New Treatments for PTSD
Recruiting in Palo Alto (17 mi)
+6 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Global Coalition for Adaptive Research
Must not be taking: Psychiatric medications
Disqualifiers: Pregnancy, Suicide risk, Substance use, others
Prior Safety Data
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.
12345Is 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.
34567How 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.
89101112Eligibility 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.
+8 more
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
+16 more
Trial 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
Participant Groups
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.
8Treatment groups
Experimental Treatment
Placebo Group
Group I: Intervention D SLS-002Experimental Treatment1 Intervention
Group II: Intervention C DaridorexantExperimental Treatment1 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 VilazodoneExperimental Treatment1 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 HClExperimental Treatment1 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 PlaceboPlacebo Group1 Intervention
Group VI: Intervention C PlaceboPlacebo Group1 Intervention
A matching placebo will be administered at 50 mg daily in the same regimen as the intervention.
Group VII: Intervention A PlaceboPlacebo Group1 Intervention
A matching placebo will be administered at 10 to 60 mg daily in the same regimen as the intervention.
Group VIII: Intervention B PlaceboPlacebo Group1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Upstate Clinical Research Associates, LLCWilliamsville, NY
Advanced Discovery ResearchAtlanta, GA
Homestead Associates in Research, Inc.Miami, FL
Advanced Discovery ResearchDecatur, GA
More Trial Locations
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Who Is Running the Clinical Trial?
Global Coalition for Adaptive ResearchLead Sponsor
CitelineCollaborator
PPD DEVELOPMENT, LPIndustry Sponsor
CitelineIndustry Sponsor
U.S. Army Medical Research and Development CommandCollaborator
PPDIndustry Sponsor
Berry ConsultantsCollaborator
Idorsia Pharmaceuticals Ltd.Industry Sponsor
Cambridge Cognition LtdIndustry Sponsor
References
Pharmacological therapy for post-traumatic stress disorder: a systematic review and meta-analysis of monotherapy, augmentation and head-to-head approaches. [2023]Background: Pharmacological approaches are widely used for post-traumatic stress disorder (PTSD) despite uncertainty over efficacy. Objectives: To determine the efficacy of all pharmacological approaches, including monotherapy, augmentation and head-to-head approaches (drug versus drug, drug versus psychotherapy), in reducing PTSD symptom severity. Method: A systematic review and meta-analysis of randomised controlled trials were undertaken; 115 studies were included. Results: Selective serotonin reuptake inhibitors (SSRIs) were found to be statistically superior to placebo in reduction of PTSD symptoms but the effect size was small (standardised mean difference -0.28, 95% CI -0.39 to -0.17). For individual monotherapy agents compared to placebo in two or more studies, we found small statistically significant evidence for the antidepressants fluoxetine, paroxetine, sertraline, venlafaxine and the antipsychotic quetiapine. For pharmacological augmentation, we found small statistically significant evidence for prazosin and risperidone. Conclusions: Some medications have a small positive effect on reducing PTSD symptom severity and can be considered as potential monotherapy treatments; these include fluoxetine, paroxetine, sertraline, venlafaxine and quetiapine. Two medications, prazosin and risperidone, also have a small positive effect when used to augment pharmacological monotherapy. There was no evidence of superiority for one intervention over another in the small number of head-to-head comparison studies.
Treatment of posttraumatic stress disorder with nefazodone. [2019]Selective serotonin reuptake inhibitors are useful in the treatment of posttraumatic stress disorder (PTSD), but have a number of side-effects which limit their acceptability. A newer serotonergic compound, nefazodone, has a different side-effect profile, thus making it a potentially promising compound to study. Seventeen private practice patients with PTSD were treated with nefazodone up to 600 mg/day for a maximum total treatment period of 12 weeks. All subjects were civilians, and were monitored for efficacy and side-effects at weeks 1, 2, 4, 6, 8 and 12. Nefazodone was associated with statistically significant improvement in mean scores on all six rating scales used to assess change from baseline in PTSD symptoms. Additionally, statistically significant improvement from baseline were seen for the intrusive, avoidant/numbing, and hyperarousal clusters on a global PTSD scale. Early improvements in nightmares and general sleep disturbance were observed. Overall, there was a 43% response rate at endpoint, or 60% in treatment completers, by observer rating. Side-effects (assessed on the Medication Effects Scale) were generally benign. Nefazodone was associated with clinical improvement in this population, and now needs to be studied in double-blind, placebo controlled, protocols.
Patient and Clinical Factors Associated With Response to Medications for Posttraumatic Stress Disorder. [2022]Objective: Fluoxetine, paroxetine, sertraline, topiramate, and venlafaxine have previously shown efficacy for posttraumatic stress disorder (PTSD) in randomized clinical trials. Two prior studies using Department of Veterans Affairs (VA) medical records data show these medications are also effective in routine practice. Using an expanded retrospective cohort, we assessed the possibility of differential patterns of response based on patient and clinical factors.
A Double-Blind, Placebo-Controlled Randomized Trial of Vilazodone in the Treatment of Posttraumatic Stress Disorder and Comorbid Depression. [2022]To determine the efficacy, safety, and tolerability of vilazodone in the treatment of posttraumatic stress disorder (PTSD) with comorbid mild-to-moderate depression.
Comparing Medications for DSM-5 PTSD in Routine VA Practice. [2022]Fluoxetine, paroxetine, sertraline, topiramate, and venlafaxine have previously shown efficacy for posttraumatic stress disorder (PTSD). One prior study using US Department of Veterans Affairs (VA) medical records data to compare these agents found no differences in symptom reduction in clinical practice. The current study addresses several weaknesses in that study, including limited standardization of treatment duration, inability to account for prior treatment receipt, use of an outdated symptomatic assessment for PTSD, and lack of functional outcome.
Vilazodone (Viibryd)--a new antidepressant. [2022]Vilazodone (Viibryd--Forest), a selective serotonin reuptake inhibitor (SSRI) and partial 5-HT(1A) receptor agonist, has been approved by the FDA for treatment of depression. It has been claimed to have no sexual side effects and not to cause weight gain.
A 1-year, open-label study assessing the safety and tolerability of vilazodone in patients with major depressive disorder. [2022]Vilazodone, a selective serotonin (5-HT) reuptake inhibitor and 5-HT(1A) receptor partial agonist, was efficacious in two 8-week placebo-controlled studies in adults with major depressive disorder. This open-label, multicenter study assessed the long-term safety of vilazodone. Adult patients with a 17-item Hamilton Rating Scale for Depression score of 18 or greater received vilazodone according to a fixed-titration schedule to reach a dose of 40 mg/d continued up to 1 year. Safety assessments included adverse events (AEs), physical examinations, clinical chemistry, electrocardiograms, and the Changes in Sexual Functioning Questionnaire. Effectiveness was assessed with the Montgomery-Åsberg Depression Rating Scale and Clinical Global Impressions scales. The safety population comprised 599 patients; 254 patients completed 1 year of treatment. The most frequent AEs were diarrhea (35.7%), nausea (31.6%), and headache (20.0%); greater than 90% of these AEs were mild or moderate. Adverse events resulting in discontinuation in more than 1% of patients were nausea (1.3%) and diarrhea (1.2%). There were no clinically important changes in physical examinations, electrocardiograms, or clinical chemistries. Mean weight increased by 1.7 kg (observed cases). Changes in Sexual Functioning Questionnaire mean scores (observed cases) improved throughout treatment for both males and females. Montgomery-Åsberg Depression Rating Scale mean scores were 29.9 at baseline, 11.4 at week 8, and 7.1 at week 52 (observed cases). Vilazodone 40 mg/d for 1 year was safe and well tolerated by adults with major depressive disorder.
Seizure Reduction with Fluoxetine in Dravet Syndrome. [2021]An adult woman with Dravet syndrome (documented SCN1A mutation) experienced a marked reduction in seizures when treated with the selective serotonin reuptake inhibitor (SSRI) fluoxetine. The seizure reduction may be partly to reductions associated with aging in Dravet patients, but it appears to be due at least in part to the fluoxetine. A prior preliminary study reported that fenfluramine reduces seizures in patients with Dravet syndrome. Fenfluramine may produce this effect by increasing serotonin brain levels, and SSRIs have been found to possess antiepileptic properties in animal models of epilepsy. Given the known cardiac risks of fenfluramine, consideration of randomized clinical trials with SSRIs should be considered in Dravet syndrome and other epilepsies.
Pharmacogenomics and Efficacy of Risperidone Long-Term Treatment in Thai Autistic Children and Adolescents. [2022]The purpose of this study was to evaluate the association of pharmacogenomic factors and clinical outcome in autistic children and adolescents who were treated with risperidone for long periods. Eighty-two autistic subjects diagnosed with DSM-IV and who were treated with risperidone for more than 1 year were recruited. Pharmacogenomics and clinical outcome (CGI-I, aggressive, overactivity and repetitive score) were evaluated. Almost all patients showed stable symptoms on aggressive behaviour (89.02%), overactivity (71.95%), repetitive (70.89%) behaviour and all clinical symptoms (81.71%). Only 4.48% of patients showed minimally worse CGI-I score. Patients in the non-stable symptom group had DRD2 Taq1A non-wild-type (TT and CT) frequencies higher than the clinically stable group (p = 0.04), whereas other gene polymorphisms showed no significant association. Haplotype ACCTCAT (rs6311, rs1045642, rs1128503, rs1800497, rs4436578, rs1799978, rs6280) showed a significant association with non-stable clinical outcome (χ2  = 6.642, p = 0.010). Risperidone levels showed no association with any clinical outcome. On the other hand, risperidone dose, 9-OH risperidone levels and prolactin levels were significantly higher in the non-stable compared to the stable symptom group (p = 0.013, p = 0.044, p = 0.030). Increased appetite was the most common adverse drug reaction and associated with higher body-weight, whereas it was not significantly associated with genetic variations and non-genetic information. In conclusion, risperidone showed efficacy to control autism, especially aggressive symptoms in long-term treatment. However, Taq1A T - carrier of dopamine 2 receptor gene - is associated with non-stable response in risperidone-treated patients. This study supports pharmacogenomics testing for personalized therapy with risperidone in autistic children and adolescents.
Recent Advances in the Pharmacological Management of Behavioral Disturbances Associated with Autism Spectrum Disorder in Children and Adolescents. [2020]Autism spectrum disorder (ASD) is a heterogeneous neuropsychiatric condition affecting an estimated one in 36 children. Youth with ASD may have severe behavioral disturbances including irritability, aggression, and hyperactivity. Currently, there are only two medications (risperidone and aripiprazole) approved by the US Food and Drug Administration (FDA) for the treatment of irritability associated with ASD. Pharmacologic treatments are commonly used to target ASD-associated symptoms including irritability, mood lability, anxiety, and hyperactivity. However, evidence for the efficacy of many commonly used treatments is limited by the lack of large placebo-controlled trials of these medications in this population. Research into the pathophysiology of ASD has led to new targets for pharmacologic therapy including the neuroimmune system, the endocannabinoid system, and the glutamatergic neurotransmitter system. The goal of this review is to provide an overview of the current evidence base for commonly used treatments, as well as emerging treatment options for common behavioral disturbances seen in youth with ASD.
A head-to-head comparison of aripiprazole and risperidone for safety and treating autistic disorders, a randomized double blind clinical trial. [2022]Aripiprazole and risperidone are the only FDA approved medications for treating irritability in autistic disorder, however there are no head-to-head data comparing these agents. This is the first prospective randomized clinical trial comparing the safety and efficacy of these two medications in patients with autism spectrum disorders. Fifty nine children and adolescents with autism spectrum disorders were randomized to receive either aripiprazole or risperidone for 2 months. The primary outcome measure was change in Aberrant Behavior Checklist (ABC) scores. Adverse events were assessed. Aripiprazole as well as risperidone lowered ABC scores during 2 months. The rates of adverse effects were not significantly different between the two groups. The safety and efficacy of aripiprazole (mean dose 5.5 mg/day) and risperidone (mean dose 1.12 mg/day) were comparable. The choice between these two medications should be on the basis of clinical equipoise considering the patient's preference and clinical profile.
A Practical Guide to the Treatment of Dravet Syndrome with Anti-Seizure Medication. [2022]Dravet syndrome is a severe developmental and epileptic encephalopathy characterised by refractory seizures and cognitive dysfunction. The treatment is challenging, not least because the seizures are highly drug resistant, requiring multiple anti-seizure medications (ASMs), while some ASMs can exacerbate seizures. Initial treatments include the broad-spectrum ASMs valproate (VPA), and clobazam (CLB) in some regions; however, they are generally insufficient to control seizures. With this in mind, three adjunct ASMs have been approved specifically for the treatment of seizures in patients with Dravet syndrome: stiripentol (STP) in 2007 in the European Union and 2018 in the USA, cannabidiol (CBD) in 2018/2019 (in combination with CLB in the European Union) and fenfluramine (FFA) in 2020. These "add-on" therapies (mostly to VPA/CLB) are used as escalation therapies, with the choice dependent on availability in different countries, patient characteristics and caregiver preferences. Topiramate is also frequently used, with evidence of efficacy in Dravet syndrome, and there is anecdotal evidence of efficacy with bromide, which is frequently used in Germany and Japan. With a growing treatment landscape for Dravet syndrome, there can be practical challenges for clinicians, particularly with issues associated with polypharmacy. This practical guide provides an overview of these main ASMs including their indications/contraindications, mechanism of action, efficacy, safety and tolerability profile, dosage requirements, and laboratory and clinical parameters to be evaluated. Standard laboratory and clinical parameters include blood counts, liver function tests, serum concentrations of ASMs, monitoring the growth of children, as well as weight loss and acceleration of behavioural problems. Regular cardiac monitoring is also important with FFA as it has previously been associated with cases of cardiac valve disease when used in adults at high doses (up to 120 mg/day) in combination with phentermine as a therapy for obesity. Importantly, no signs of heart valve disease have been documented to date at the low doses used in patients with developmental and epileptic encephalopathies. In addition, potential drug-drug interactions and their consequences are a key consideration in everyday practice. Interactions that potentially require dosage adjustments to alleviate adverse events include the following: STP + CLB resulting in increased plasma concentrations of CLB and its active metabolite norclobazam may increase somnolence, and an interaction with STP and VPA may increase gastrointestinal adverse events. Cannabidiol has a bi-directional interaction with CLB producing an increase in plasma concentrations of 7-OH-CBD and norclobazam resulting in the potential for increased somnolence and sedation. In addition, CBD is associated with elevations of liver transaminases particularly in patients taking concomitant VPA. The interaction between FFA and STP requires a dose reduction of FFA. Furthermore, concomitant administration of VPA with topiramate has been associated with encephalopathy and/or hyperammonaemia. Finally, we briefly describe other ASMs used in Dravet syndrome, and current key clinical trials.