Post Traumatic Stress DisorderPhase 4NCT02287038
Atomoxetine in Veterans With Comorbid ADHD/PTSD
A Phase 4 study testing Atomoxetine 80 MG in people with Post Traumatic Stress Disorder and Attention Deficit Hyperactivity Disorder, run by VA Office of Research and Development at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 60 years
- Conditions the study is for
- Post Traumatic Stress Disorder, Attention Deficit Hyperactivity Disorder
- What is being tested?
- Atomoxetine 80 MG
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Oct 2014to 14 Apr 2017
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Ralph H. Johnson VA Medical Center, Charleston, SC
Charleston, South Carolina, 29401-5799
About this study
Official title: Atomoxetine in Comorbid ADHD/PTSD: A Pilot, Placebo-Controlled Feasibility Study
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.
Read the 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.
- Being tested
- Atomoxetine 80 MG
- Keywords
- PTSD, ADHD, Atomoxetine, Combat Trauma, Cognitive Deficit
- Medical subject headings
- Stress Disorders, Post-Traumatic, Attention Deficit Disorder with Hyperactivity, Cognition Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Atomoxetine 80 MGDrug
Also called Strattera
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.
| Study group | Role | What they receive |
|---|---|---|
| Atomoxetine 80mg | Active comparator | 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 Receives: Drug: Atomoxetine 80 MG |
| Placebo | Placebo comparator | A pharmaceutically inert substance, which will be given to group one in their second phase and group tow in first phase. Receives: Drug: Atomoxetine 80 MG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Conners' Adult ADHD Rating Scales-Self-Report: Short Version (CAARS-S:S, Conner et al, 1999)
Conners' Adult ADHD Rating Scales-Self-Report: Short Version (CAARS-S:S, Conner et al, 1999): The CAARS-S:S is a 26-item questionnaire that assesses symptoms of ADHD in persons aged 18 years or older. T-scores above 65 indicate a likelihood of moderate to severe ADHD symptoms and impairment. The range for the CAARS-S:S is from 0 to 78. A score of 78 would resemble the worst symptoms of ADHD with a score 0 having no symptoms.
Measured: Visit 1, (Day1), Visit 4(Day 36), Visit 7 (Day 71)
The Adult ADHD Quality of Life-29 (AAQOL-29, Brod et al, 2006)
The Adult ADHD Quality of Life-29 (AAQOL-29, Brod et al, 2006): AAQoL-29 is a 29-item questionnaire designed to assess quality of life and was a secondary efficacy measure in this trial. It is a participant-reported outcome measure used to examine disease specific functional impairments and quality of life for adults with ADHD. The AAQoL is scored as an overall total score, measuring Life Productivity, Psycholofical Health, Relationship, and Life Outlook. Each item is rated by patients on a 5-point Likert scale ranging from "Not at all/Never" (1) to "Extremely/Very Often" (5). To derive overall scores, item scores are transformed to a 0-100-point scale (1=0; 2=25; 3=50; 4=75; 5=100). Then, the item scores are summed up and divided by item count to generate overall scores. The score range from 0 to 100. A higher score indicates greater QoL and better functioning.
Measured: Visit 1 (Day1), 4(Day 36), 7 (Day 71)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2014 (estimated)
- Study start15 Oct 2014
- Primary completion2 Mar 2017
- Study completion14 Apr 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Post Traumatic Stress DisorderStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- A small prospective, 10-week, fixed-dose, randomized, double-blind, placebo-controlled, and cross-over trial of atomoxetine as an add-on medication to other therapies in Veterans with comorbid ADHD/PTSD.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Zhewu Wang, MD, Principal investigator, Ralph H. Johnson VA Medical Center, Charleston, SC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02287038
- Sponsor's protocol ID
- D1725-P
- Other IDs
- I01BX007080
- Status last verified
- Mar 2019
- First submitted
- 3 Oct 2014
- Last updated
- 3 Apr 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 35312136
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Atomoxetine in Comorbid ADHD/PTSD: A Pilot, Placebo-Controlled Feasibility Study
- ClinicalTrials.gov ID
- NCT02287038
- Acronym / sponsor ID
- D1725-P
- Keywords
- PTSD, ADHD, Atomoxetine, Combat Trauma, Cognitive Deficit
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 15 Oct 2014 (actual)
- Primary completion
- 2 Mar 2017 (actual)
- Study completion
- 14 Apr 2017 (actual)
- First posted
- 10 Nov 2014 (estimated)
- Results
- Posted 3 Apr 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- A small prospective, 10-week, fixed-dose, randomized, double-blind, placebo-controlled, and cross-over trial of atomoxetine as an add-on medication to other therapies in Veterans with comorbid ADHD/PTSD.
| Arm | Type | Receives |
|---|---|---|
| Atomoxetine 80mg | Active comparator | Drug: Atomoxetine 80 MGAtomoxetine (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 |
| Placebo | Placebo comparator | Drug: Atomoxetine 80 MGA pharmaceutically inert substance, which will be given to group one in their second phase and group tow in first phase. |
Who may qualify
- Ages
- 20 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Veterans age 20 to 60 with PTSD and significant ADHD symptoms (CAARS-S:S > 65);
- Good physical health.
- Evidence of combat as defined by:
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Atomoxetine 80 MGAlso: StratteraSubjects 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. | Drug | Atomoxetine 80mg, Placebo |
Primary outcome
Conners' Adult ADHD Rating Scales-Self-Report: Short Version (CAARS-S:S, Conner et al, 1999)
Time frame: Visit 1, (Day1), Visit 4(Day 36), Visit 7 (Day 71)
Conners' Adult ADHD Rating Scales-Self-Report: Short Version (CAARS-S:S, Conner et al, 1999): The CAARS-S:S is a 26-item questionnaire that assesses symptoms of ADHD in persons aged 18 years or older. T-scores above 65 indicate a likelihood of moderate to severe ADHD symptoms and impairment. The range for the CAARS-S:S is from 0 to 78. A score of 78 would resemble the worst symptoms of ADHD with a score 0 having no symptoms.
The Adult ADHD Quality of Life-29 (AAQOL-29, Brod et al, 2006)
Time frame: Visit 1 (Day1), 4(Day 36), 7 (Day 71)
The Adult ADHD Quality of Life-29 (AAQOL-29, Brod et al, 2006): AAQoL-29 is a 29-item questionnaire designed to assess quality of life and was a secondary efficacy measure in this trial. It is a participant-reported outcome measure used to examine disease specific functional impairments and quality of life for adults with ADHD. The AAQoL is scored as an overall total score, measuring Life Productivity, Psycholofical Health, Relationship, and Life Outlook. Each item is rated by patients on a 5-point Likert scale ranging from "Not at all/Never" (1) to "Extremely/Very Often" (5). To derive overall scores, item scores are transformed to a 0-100-point scale (1=0; 2=25; 3=50; 4=75; 5=100). Then, the item scores are summed up and divided by item count to generate overall scores. The score range from 0 to 100. A higher score indicates greater QoL and better functioning.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35312136Wang 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.
- Individual participant dataSharing planned: No
Related trials for Post Traumatic Stress Disorder
Not yet recruiting
Magnetoencephalographic Correlates of Clinical Change After Cognitive Processing Therapy in Adults With PTSD
Trauma, Psychological, Traumatic Stress Disorder
Not yet recruiting
Deaf CBT-TS to Reduce Suicide Risk
Depression - Major Depressive Disorder, Anxiety
Recruiting
Restorative Early Sleep Treatment After the Emergency Department
Insomnia, Nightmares Associated With Trauma and Stress
Recruiting
Virtual Reality Assisted Trauma Focused CBT
PTSD - Post Traumatic Stress Disorder
Recruiting
Deep Brain Reorienting in Post-traumatic Stress Disorder
PTSD, Post-traumatic Stress Disorder
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zhewu Wang, MD principal investigator
Ralph H. Johnson VA Medical Center, Charleston, SC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Atomoxetine 80 MG in people with Post Traumatic Stress Disorder and Attention Deficit Hyperactivity Disorder, run by VA Office of Research and Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Conners' Adult ADHD Rating Scales-Self-Report: Short Version (CAARS-S:S, Conner et al, 1999) (time frame: Visit 1, (Day1), Visit 4(Day 36), Visit 7 (Day 71)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02287038, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Apr 2019.