Post Traumatic Stress DisorderPhase 2NCT02934932
A Pilot Dose-Response Biomarker Study of Brexpiprazole Treatment in PTSD
A Phase 2 study testing Brexpiprazole in people with Post Traumatic Stress Disorder, run by Duke University at 1 site in United States.
Trial summary
Determine if brexpiprazole treatment will be associated with a dose-dependent reduction in resting pupil diameter as a reflection of locus coeruleus (LC) norepinephrine (NE) neuron target engagement in a group of subjects with PTSD. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Post Traumatic Stress Disorder
- What is being tested?
- Brexpiprazole
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Apr 2017to 30 Apr 2018
- Phase
- Phase 2
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants will be 18-65 years of age.
- All subjects will be evaluated by physical examination, ECG, standard blood chemistry, hematologic labs, toxicology testing, and urinalysis at baseline and end of study. Results of these studies must demonstrate a lack of clinically significant abnormalities prior to enrollment. If results are outside of the normal reference range the study physician will be consulted to assess if clinically significant.
- Subjects will need to satisfy DSM-5 criteria for PTSD and receive a CAPS-5 score of 40 or greater on testing for study enrollment.
- Subjects will need to be free of psychotropic medications or treatments that could impact results of this study as deemed by the PI for at least 1 week.
- If the subject's primary psychiatrist or treating primary care physician are providing the subject with psychotropic medications they will be notified and a discussion about tapering current psychotropic medications prior to study enrollment will occur.
Who cannot join
- Subjects will be excluded if they have significant medical or neurologic conditions (other than mild to moderate TBI), specifically seizures, or movement disorders,
- have substance abuse within 12 months of study enrollment, substance dependence within past three months, per DSM-5 criteria (excluding caffeine and nicotine). The absence of substance use will be determined by self-report and confirmed by the results of urine toxicology at screening.
- Women who are pregnant, breast-feeding, or planning to become pregnant while enrolled in this study will also be excluded.
- Subjects with a history of severe drug allergy or hypersensitivity, or known hypersensitivity to the Brexpiprazole or its ingredients.
- The subject has a history of tardive dyskinesia.
- The subject has clinically significant extrapyramidal symptoms (EPS) including akathisia.
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- The subject has epilepsy or a history of seizures, except for a single seizure episode (e.g., childhood febrile seizure, post traumatic, or alcohol withdrawal).
- The subject has chronic, uncontrolled, or unstable clinically relevant medical conditions Including:
- Uncontrolled hypertension defined as blood pressure greater than 180/90
- Hypotension defined as a blood pressure less than 90/60
- Moderate to severe hepatic impairment (Child-Pugh score ≥7)
- Moderate, Severe or End-Stage Renal Impairment (CrCL <60ml/min)
- Known CYP2DG Poor Metabolizers
- Heart failure NYHA Class III or IV
- Diabetes mellitus or HbA1c greater than 5.7% (which defines pre-diabetes)
- Hypertriglyceridemia defined as triglycerides greater than 200mg/dL
- Low white blood cell count (below lower range of normal)
- History of leukopenia or neutropenia
- Arrhythmia with heart rate greater than 100bpm
- Myocardial infarction in the past 6 months
- Cerebrovascular accident in the past 6 months
- Recurrent syncope
- Seizure disorder
- Currently receiving treatment for malignancy
- QTc interval of greater than 450ms on electrocardiogram
- The subject has a neurodegenerative disorder (Alzheimer disease, Parkinson's disease, multiple sclerosis, Huntington disease, etc.).
Trial locations and contacts
1 site in 1 country.
About this study
Determine if brexpiprazole treatment will be associated with a dose-dependent reduction in resting pupil diameter as a reflection of locus coeruleus (LC) norepinephrine (NE) neuron target engagement in a group of subjects with PTSD. All subjects will be evaluated by physical examination, ECG, standard blood chemistry, hematologic labs, toxicology testing, and urinalysis. Results of these studies must demonstrate a lack of clinically significant abnormalities prior to enrollment. Subjects will need to satisfy DSM-5 criteria for PTSD and receive a CAPS-5 score of 40 or greater on testing for study enrollment. Resting pupil diameter during pupillometric evaluation after two weeks on each treatment will serve as the primary outcome measure. This will be compared in the treatment groups using mixed effects repeated measures models to evaluate if there is a significant difference in pupil size among the treatments studied. As a secondary analysis this approach will be used to evaluate whether there is treatment effect on total CAPS-5 score. Lastly, the investigators will compute correlations between pupil size and CAPS-5 scores.
Read the detailed description
Primary Hypothesis: Brexpiprazole treatment will be associated with dose-dependent reduction in resting pupil diameter as a reflection of LC NE neuron target engagement in a group of subjects with PTSD. Secondary Hypothesis: Brexpiprazole therapy will be associated with a dosedependent decrease in CAPS-5 scores Tertiary Hypothesis: The pre-post treatment change in resting pupil diameter will be statistically significantly correlated with the pre-post change in CAPS-5 score.
Subjects will be screened and will undergo pupil measures with rating scales on Visit 1. Subject must be free of all psychotropic medications for one week before Day 1 assessment, except that prior FLX treatment will require 4 weeks of abstinence, and MAOIs will require 2 weeks of abstinence. They will be randomized to study drug an issued six weeks of study medication on Day 1 to take home. A phone call will then occur for safety assessment and medication adherence at every week. They will present back to the study site on Day 42 and undergo pupil measures with rating scales. They will then undergo a one week washout period. On Day 49 they will then be given another study drug to take home with rating scales and pupil measures obtained that day. A phone call will then occur for safety assessment and medication adherence at every week. They will present back to the study site on Day 91 and undergo pupil measures with rating scales. They will then undergo a one week washout period. On Day 98 they will then be given another study drug to take home with rating scales and pupil measures obtained that day. A phone call will then occur for safety assessment and medication adherence at every week. They will present back to the study site on Day 140 and undergo pupil measures with rating scales. No more study medication will be provide on Day 140 and a final visit will be scheduled for on Day 147, one week later, for and end of study interview with labs and physical exam. At each visit, other than the final visit, subjects will complete the CAPS-5, MADRS, Insomnia Severity Index, and Clinician Assessment for Adverse Effects.
- Conditions
- Post Traumatic Stress Disorder
- Being tested
- Brexpiprazole
- Medical subject headings
- Stress Disorders, Post-Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BrexpiprazoleDrug
Also called Rexulti
Comparison of brexpiprazole 2mg to placebo Comparison of brexpiprazole 4mg to placebo
| Study group | Role | What they receive |
|---|---|---|
| Brexpiprazole 2mg | Experimental | Subjects will be titrated to this dose of brexpiprazole for 6 weeks. Receives: Drug: Brexpiprazole |
| Brexpiprazole 4mg | Experimental | Subjects will be titrated to this dose of brexpiprazole for 6 weeks. Receives: Drug: Brexpiprazole |
| Placebo | Placebo comparator | Subjects will be titrated to this dose of placebo for 6 weeks. Receives: Drug: Brexpiprazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Resting Pupil Diameter
Evaluate the effects of two doses of brexpiprazole on locus coeruleus (LC) norepinephrine (NE) neuron activity.
Measured: Baseline to 6 weeks for each treatment arm
Secondary outcomes (1)
Change in CAPS-5 Ratings Score
Determine the effect of brexpiprazole therapy on PTSD symptom severity
Measured: Baseline to 6 weeks for each treatment arm
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2016 (estimated)
- Study start25 Apr 2017
- Primary completion30 Apr 2018
- Study completion30 Apr 2018
Why it stopped: Terminated due to slow enrollment.
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.
- Other trials for Post Traumatic Stress DisorderStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- Otsuka America Pharmaceutical
- Responsible party
- Sponsor
- Investigators
- Steven T Szabo, MD, PhD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02934932
- Sponsor's protocol ID
- Pro00071923
- Status last verified
- Feb 2019
- First submitted
- 14 Oct 2016
- Last updated
- 5 Mar 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Dose-Response Biomarker Study of Brexpiprazole Treatment in PTSD
- ClinicalTrials.gov ID
- NCT02934932
- Acronym / sponsor ID
- Pro00071923
- Conditions
- Post Traumatic Stress Disorder
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated due to slow enrollment.
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- Otsuka America Pharmaceutical
- Study start
- 25 Apr 2017 (actual)
- Primary completion
- 30 Apr 2018 (actual)
- Study completion
- 30 Apr 2018 (actual)
- First posted
- 17 Oct 2016 (estimated)
- Results
- Posted 5 Mar 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Determine if brexpiprazole treatment will be associated with a dose-dependent reduction in resting pupil diameter as a reflection of locus coeruleus (LC) norepinephrine (NE) neuron target engagement in a group of subjects with PTSD. All subjects will be evaluated by physical examination, ECG, standard blood chemistry, hematologic labs, toxicology testing, and urinalysis. Results of these studies must demonstrate a lack of clinically significant abnormalities prior to enrollment. Subjects will need to satisfy DSM-5 criteria for PTSD and receive a CAPS-5 score of 40 or greater on testing for study enrollment. Resting pupil diameter during pupillometric evaluation after two weeks on each treatment will serve as the primary outcome measure. This will be compared in the treatment groups using mixed effects repeated measures models to evaluate if there is a significant difference in pupil size among the treatments studied. As a secondary analysis this approach will be used to evaluate whether there is treatment effect on total CAPS-5 score. Lastly, the investigators will compute correlations between pupil size and CAPS-5 scores.
Detailed description
Primary Hypothesis: Brexpiprazole treatment will be associated with dose-dependent reduction in resting pupil diameter as a reflection of LC NE neuron target engagement in a group of subjects with PTSD. Secondary Hypothesis: Brexpiprazole therapy will be associated with a dosedependent decrease in CAPS-5 scores Tertiary Hypothesis: The pre-post treatment change in resting pupil diameter will be statistically significantly correlated with the pre-post change in CAPS-5 score.
Subjects will be screened and will undergo pupil measures with rating scales on Visit 1. Subject must be free of all psychotropic medications for one week before Day 1 assessment, except that prior FLX treatment will require 4 weeks of abstinence, and MAOIs will require 2 weeks of abstinence. They will be randomized to study drug an issued six weeks of study medication on Day 1 to take home. A phone call will then occur for safety assessment and medication adherence at every week. They will present back to the study site on Day 42 and undergo pupil measures with rating scales. They will then undergo a one week washout period. On Day 49 they will then be given another study drug to take home with rating scales and pupil measures obtained that day. A phone call will then occur for safety assessment and medication adherence at every week. They will present back to the study site on Day 91 and undergo pupil measures with rating scales. They will then undergo a one week washout period. On Day 98 they will then be given another study drug to take home with rating scales and pupil measures obtained that day. A phone call will then occur for safety assessment and medication adherence at every week. They will present back to the study site on Day 140 and undergo pupil measures with rating scales. No more study medication will be provide on Day 140 and a final visit will be scheduled for on Day 147, one week later, for and end of study interview with labs and physical exam. At each visit, other than the final visit, subjects will complete the CAPS-5, MADRS, Insomnia Severity Index, and Clinician Assessment for Adverse Effects.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Brexpiprazole 2mg | Experimental | Drug: BrexpiprazoleSubjects will be titrated to this dose of brexpiprazole for 6 weeks. |
| Brexpiprazole 4mg | Experimental | Drug: BrexpiprazoleSubjects will be titrated to this dose of brexpiprazole for 6 weeks. |
| Placebo | Placebo comparator | Drug: BrexpiprazoleSubjects will be titrated to this dose of placebo for 6 weeks. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Participants will be 18-65 years of age.
- All subjects will be evaluated by physical examination, ECG, standard blood chemistry, hematologic labs, toxicology testing, and urinalysis at baseline and end of study. Results of these studies must demonstrate a lack of clinically significant abnormalities prior to enrollment. If results are outside of the normal reference range the study physician will be consulted to assess if clinically significant.
- Subjects will need to satisfy DSM-5 criteria for PTSD and receive a CAPS-5 score of 40 or greater on testing for study enrollment.
- Subjects will need to be free of psychotropic medications or treatments that could impact results of this study as deemed by the PI for at least 1 week.
- If the subject's primary psychiatrist or treating primary care physician are providing the subject with psychotropic medications they will be notified and a discussion about tapering current psychotropic medications prior to study enrollment will occur.
Key exclusion criteria (26 listed)
- Subjects will be excluded if they have significant medical or neurologic conditions (other than mild to moderate TBI), specifically seizures, or movement disorders,
- have substance abuse within 12 months of study enrollment, substance dependence within past three months, per DSM-5 criteria (excluding caffeine and nicotine). The absence of substance use will be determined by self-report and confirmed by the results of urine toxicology at screening.
- Women who are pregnant, breast-feeding, or planning to become pregnant while enrolled in this study will also be excluded.
- Subjects with a history of severe drug allergy or hypersensitivity, or known hypersensitivity to the Brexpiprazole or its ingredients.
- The subject has a history of tardive dyskinesia.
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 |
|---|---|---|
| BrexpiprazoleAlso: RexultiComparison of brexpiprazole 2mg to placebo Comparison of brexpiprazole 4mg to placebo | Drug | Brexpiprazole 2mg, Brexpiprazole 4mg, Placebo |
Primary outcome
Change in Resting Pupil Diameter
Time frame: Baseline to 6 weeks for each treatment arm
Evaluate the effects of two doses of brexpiprazole on locus coeruleus (LC) norepinephrine (NE) neuron activity.
1 secondary outcome
Change in CAPS-5 Ratings Score
Time frame: Baseline to 6 weeks for each treatment arm
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Steven T Szabo, MD, PhD principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Brexpiprazole in people with Post Traumatic Stress Disorder, run by Duke University 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 5 inclusion and 26 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: stopped early, as of the sponsor's last update on 5 Mar 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 5 Mar 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?
Change in Resting Pupil Diameter (time frame: Baseline to 6 weeks for each treatment arm). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Mar 2019.