ANZCTR - Registration

Reset your password and enable multi-factor authentication (MFA)

For ANZCTR account holders: to help ensure the cyber safety of your account, you’ll need to reset your password and set-up multi-factor authentication (MFA) as per the instructions below.

Go to the Login page, click ‘reset password’ and follow the instructions.
Check your email for the link to set a new password.
Create a new password that meets requirements.
Return to the Login page and enter your new password. A verification code will be sent to your email.
Check your email for the code and enter it on the Login page. If the code is entered incorrectly, you can re-enter the correct one or request a new one.

Learn more about MFA and its importance on the Australian Signals Directorate website.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers

Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06412757

Registration number

NCT06412757

Ethics application status

Date submitted

9/05/2024

Date registered

14/05/2024

Date last updated

25/03/2025

Titles & IDs

Public title

Silexan in the Treatment of Posttraumatic Stress Disorder Trial

Scientific title

Silexan in the Treatment of Posttraumatic Stress Disorder (STOP) Trial

Secondary ID [1]

HT9425-23-1-0885

Secondary ID [2]

29307

Universal Trial Number (UTN)

Trial acronym

STOP

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Post Traumatic Stress Disorder

Condition category

Condition code

Mental Health

Anxiety

Mental Health

Other mental health disorders

Mental Health

Depression

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Treatment: Drugs - Silexan
Other interventions - Placebo

Experimental: Silexan 160 mg - Participants in the Silexan arm will take Silexan 160 mg daily in the morning for 12 weeks in addition to their usual prescribed psychoactive medications. Participants will be followed up at 2, 4, 6, 8 and 12 weeks of the intervention period, as well as at 4 weeks post-treatment (off-treatment follow-up period).

Placebo comparator: Placebo - Participants in this arm will take two placebo capsules daily in the morning for 12 weeks in addition to their usual medications. Participants will be followed up at 2, 4, 6, 8 and 12 weeks of the intervention period, as well as at 4 weeks post-treatment (off-treatment follow-up period).

Treatment: Drugs: Silexan
Participants in the Silexan arm will take two over-encapsulated capsules, each containing 80 mg Silexan, daily orally in the morning in addition to their usual medications. No modifications of allocated interventions will be made for any trial participants; if appropriate (i.e following the emergence of adverse events) participants will be withdrawn from the intervention.

Other interventions: Placebo
Participants in the placebo arm will take two capsules containing an inert placebo daily orally in the morning in addition to their usual medications. The placebo capsules will contain a sub-therapeutic amount of lavender oil to mimic the odor of the experimental drug (Silexan).

Intervention code [1]

Treatment: Drugs

Intervention code [2]

Other interventions

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)

Assessment method [1]

The Primary Outcome Measure will be the between-group difference in the change from baseline to week 12 in the total symptom severity score on the CAPS-5. The CAPS-5 has good internal consistency, inter-rater reliability, test-retest reliability and convergent validity in measuring PTSD symptom severity, and is regarded as the gold-standard for measuring PTSD symptoms in research settings. The CAPS-5 will be used to query the presence of PTSD symptoms across the two weeks prior to each CAPS-5 assessment. We will also compare between-group differences in remission rates of PTSD, as determined by the CAPS-5.

Timepoint [1]

At baseline and at week 12 of the study period

Secondary outcome [1]

Hamilton Anxiety Rating Scale (HAM-A)

Assessment method [1]

Timepoint [1]

At baseline, at week 12 and at week 16 of the study period

Secondary outcome [2]

Generalized Anxiety Disorder-7 (GAD-7)

Assessment method [2]

One of the Secondary Outcome Measures will be the between-group difference in the change from baseline to week 12, and baseline to week 16 (while including all available time-points including the off-treatment period) in measures of anxiety symptoms on the GAD-7. Additional comparisons for between-group differences from week 12 to week 16 will also be performed. The Generalized Anxiety Disorder-7 is a 7-item scale with each item scores on a scale of 0 ("not at all") to 3 ("nearly every day") based on symptom presentation in the past two weeks.

Timepoint [2]

At baseline, at week 12 and at week 16 of the study period

Secondary outcome [3]

Generalized Anxiety Disorder-7 (GAD-7)

Assessment method [3]

One of the Secondary Outcome Measures will be the longitudinal trajectory analysis of anxiety symptoms on the GAD-7, measured at baseline, week 4, week 8 and week 12 of treatment. The Generalized Anxiety Disorder-7 is a 7-item scale with each item scores on a scale of 0 ("not at all") to 3 ("nearly every day") based on symptom presentation in the past two weeks.

Timepoint [3]

At baseline, week 4, week 8 and week 12 of the study period

Secondary outcome [4]

Beck Depression Inventory-II (BDI-II)

Assessment method [4]

One of the Secondary Outcome Measures will be the between-group difference in the change from baseline to week 12, and baseline to week 16 (while including all available time-points including the off-treatment period) in measures of depressive symptoms on the BDI-II. Additional comparisons for between-group differences from week 12 to week 16 will also be performed. The BDI-II comprises of 21 questions rated on 4-point scales of severity (0-3), with a total score that reflects the level or degree of depression. The BDI-II has high internal consistency.

Timepoint [4]

At baseline, at week 12 and at week 16 of the study period

Secondary outcome [5]

Patient Health Questionnaire-9 (PHQ-9)

Assessment method [5]

One of the Secondary Outcome Measures will be the between-group difference in the change from baseline to week 12, and baseline to week 16 (while including all available time-points including the off-treatment period) in measures of depressive symptoms on the PHQ-9. Additional comparisons for between-group differences from week 12 to week 16 will also be performed. The Patient Health Questionnaire-9 is a screening measure of depressive symptoms. The PHQ-9 asks participants to rate each of the 9 DSM-IV criteria for major depressive disorder from 0 ("not at all") to 3 ("nearly every day").

Timepoint [5]

At baseline, at week 12 and at week 16 of the study period

Secondary outcome [6]

Patient Health Questionnaire-9 (PHQ-9)

Assessment method [6]

One of the Secondary Outcome Measures will be the longitudinal trajectory analysis of depressive symptoms on the PHQ-9, measured at baseline, week 4, week 8 and week 12 of treatment. The Patient Health Questionnaire-9 is a screening measure of depressive symptoms. The PHQ-9 asks participants to rate each of the 9 DSM-IV criteria for major depressive disorder from 0 ("not at all") to 3 ("nearly every day").

Timepoint [6]

At baseline, week 4, week 8 and week 12 of the study period

Secondary outcome [7]

Patient Health Questionnaire-15 (PHQ-15)

Assessment method [7]

One of the Secondary Outcome Measures will be the between-group difference in the change from baseline to week 12, and baseline to week 16 (while including all available time-points including the off-treatment period) in measures of somatic symptoms on the PHQ-15. Additional comparisons for between-group differences from week 12 to week 16 will also be performed. The Patient Health Questionnaire-15 is a Patient Health Questionnaire module designed to assess the presence of somatic symptoms. The PHQ-15 has good internal consistency and test-retest reliability.

Timepoint [7]

At baseline, at week 12 and at week 16 of the study period

Secondary outcome [8]

Patient Health Questionnaire-15 (PHQ-15)

Assessment method [8]

One of the Secondary Outcome Measures will be the longitudinal trajectory analysis of somatic symptoms on the PHQ-15, measured at baseline, week 4, week 8 and week 12 of treatment. The Patient Health Questionnaire-15 is a Patient Health Questionnaire module designed to assess the presence of somatic symptoms. The PHQ-15 has good internal consistency and test-retest reliability.

Timepoint [8]

At baseline, week 4, week 8 and week 12 of the study period

Secondary outcome [9]

Pittsburgh Sleep Quality Index, with Addendum for PTSD (PSQI & PSQI-A)

Assessment method [9]

One of the Secondary Outcome Measures will be the between-group difference in the change from baseline to week 12, and baseline to week 16 (while including all available time-points including the off-treatment period) in measures of sleep quality on the PSQI \& PSQI-A. Additional comparisons for between-group differences from week 12 to week 16 will also be performed. The Pittsburgh Sleep Quality Index is designed to measure overall sleep quality during the previous month in a clinical population. The PSQI comprises 19 questions across 7 domains or "component" scores, each weighted equally on a 0-3 scale. The PSQI will include the PTSD Addendum (PSQI-A), which are 10 additional questions designed to assess the frequency of disruptive nocturnal behaviours.

Timepoint [9]

At baseline, at week 12 and at week 16 of the study period

Secondary outcome [10]

Pittsburgh Sleep Quality Index, with Addendum for PTSD (PSQI & PSQI-A)

Assessment method [10]

One of the Secondary Outcome Measures will be the longitudinal trajectory analysis of sleep quality on the PSQI \& PSQI-A, measured at baseline, week 4, week 8 and week 12 of treatment. The Pittsburgh Sleep Quality Index is designed to measure overall sleep quality during the previous month in a clinical population. The PSQI comprises 19 questions across 7 domains or "component" scores, each weighted equally on a 0-3 scale. The PSQI will include the PTSD Addendum (PSQI-A), which are 10 additional questions designed to assess the frequency of disruptive nocturnal behaviours.

Timepoint [10]

At baseline, week 4, week 8 and week 12 of the study period

Secondary outcome [11]

Alcohol Use Disorders Identification Test (AUDIT)

Assessment method [11]

One of the Secondary Outcome Measures will be the between-group difference in the change from baseline to week 12, and baseline to week 16 (while including all available time-points including the off-treatment period) in measures of problematic alcohol use on the AUDIT. Additional comparisons for between-group differences from week 12 to week 16 will also be performed. The Alcohol Use Disorders Identification Test is a 10-item questionnaire developed through a 6-country World Health Organization collaborative project, as a screening tool for harmful alcohol consumption. The AUDIT spans the domains of alcohol consumption, drinking behaviour, and alcohol-related problems that may have occurred in the past year, as well as lifetime exposure.

Timepoint [11]

At baseline, at week 12 and at week 16 of the study period

Secondary outcome [12]

Alcohol Use Disorders Identification Test (AUDIT)

Assessment method [12]

One of the Secondary Outcome Measures will be the longitudinal trajectory analysis of problematic alcohol use on the AUDIT, measured at baseline, week 4, week 8 and week 12 of treatment. The Alcohol Use Disorders Identification Test is a 10-item questionnaire developed through a 6-country World Health Organization collaborative project, as a screening tool for harmful alcohol consumption. The AUDIT spans the domains of alcohol consumption, drinking behaviour, and alcohol-related problems that may have occurred in the past year, as well as lifetime exposure.

Timepoint [12]

At baseline, week 4, week 8 and week 12 of the study period

Secondary outcome [13]

World Health Organization (WHO) Disability Assessment Schedule (WHODAS 2.0)

Assessment method [13]

One of the Secondary Outcome Measures will be the between-group difference in the change from baseline to week 12, and baseline to week 16 (while including all available time-points including the off-treatment period) in measures of functional disability on the WHODAS 2.0. Additional comparisons for between-group differences from week 12 to week 16 will also be performed. The 12-item self-report version of the World Health Organization (WHO) Disability Assessment Schedule is a measure of functioning and disability across six major life domains due to health conditions. The WHODAS has high internal consistency and test-retest reliability.

Timepoint [13]

At baseline, at week 12 and at week 16 of the study period

Secondary outcome [14]

General Well Being Schedule (GWBS)

Assessment method [14]

One of the Secondary Outcome Measures will be the between-group difference in the change from baseline to week 12, and baseline to week 16 (while including all available time-points including the off-treatment period) in measures of general well-being on the GWBS. Additional comparisons for between-group differences from week 12 to week 16 will also be performed. The General Well Being Schedule is an 18-item measure of subjective psychological well-being and distress. The GWBS has good test-retest reliability, as well as internal consistency for both sexes.

Timepoint [14]

At baseline, at week 12 and at week 16 of the study period

Secondary outcome [15]

Assessment of Quality of Life-6D (AQoL-6D)

Assessment method [15]

One of the Secondary Outcome Measures will be the between-group difference in the change from baseline to week 12, and baseline to week 16 (while including all available time-points including the off-treatment period) in measures of quality of life on the AQoL-6D. Additional comparisons for between-group differences from week 12 to week 16 will also be performed. The Assessment of Quality of Life-6D scale is a 20-item, 6-dimensional measure with each item containing between 4 and 6 response levels. The AQoL-6D assesses the following 6 domains of quality of life: Independent Living, Relationships, Mental Health, Coping, Pain and Senses.

Timepoint [15]

At baseline, at week 12 and at week 16 of the study period

Secondary outcome [16]

PTSD Checklist for DSM-5 (PCL-5)

Assessment method [16]

One of the Secondary Outcome Measures will be the will be the between-group difference in the change from intake to week 12, and intake to week 16 (while including all available time-points including the off-treatment period) in measures of quality of life on the PCL-5. Additional comparisons for between-group differences from week 12 to week 16 will also be performed. The PTSD Checklist for DSM-5 is a 20-item self-report measure that assesses the presence and intensity of each of the 20 DSM-5 PTSD symptoms. The PCL-5 has been shown to have strong reliability and validity. A score of = 33 suggests PTSD.

Timepoint [16]

At intake, at week 12 and at week 16 of the study period

Secondary outcome [17]

PTSD Checklist for DSM-5 (PCL-5)

Assessment method [17]

One of the Secondary Outcome Measures will be the longitudinal trajectory analysis of PTSD symptom severity on the PCL-5, measured at intake, and at week 2, week 4, week 6, week 8 and week 12 of treatment. The PTSD Checklist for DSM-5 is a 20-item self-report measure that assesses the presence and intensity of each of the 20 DSM-5 PTSD symptoms. The PCL-5 has been shown to have strong reliability and validity. A score of = 33 suggests PTSD.

Timepoint [17]

At intake, week 2, week 4, week 6, week 8 and week 12 of the study period

Secondary outcome [18]

Patient Global Impression of Change Scale (PGIC)

Assessment method [18]

One of the Secondary Outcome Measures will be the longitudinal trajectory analysis of patient global impression of change on the PGIC, measured at week 2, week 4, week 6, week 8 and week 12 of treatment. The Patient Global Impression of Change Scale asks participants to rate the change (if any) that they have experienced since starting treatment, on a scale of 1 ("No change") to 7 ("A great deal better and a considerable improvement that has made all the difference").

Timepoint [18]

Week 2, week 4, week 6, week 8 and week 12 of the study period

Secondary outcome [19]

Actigraphy watches

Assessment method [19]

One of the Secondary Outcome Measures will be the longitudinal trajectory analysis of sleep, actigraphy, and physiological measures (including mean heart rate, mean heart rate variability, mean blood pressure), measured continuously throughout the study period (baseline to week 16).

Timepoint [19]

Continously from baseline until week 16 of the study period

Eligibility

Key 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.

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key 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).

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Parallel

Other design features

Phase

Phase 3

Type of endpoint/s

Statistical methods / analysis

Recruitment

Recruitment status

Recruiting

Data analysis

Reason for early stopping/withdrawal

Other reasons

Date of first participant enrolment

Anticipated

Actual

26/08/2024

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

31/03/2027

Actual

Sample size

Target

224

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

University of Melbourne - Carlton

Recruitment hospital [2]

Deakin University - Geelong

Recruitment hospital [3]

Austin Health - Heidelberg

Recruitment hospital [4]

Ramsay Clinic Albert Road - Melbourne

Recruitment postcode(s) [1]

5053 - Carlton

Recruitment postcode(s) [2]

3220 - Geelong

Recruitment postcode(s) [3]

3084 - Heidelberg

Recruitment postcode(s) [4]

3004 - Melbourne

Funding & Sponsors

Primary sponsor type

Other

Name

Deakin University

Country

Other collaborator category [1]

Other

Name [1]

University of Melbourne

Country [1]

Other collaborator category [2]

Other

Name [2]

Ramsay Clinic Albert Road

Country [2]

Ethics approval

Ethics application status

Summary

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.

Trial website

https://clinicaltrials.gov/study/NCT06412757

Public notes

Contacts

Principal investigator

Name

Michael Berk, PhD

Address

Deakin University

Country

Phone

Contact person for public queries

Name

Greg Roebuck, MD

Address

Country

Phone

+61 3 9035 4749

greg.roebuck@unimelb.edu.au

Contact person for scientific queries

Data sharing statement

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT06412757

Trial Review

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06412757