Clinical trial NCT06412757: Silexan in the Treatment of Posttraumatic Stress Disorder Trial
Official title: Silexan in the Treatment of Posttraumatic Stress Disorder (STOP) Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Post Traumatic Stress Disorder
Keywords: posttraumatic stress disorder
adjunctive treatment
Silexan
phytoceutical
pharmacotherapy
randomized controlled trial
Lead sponsor: Deakin University
Sponsor class: OTHER
Collaborators: name: University of Melbourne
name: Ramsay Clinic Albert Road
First posted: 2024-05-14
Enrollment: 224
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The trial is a phase 3, 12-week, parallel-arm, randomized, placebo-controlled, double-blind trial. Participants will be randomly allocated to receive either (a) Silexan 160 mg or (b) an identical appearing inert placebo, daily for 12 weeks in addition to their usual prescribed medications.
Primary purpose: TREATMENT

Brief summary: Posttraumatic stress disorder (PTSD) is a common and debilitating mental illness. Current treatments for PTSD include psychotherapy and antidepressant medications. Many patients are unable to tolerate psychotherapy for PTSD and drop out of it. In addition, its effectiveness is limited. Up to 50 percent of patients who receive psychotherapy do not benefit from it. Antidepressant medications have only small benefits in PTSD. They also have unpleasant side effects that can make patients unwilling to take them. There is an urgent need to develop new treatments for PTSD that work and are well-tolerated. Silexan has the potential to provide an important alternative treatment for PTSD.

Silexan is derived from lavender oil. It is taken orally in the form of capsules. It is currently available over-the-counter in 14 countries, including Australia and the United States. Previous research has shown that it is an effective treatment for anxiety disorders, including Generalized Anxiety Disorder. It is also well-tolerated by patients. The only side effects that have been identified so far are mild gastrointestinal symptoms (including burping and breath odour) and these are uncommon. The results of a small pilot study suggest that Silexan may also be effective and well-tolerated in PTSD.

The STOP trial is a clinical trial that aims to investigate whether adding Silexan to treatment-as-usual improves PTSD symptoms in adults with PTSD. The trial will recruit 224 participants. Participants will be randomly assigned to take Silexan or a placebo (look-alike dummy pills) daily in addition to their usual medications for 12 weeks. The severity of their PTSD symptoms will be assessed prior to and at the end of this 12-week period.

The STOP trial has the potential to obtain definitive evidence regarding whether Silexan helps treat symptoms of PTSD. If Silexan is found to be an effective treatment for PTSD, the pool of patients who could potentially benefit from this treatment includes any adults with PTSD. Silexan is already available over-the-counter at a relatively low cost so there will be few barriers to accessing this treatment.

Detailed description: Background: Posttraumatic stress disorder (PTSD) is a common and debilitating psychiatric disorder. Existing PTSD treatments have very significant limitations. Current evidence-based treatments for PTSD include trauma-focussed psychotherapy and antidepressant medications, including selective serotonin reuptake inhibitors and the serotonin noradrenaline reuptake inhibitor venlafaxine. Many patients are unable to tolerate trauma-focussed psychotherapy. Uptake is relatively low and dropout rates are high. In addition, up to 50% of patients fail to respond to this therapy. Antidepressant medications have small clinical effects and are associated with unpleasant side effects that can lead to non-adherence. There is an urgent need for new treatments for PTSD that are effective and well-tolerated. Silexan has the potential to provide a transformative alternative to these treatments. It is an orally administered lavender oil preparation whose main constituents are the monoterpenoids linalool and linalyl acetate. It is available over-the-counter in 14 countries, including Australia and the United States. It has a novel pharmacodynamic profile that includes potent inhibition of voltage-gated calcium channels and reduction of serotonin 1A receptor binding potential. Silexan is an effective treatment for Generalized Anxiety Disorder (GAD) and other anxiety disorders. A 2019 independent meta-analysis of data from five randomized controlled trials involving 1,320 participants with anxiety disorders found that Silexan 160 mg out-performed paroxetine and lorazepam in reducing anxiety symptoms. Silexan is also well-tolerated. The only adverse effects that have been identified so far are mild gastrointestinal symptoms and these are uncommon. Promising pilot data suggest that Silexan may also be effective and well-tolerated in PTSD.

Hypothesis: The primary hypothesis is that Silexan, as an adjunct to treatment-as-usual, over 12 weeks will be superior to placebo in improving PTSD symptoms in adults with PTSD.

Specific aims: The trial aims to investigate the effectiveness of adjunctive Silexan, compared with placebo, over 12 weeks in improving PTSD symptoms. The primary outcome measure will be the between-group change from baseline in the total symptom severity score on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5).

Study design: The trial is a phase 3, 12-week, multi-site, parallel-arm, randomized, placebo-controlled, double-blind trial. Participants will be adults with PTSD without comorbid psychosis, bipolar disorder, moderate or severe substance use disorder or Borderline Personality Disorder. Participants randomized to the Silexan arm will receive Silexan 160 mg daily for 12 weeks in addition to their usual prescribed medications. Participants randomized to the placebo arm will receive capsules containing an inert placebo. The target sample size will be 156 participants, or 78 per arm. The study will recruit 224 participants to account for a 30% drop-out rate.

Clinical impact: There is an urgent need to develop new treatments for PTSD that are effective and well-tolerated. This trial has the potential to provide definitive evidence of the efficacy of Silexan in adult PTSD. Silexan is safe, well-tolerated, currently available and affordable, facilitating a rapid translation into clinical care. If Silexan is found to be an effective treatment for PTSD, the pool of patients who could potentially benefit from this treatment includes any adults with PTSD.

Eligibility criteria: Inclusion Criteria:

1. Aged 18 years or over.
2. Fluent in English.
3. Meet DSM-5 criteria for PTSD, irrespective of occupation (e.g. first responder, police officer, ex-military or civilian), determined using the Mini International Neuropsychiatric Interview 7.0.2.
4. Have a score on the PTSD Checklist for DSM-5 (PCL-5) equal to or over 33.

Exclusion Criteria:

1. Are currently serving in the Australian Defence Force
2. Lifetime history of a psychotic or bipolar disorder, or dissociative identity disorder.
3. Moderate or severe alcohol or other substance use disorder within 3 months of screening.
4. Active suicidal or homicidal ideation.
5. Borderline Personality Disorder (BPD).
6. Acute or unstable medical illness or other significant medical condition, that would make participation in the trial unsafe or inappropriate.
7. Pregnancy, lactation or unwillingness to use an acceptable method of contraception (required for both males and females who are of reproductive potential and sexually active with partners of the opposite sex) through the duration of participants' involvement in the study up to and including week 16. Participants will also be advised not to donate eggs or sperm during the study period.
8. Commencement of a trauma-focussed psychotherapy (including Prolonged Exposure, Cognitive Processing Therapy and Eye Movement Desensitisation and Reprocessing) within 3 months of screening.
9. Commencement or change in dose of psychoactive medications within 4 weeks of screening.
10. Participants will be asked not to initiate psychotherapy or change the dose of psychoactive medications during the course of the study except in clinically urgent circumstances; if this becomes necessary, a decision will be made on a case-by-case basis with regard to retaining the participant or terminating their participation.
11. Severe acquired brain injury.
12. Individual is not eligible for public mental health services due to their visa status in Australia or for any other reason.
13. Any other condition that in the opinion of the research team is likely to make completion of the trial requirements infeasible.
14. Inability to understand or speak English to the extent necessary to give informed consent and complete the trial (researcher or clinician-determined).

Primary outcomes:
measure: Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
timeFrame: At baseline and at week 12 of the study period
Secondary outcomes:
measure: Hamilton Anxiety Rating Scale (HAM-A)
timeFrame: At baseline, at week 12 and at week 16 of the study period
measure: Generalized Anxiety Disorder-7 (GAD-7)
timeFrame: At baseline, at week 12 and at week 16 of the study period
measure: Generalized Anxiety Disorder-7 (GAD-7)
timeFrame: At baseline, week 4, week 8 and week 12 of the study period
measure: Beck Depression Inventory-II (BDI-II)
timeFrame: At baseline, at week 12 and at week 16 of the study period
measure: Patient Health Questionnaire-9 (PHQ-9)
timeFrame: At baseline, at week 12 and at week 16 of the study period
measure: Patient Health Questionnaire-9 (PHQ-9)
timeFrame: At baseline, week 4, week 8 and week 12 of the study period
measure: Patient Health Questionnaire-15 (PHQ-15)
timeFrame: At baseline, at week 12 and at week 16 of the study period
measure: Patient Health Questionnaire-15 (PHQ-15)
timeFrame: At baseline, week 4, week 8 and week 12 of the study period
measure: Pittsburgh Sleep Quality Index, with Addendum for PTSD (PSQI & PSQI-A)
timeFrame: At baseline, at week 12 and at week 16 of the study period
measure: Pittsburgh Sleep Quality Index, with Addendum for PTSD (PSQI & PSQI-A)
timeFrame: At baseline, week 4, week 8 and week 12 of the study period
measure: Alcohol Use Disorders Identification Test (AUDIT)
timeFrame: At baseline, at week 12 and at week 16 of the study period
measure: Alcohol Use Disorders Identification Test (AUDIT)
timeFrame: At baseline, week 4, week 8 and week 12 of the study period
measure: World Health Organization (WHO) Disability Assessment Schedule (WHODAS 2.0)
timeFrame: At baseline, at week 12 and at week 16 of the study period
measure: General Well Being Schedule (GWBS)
timeFrame: At baseline, at week 12 and at week 16 of the study period
measure: Assessment of Quality of Life-6D (AQoL-6D)
timeFrame: At baseline, at week 12 and at week 16 of the study period
measure: PTSD Checklist for DSM-5 (PCL-5)
timeFrame: At intake, at week 12 and at week 16 of the study period
measure: PTSD Checklist for DSM-5 (PCL-5)
timeFrame: At intake, week 2, week 4, week 6, week 8 and week 12 of the study period
measure: Patient Global Impression of Change Scale (PGIC)
timeFrame: Week 2, week 4, week 6, week 8 and week 12 of the study period
measure: Actigraphy watches
timeFrame: Continously from baseline until week 16 of the study period
Other outcomes:
measure: Mediators of response to Silexan
timeFrame: Baseline
Locations:
city: Carlton
country: Australia
facility: University of Melbourne
state: Victoria
city: Geelong
country: Australia
facility: Deakin University
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Melbourne
country: Australia
facility: Ramsay Clinic Albert Road
state: Victoria
Study officials:
affiliation: Deakin University
name: Michael Berk, PhD
role: PRINCIPAL_INVESTIGATOR
References: