New Treatments for PTSD

Recruiting at 6 trial locations

Overseen By Please visit the website:

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Global Coalition for Adaptive Research

Must not be taking: Psychiatric medications

Disqualifiers: Pregnancy, Suicide risk, Substance use, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 12 weeks

800 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase 2 randomized, double-blinded, placebo-controlled study that will evaluate multiple potential pharmacotherapeutic interventions for PTSD utilizing an adaptive platform trial design. Participants are randomized among the multiple cohorts in the study and the resulting randomization enables sharing/pooling of control participants, where all interventions may be compared to a common control (placebo). This master protocol describes the default procedures and analyses for all cohorts; treatment-specific procedures will be described in the Master Protocol cohort-specific appendices. Individual cohorts may have additional eligibility requirements, safety and efficacy procedures, or endpoints, which will be described in corresponding intervention-specific clinicaltrials.gov records.

Do I have to stop taking my current medications for the trial?

Yes, you may need to stop taking certain medications. The trial requires a washout period (time without taking certain medications) of at least 14 days or 5 half-lives of the medication, whichever is longer, before starting the study treatment. Please check with the trial team for specific medication restrictions.

What data supports the effectiveness of the drug Daridorexant, Quviviq, Nemorexant, ACT-541468, Daridorexant hydrochloride, Fluoxetine HCl, Prozac, Sarafem, Fluoxetine Hydrochloride, Placebo, Control, Dummy Treatment, Vilazodone Hydrochloride, Viibryd for PTSD?

Research shows that fluoxetine, a component of the treatment, has a small positive effect on reducing PTSD symptoms compared to a placebo. Additionally, vilazodone has been studied for its efficacy in treating PTSD with comorbid depression. ^{1 2 3 4 5}

Is vilazodone safe for humans?

Vilazodone has been studied for its safety in humans, particularly in treating major depressive disorder. In a 1-year study, it was generally well tolerated, with common mild side effects like diarrhea, nausea, and headache. There were no significant changes in physical exams or heart tests, and most side effects were mild or moderate. ^{3 4 5 6 7}

How is the drug Daridorexant, Fluoxetine HCl, Vilazodone Hydrochloride unique for PTSD treatment?

This combination treatment for PTSD is unique because it includes Daridorexant, which is known for its role in sleep regulation, and Fluoxetine, an SSRI that has shown potential in reducing seizures in conditions like Dravet syndrome, suggesting a novel approach to managing PTSD symptoms through sleep and mood regulation. ^{8 9 10 11 12}

Eligibility Criteria

This trial is for US military service members or veterans aged 18-65 with PTSD diagnosed by DSM-5 criteria, having a CAPS-5-R score of ≥26. Participants must have experienced trauma over 3 months ago and agree to use approved birth control methods. Exclusions include heavy alcohol use, psychotic features, unmanaged sleep apnea, recent cancer treatment (except certain skin cancers), high suicide risk, pregnancy/breastfeeding, prohibited medication use without washout period compliance.

Inclusion Criteria

Participant agrees to consistently use an acceptable method of birth control throughout the study

For females of reproductive potential, acceptable birth control methods include hormonal contraceptives, intrauterine device, or double barrier contraception

I am using two forms of birth control.

Exclusion Criteria

My sleep apnea is currently not well-managed.

Participant has specific systolic or diastolic blood pressure measurements

Participant does not have a stable method of contact over the duration of the study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive pharmacotherapeutic interventions for PTSD over a 12-week period

12 weeks

Weekly visits (in-person or virtual)

Safety Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

Biomarker Extension

Testing in biomarker-defined cohorts for prospective evaluation of treatment

Treatment Details

Interventions

• Daridorexant
• Fluoxetine HCl
• Placebo
• Vilazodone Hydrochloride

Trial Overview The study tests Fluoxetine HCl, Daridorexant, Vilazodone HCl against placebos in a Phase 2 randomized double-blind setup. It's an adaptive platform trial where participants are assigned to cohorts; each cohort may have specific additional procedures or endpoints detailed in appendices.

Participant Groups

Group I: Intervention D SLS-002 Experimental Treatment 1 Intervention

Group II: Intervention C Daridorexant Experimental Treatment 1 Intervention

Daridorexant will be administered 50 mg once daily within 30 minutes of going to bed at least 2 hours after the last meal.

Group III: Intervention B Vilazodone Experimental Treatment 1 Intervention

Vilazodone HCl will be administered at 10 mg once daily for 7 days, followed by 20 mg for 7 days, followed by 40 mg for the remainder of the trial. There must be a minimum of 7 days between dosage increases. A televisit will be conducted by site personnel 1 week after each increase in dose to determine tolerability. One reduction in dose due to tolerability will be allowed. After Week 8, dose reduction for tolerability is allowed, but dose increase is not allowed.

Group IV: Intervention A: Fluoxetine HCl Experimental Treatment 1 Intervention

Fluoxetine will be administered at 10 to 60 mg daily. The initial dose for all subjects will be 10 mg daily for 1 week, then increased to 20 mg daily for 2 weeks, then increased to 40 mg daily for 2 weeks, then increased to 60 mg daily for the remainder of the trial. One reduction in dose due to tolerability will be allowed. When a subject's dose is decreased due to tolerability, the dose will not be increased.

Group V: Intervention D Placebo Placebo Group 1 Intervention

Group VI: Intervention C Placebo Placebo Group 1 Intervention

A matching placebo will be administered at 50 mg daily in the same regimen as the intervention.

Group VII: Intervention A Placebo Placebo Group 1 Intervention

A matching placebo will be administered at 10 to 60 mg daily in the same regimen as the intervention.

Group VIII: Intervention B Placebo Placebo Group 1 Intervention

A matching placebo will be administered at 10 to 40 mg daily in the same regimen as the intervention.

Daridorexant is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Quviviq for:

• Insomnia

Approved in European Union as Quviviq for:

• Insomnia

Approved in Canada as Quviviq for:

• Insomnia

Who Is Running the Clinical Trial?

Global Coalition for Adaptive Research

Lead Sponsor

Trials

7

Recruited

22,600+

Citeline

Collaborator

Trials

5

Recruited

1,600+

PPD DEVELOPMENT, LP

Industry Sponsor

Trials

167

Recruited

38,000+

David Simmons

PPD DEVELOPMENT, LP

Chief Executive Officer since 2012

BSc in Applied Science from Georgia Institute of Technology

Martina Flammer

PPD DEVELOPMENT, LP

Chief Medical Officer since 2024

MD

Citeline

Industry Sponsor

Trials

5

Recruited

1,600+

U.S. Army Medical Research and Development Command

Collaborator

Trials

296

Recruited

249,000+

PPD

Industry Sponsor

Trials

162

Recruited

36,600+

Dr. Austin Smith

PPD

Chief Medical Officer since 2020

Doctor of Medicine from the Royal College of Surgeons in Ireland

David Simmons

PPD

Chief Executive Officer since 2012

Bachelor’s degree in Applied Mathematics and Industrial Management from Carnegie Mellon University

Berry Consultants

Collaborator

Trials

16

Recruited

58,200+

Idorsia Pharmaceuticals Ltd.

Industry Sponsor

Trials

124

Recruited

36,400+

Antonio Olivieri

Idorsia Pharmaceuticals Ltd.

Chief Medical Officer since 2024

Not specified

André C. Muller

Idorsia Pharmaceuticals Ltd.

Chief Executive Officer

Not specified

Cambridge Cognition Ltd

Industry Sponsor

Trials

17

Recruited

4,700+

Findings from Research

Selective serotonin reuptake inhibitors (SSRIs) like fluoxetine, paroxetine, and sertraline show a statistically significant but small effect in reducing PTSD symptoms compared to placebo, based on a systematic review of 115 randomized controlled trials.

Prazosin and risperidone also demonstrate small positive effects when used to augment other treatments, but no single pharmacological intervention was found to be superior to others in head-to-head comparisons.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological therapy for post-traumatic stress disorder: a systematic review and meta-analysis of monotherapy, augmentation and head-to-head approaches. Hoskins, MD., Bridges, J., Sinnerton, R., et al.[2023]

In a study of 17 patients with PTSD treated with nefazodone for up to 12 weeks, significant improvements were observed in PTSD symptoms across all six rating scales, indicating its potential efficacy as a treatment.

Nefazodone demonstrated a 43% response rate overall, with side effects being generally mild, suggesting it may be a safer alternative to traditional selective serotonin reuptake inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of posttraumatic stress disorder with nefazodone. Davidson, JR., Weisler, RH., Malik, ML., et al.[2019]

In a study of 6,839 VA outpatients with PTSD, no significant differences in medication efficacy were found among fluoxetine, paroxetine, sertraline, topiramate, and venlafaxine, suggesting that these medications are similarly effective in real-world settings.

Patients with higher baseline PTSD checklist scores and those receiving evidence-based psychotherapy showed better improvement, while those with high disability levels were less likely to experience meaningful benefits, highlighting the importance of combined treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient and Clinical Factors Associated With Response to Medications for Posttraumatic Stress Disorder. Shiner, BR., Gui, J., Rozema, L., et al.[2022]

In a 12-week study involving 59 adult patients with PTSD and mild-to-moderate depression, vilazodone at a dose of 40 mg/day did not show significant improvement in PTSD symptoms compared to placebo.

Vilazodone was generally well tolerated, with no notable differences in adverse events between the vilazodone and placebo groups, indicating a favorable safety profile despite lack of efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Double-Blind, Placebo-Controlled Randomized Trial of Vilazodone in the Treatment of Posttraumatic Stress Disorder and Comorbid Depression. Ramaswamy, S., Driscoll, D., Reist, C., et al.[2022]

In a study of 834 VA outpatients with PTSD, venlafaxine was found to be significantly more effective than fluoxetine, paroxetine, sertraline, and topiramate in achieving remission of PTSD symptoms during the acute treatment phase.

Continuing medication during the continuation phase was associated with a lower risk of needing acute psychiatric services, highlighting the importance of ongoing treatment for managing PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing Medications for DSM-5 PTSD in Routine VA Practice. Shiner, B., Leonard, CE., Gui, J., et al.[2022]

Vilazodone is an FDA-approved medication for treating depression that works as both a selective serotonin reuptake inhibitor (SSRI) and a partial agonist at the 5-HT(1A) receptor, which may enhance its antidepressant effects.

It is reported to have a favorable side effect profile, claiming to avoid common issues associated with other antidepressants, such as sexual side effects and weight gain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vilazodone (Viibryd)--a new antidepressant. [2022]

Vilazodone, taken at a dose of 40 mg/day for up to 1 year, was found to be safe and well tolerated in a study of 599 adults with major depressive disorder, with most adverse events being mild or moderate.

The treatment significantly reduced depression symptoms, as shown by a decrease in Montgomery-Åsberg Depression Rating Scale scores from 29.9 at baseline to 7.1 at week 52, indicating its long-term efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 1-year, open-label study assessing the safety and tolerability of vilazodone in patients with major depressive disorder. Robinson, DS., Kajdasz, DK., Gallipoli, S., et al.[2022]

A woman with Dravet syndrome showed a significant reduction in seizures when treated with the SSRI fluoxetine, suggesting potential antiepileptic properties of SSRIs.

The findings support the idea that SSRIs like fluoxetine could be a safer alternative to fenfluramine, which has known cardiac risks, warranting further clinical trials for their use in treating Dravet syndrome and other forms of epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Seizure Reduction with Fluoxetine in Dravet Syndrome. Meador, KJ.[2021]

In a study of 82 autistic children and adolescents treated with risperidone for over a year, the majority showed stable symptoms, particularly in aggressive behavior (89.02% stability), indicating that risperidone is effective for long-term management of autism-related symptoms.

The presence of certain genetic variations (specifically the DRD2 Taq1A non-wild-type) was linked to a less stable clinical response to risperidone, suggesting that pharmacogenomic testing could help tailor treatment for better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacogenomics and Efficacy of Risperidone Long-Term Treatment in Thai Autistic Children and Adolescents. Nuntamool, N., Ngamsamut, N., Vanwong, N., et al.[2022]

Currently, only risperidone and aripiprazole are FDA-approved medications for treating irritability in children with autism spectrum disorder (ASD), highlighting a significant gap in effective pharmacological options for this population.

Research is exploring new treatment targets for ASD, including the neuroimmune system and the endocannabinoid system, which may lead to more effective therapies for managing symptoms like irritability and hyperactivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent Advances in the Pharmacological Management of Behavioral Disturbances Associated with Autism Spectrum Disorder in Children and Adolescents. Lamy, M., Pedapati, EV., Dominick, KL., et al.[2020]

In a clinical trial involving 59 children and adolescents with autism spectrum disorders, both aripiprazole and risperidone were effective in reducing irritability, as measured by the Aberrant Behavior Checklist (ABC) scores over 2 months.

The study found that the rates of adverse effects were similar for both medications, indicating that aripiprazole (mean dose 5.5 mg/day) and risperidone (mean dose 1.12 mg/day) have comparable safety profiles, allowing treatment choice to be based on patient preference and clinical considerations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A head-to-head comparison of aripiprazole and risperidone for safety and treating autistic disorders, a randomized double blind clinical trial. Ghanizadeh, A., Sahraeizadeh, A., Berk, M.[2022]

Dravet syndrome is a severe condition with drug-resistant seizures, and while initial treatments like valproate and clobazam are common, they often fail to control seizures, necessitating the use of adjunct anti-seizure medications (ASMs) such as stiripentol, cannabidiol, and fenfluramine, which have been specifically approved for this syndrome.

Clinicians face challenges with polypharmacy due to potential drug-drug interactions among ASMs, which can affect efficacy and safety; for example, stiripentol can increase the levels of clobazam, leading to increased sedation, while cannabidiol can elevate liver enzymes when used with valproate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Practical Guide to the Treatment of Dravet Syndrome with Anti-Seizure Medication. Strzelczyk, A., Schubert-Bast, S.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Pharmacological therapy for post-traumatic stress disorder: a systematic review and meta-analysis of monotherapy, augmentation and head-to-head approaches. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Treatment of posttraumatic stress disorder with nefazodone. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Patient and Clinical Factors Associated With Response to Medications for Posttraumatic Stress Disorder. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

A Double-Blind, Placebo-Controlled Randomized Trial of Vilazodone in the Treatment of Posttraumatic Stress Disorder and Comorbid Depression. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Comparing Medications for DSM-5 PTSD in Routine VA Practice. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Vilazodone (Viibryd)--a new antidepressant. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

A 1-year, open-label study assessing the safety and tolerability of vilazodone in patients with major depressive disorder. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Seizure Reduction with Fluoxetine in Dravet Syndrome. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Pharmacogenomics and Efficacy of Risperidone Long-Term Treatment in Thai Autistic Children and Adolescents. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Recent Advances in the Pharmacological Management of Behavioral Disturbances Associated with Autism Spectrum Disorder in Children and Adolescents. [2020]

11. United States pubmed.ncbi.nlm.nih.gov

A head-to-head comparison of aripiprazole and risperidone for safety and treating autistic disorders, a randomized double blind clinical trial. [2022]

12. New Zealand pubmed.ncbi.nlm.nih.gov

A Practical Guide to the Treatment of Dravet Syndrome with Anti-Seizure Medication. [2022]