Atomoxetine and Executive Function in PTSD
NCT Number: NCT06573970
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE4
Conditions: Posttraumatic Stress Disorder With Attention Defic
Interventions: DRUG: Atomoxetine
Sponsor: VA Office of Research and Development
Collaborators: Medical University of South Carolina
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 160
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: QUADRUPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2024-12-16
Completion Date: 2028-10-31
Locations: Ralph H. Johnson VA Medical Center, Charleston, SC, Charleston, South Carolina, 29401-5703, United States

Summary:
Attention deficits (AD) frequently co-occur with posttraumatic stress disorder (PTSD). The presence of AD is associated with greater PTSD clinical severity and poorer clinical outcomes. Knowledge regarding the mechanism underlying this association is limited, though the emerging evidence has indicated that executive function deficit (EFD) is strongly correlated with AD and PTSD symptoms. While treatments developed for PTSD have existed for years, a substantial portion of individuals do not fully respond to conventional treatment. Accumulating evidence suggest that attention deficit (AD) and EFD may be a driving force for PTSD treatment resistance. However, treatment of executive impairment in PTSD is very limited. As a result, untreated co-occurring AD and EFD in PTSD poses severe negative impacts on patients' functional recovery, treatment outcomes, and quality of life (QoL). Given that up to 50% of patients do not respond well to the first-line pharmacological PTSD treatments, it is imperative to seek novel treatment strategies to improve EF that may improve both standard treatment response and QoL, social function. The proposed study directly addresses this knowledge gap by testing the efficacy of atomoxetine (ATX) in improving EF and attention among Veterans with PTSD, which will further improve Veterans' QoL and social function. ATX represents a promising novel candidate pharmacotherapy for individuals with PTSD. ATX is a non-stimulant selective norepinephrine reuptake inhibitor (SNRI), approved by the FDA for the treatment of ADHD. Studies suggest that ATX, unlike stimulants, lacks addictive properties and shows efficacy in the treatment of comorbid depression and anxiety, which is ideal in the treatment of PTSD. Data from the investigators' preliminary study provides encouraging support for the therapeutic potential of ATX in improving EF in Veterans with comorbid PTSD/ADHD. The investigators' recent research uncovered a higher rate of ADHD among Veterans with PTSD, and the comorbid AD symptoms were correlated with PTSD severity and poorer treatment outcomes. Treatment with ATX showed significant symptoms reduction in ADHD and improvement in inhibitory function in Veterans with ADHD/PTSD. In the proposed study, the investigators will focus on ATX in improvement of EF and attention, and further psycho-social life function and QoL. The investigators will (1) employ a randomized, double-blind design that will consist of 12 weeks of treatment with ATX or placebo medication; (2) use standardized, repeated dependent measures to rigorously assess AD and EFD symptomatology; (3) measure impairment in associated mental and behavioral health problems (e.g., attention deficit, depression, anxiety, suicidality, QoL, family/social functioning); and (4) use response inhibition task GoNogo, working memory and attention tests Digit Span and Trail Making to investigate the underlying pathophysiology of PTSD and prognostic indicators of treatment outcome. To achieve these goals, the investigators have assembled a multidisciplinary team with expertise in PTSD, ADHD clinical trials, and human laboratory paradigms who have successfully collaborated in the past and are uniquely qualified to implement this type of investigation. The proposed project is directly responsive to the mission of the VA-RRD "to maximize Veterans' functional independence, quality of life and participation in their lives and community." Successful completion of this study will provide a platform for a large multi-center trial to further confirm the important role of EF in PTSD treatment outcomes. The findings from this study will provide critically needed evidence to help inform clinical practice guidelines on the treatment of PTSD. The outcome of the proposed research will be significant, because it provides a knowledge base to allow for development of new PTSD intervention strategies. More importantly, this clinical trial may immediately benefit Veterans by enhancing their cognitive function, reducing AD related disability, and further improving quality of life for Veterans who suffer from PTSD.

Primary Outcome Measures: Behavior Rating Inventory of Executive Function-Adult (BRIEF-A), The BRIEF-A is a 75-item questionnaire that assesses adult executive functioning and self-regulation. It's suitable for adults ages 18-90 with a wide range of developmental, neurological, psychiatric, and systemic disorders, 15 to 20 minutes
Secondary Outcome Measures: Conners' Adult ADHD Rating Scales-Self Report: Short Version (CAARS-S:S), The CAARS-S:S is a 26-item questionnaire that assesses symptoms of ADHD in persons aged 18 years. T-scores above 65 indicate a likelihood of moderate to severe ADHD symptoms and impairment., 10 to 15 minutes|Clinician Administered PTSD Scale 5 (CAPS), The CAPS-5 is a 30-item structured interview that assesses both target PTSD symptoms and impact of symptoms on social and occupational functioning. The CAPS-5 is the gold standard for diagnosing PTSD. It provides both a dichotomous index for PTSD diagnoses and PTSD symptom severity., 20 minutes
Other Outcome Measures: The Adult ADHD Quality of Life-29 (AAQOL-29), AAQoL-29 is a participant-reported outcome measure used to examine disease specific functional impairments and quality of life for adults with ADHD. The AAQOL-29 includes Life Productivity, Psychological Health, Quality of Relationships, and Life Outlook subscales. Higher scores on the AAQOL-29 indicate better functioning., 15 minutes