inhibitor (CYP2D6), since atomoxetine's elimination involves the CYP2D6 system.
• An active or lifetime major mental health diagnosis as determined by DSM-IV Axis I Disorders, including schizophrenia, schizoaffective disorder, psychotic disorder not otherwise specified, bipolar I disorder, bipolar II disorder, bipolar disorder not otherwise specified. The project will allow presence of depressive disorders if the depressive episodes are secondary to PTSD.
• Current substance dependence and abuse (within 3 month).
• Females who are pregnant.
• Suicidal thoughts and behavior. b. Sources of Material

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

VA Office of Research and Development

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Zhewu Wang, MD

Role: PRINCIPAL_INVESTIGATOR

Ralph H. Johnson VA Medical Center, Charleston, SC

Locations

Ralph H. Johnson VA Medical Center, Charleston, SC

Charleston, South Carolina, United States

Countries

United States

References

Wang Z, Zuschlag ZD, Myers US, Hamner M. Atomoxetine in comorbid ADHD/PTSD: A randomized, placebo controlled, pilot, and feasibility study. Depress Anxiety. 2022 Apr;39(4):286-295. doi: 10.1002/da.23248. Epub 2022 Mar 21.

Reference Type: DERIVED

PMID: 35312136 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

I01BX007080

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

D1725-P

Identifier Type: -

Identifier Source: org_study_id