SerTRaline for AnxieTy in adults with a diagnosis of Autism (STRATA) A randomised controlled trial.
A multicentre double-blind placebo-controlled randomised trial of SerTRaline for AnxieTy in adults with Autism (STRATA)-Australian component.
The University of Western Australia (UWA)
75 participants
Feb 9, 2022
Interventional
Conditions
Summary
Anxiety is common in autistic adults and can be more disabling than the core features of autism. Medications for anxiety are often prescribed for autistic adults but their effectiveness or side effects in this population are not well known. Research findings in non-autistic populations may not apply to autistic adults. This study aims to find out whether the drug sertraline is an effective treatment for anxiety in adults with a diagnosis of autism. We will compare the use of sertraline in autistic adults with placebo, a non-active identical capsule. We are interested to see whether the treatment improves symptoms of anxiety, enhances quality of life, and is effective in the longer term. We are also interested in understanding side effects of the treatment. We will run this trial in five geographical regions in England and Western Australia. We aim to include 75 people in Australia (total study population will be 306 internationally) who will be allocated at random to receive either encapsulated sertraline or identical inactive placebo, which they will be asked to take for up to 12 months. They will be asked to complete questionnaires about themselves, their anxiety and mental health, use of services, and any adverse effects they may experience at several time points. The results will help understand whether sertraline is an acceptable treatment and whether it is better or not than placebo in the treatment of anxiety in autistic adults.
Eligibility
Inclusion Criteria5
- Adults aged greater than or equal to 18 years.
- A diagnosis of autism made by a specialist including those with a co-occurring mild intellectual disability [autism diagnostic terms may include autism/autistic spectrum disorder or other variations, Asperger syndrome/disorder or pervasive developmental disorder].
- Anxiety as measured by GAD-7 score greater than or equal to 10 at screening
- Carer Burden Nested Sub Study
- For the purpose of this carer burden sub-study, it is up to the STRATA (main trial) participant to define who their carer is; where feasible, it would be one carer who knows them well and is likely to continue caring for them over the 52-week trial period. All named carers will be approached and invited to participate in the carer sub study.
Exclusion Criteria16
- Prescribed a serotonergic antidepressant/anxiolytic at antidepressant doses in preceding 8 weeks- these include SSRI and non-SSRI antidepressants including tricyclic antidepressants. Potential participants who are prescribed low (i.e. non-antidepressant) doses of these medications for other indications (e.g. neuropathic pain); or those who had no such medication for the majority of the preceding 8 weeks (e.g. tried for a few days before stopping) may be considered eligible where the PI confirms this is consistent with usual clinical practice. Individuals prescribed these medications wishing to participate could do so after a washout period of 8 weeks.
- Prescribed an irreversible monoamine oxidase inhibitor or Pimozide in the preceding 8 weeks.
- Diagnosis of moderate-severe intellectual disability (ID). People who have up to mild ID will be eligible. For the purpose of this study, a person with known intellectual disability will be considered as having a mild ID if they are able to provide written informed consent, and the ability to understand and answer the study questionnaires with the help of reasonable adjustments, if necessary.
- Inability to provide informed consent and complete study assessments/questionnaires.
- Current valid diagnosis of bipolar disorder, manic or hypomanic episodes, or psychosis. Individuals with historical diagnoses where there is clinical consensus or strong suspicion that these diagnoses are no longer valid (e.g. presentations historically labelled as mania/psychosis now considered to be explained by autism) may be considered eligible based on PI discretion.
- Currently uncontrolled epilepsy.
- Known current alcohol or drug use problem (i.e. if recorded in patient/medical notes and the GP/PI considers it unsafe to co-prescribe sertraline).
- Known allergies to sertraline or placebo/excipients.
- Currently enrolled in another medication RCT.
- Women who are pregnant, are planning pregnancy, or breastfeeding.
- History of severe liver impairment.
- Bleeding disorders such as such as haemophilia, Christmas disease and von Willebrands disease, as well as those with past medical history of bleeding gastric or duodenal ulcers or other significant bleeding disorders.
- History of long QT syndrome or Torsade de Pointes.
- Swallowing difficulties or inability to take medication in capsule form.
- Currently using St. John’s Wort.
- Carer Burden Nested Sub Study
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Interventions
The research project is a two parallel group multi-centre pragmatic randomised controlled trial (RCT) of sertraline versus placebo for reducing anxiety in adults with a diagnosis of autism. The active investigational medicinal products are over-encapsulated 25mg or 50mg Sertraline tablets with a back fill of microcrystalline cellulose powder. All participants will receive a daily oral dose of 25mg sertraline or placebo for 2 weeks followed by 2x25mg for 4 weeks. Following this initiation period, the medication will be dispensed in 50mg capsules and depending upon tolerability, the dose will be flexibly increased by 50mg every 4-weeks to reach the optimal dose. The dose will only be increased if the participant is tolerating it and agrees to try an increased dose, and the prescribing clinician is satisfied that it is appropriate to do so based on the participant’s responses to the safety check questionnaire and discussion with the study research staff. The dose may go up to a maximum of 200mg by week 14, although it is anticipated that for many patients the optimal dose may be lower than this amount (e.g. 50mg, 100mg or 150mg) and reached before this time. Participants will take this optimal dose for up to 52-weeks post-randomisation, which will be the maximum planned time unless there are indications to stop earlier. Participants can choose to withdraw for any reason at any time during their involvement in the trial. Participants can withdraw from: (a) taking study medication, although participants who have taken at least one study medication capsule will be informed that they should take the treatment regimen for at least 16-weeks (i.e. until the primary outcome timepoint) before deciding if the treatment works or not; and (b) providing data to the trial, at any time for any reason without affecting their usual care. The PI can also decide to withdraw participants based on clinical opinion at any time during the trial; a likely scenario might be withdrawing them from taking the study medication. This may be due to safety concerns, severe adverse effects, development of mania or psychosis, or loss of contact such that sending further medication is not deemed safe. Brief contact (safety checks): 1 to 2-, 4-, 8-, 12-, and 36-weeks post-randomisation At 1 to 2-, 4-, 8-, 12- and 36-weeks post-randomisation*, the local research (recruitment) team will contact the participant to conduct a brief safety check to assess safety (adverse effects), medication dose titration and adherence (including tablet counting, and return of unused medication), and anxiety and depressive symptoms (including suicidality). This assessment will be carried out via questionnaire and discussion to adequately inform dose titration. The researcher will convey this assessment to the local PI (“prescriber”, or authorised delegate) for them to review and make the decision regarding further prescription (continue on same dose, increase or decrease). If required, the PI/clinician can arrange to speak with/or arrange to see the participant directly or request further information to enable their decision. The decision to prescribe and amend dosage shall stay with the PI/clinician and not the RA who is responsible for conveying the relevant information to the PI/clinician. * The initial safety check at 1 to 2 weeks should be at least 1-week, but no later than 2-weeks, post-randomisation. This flexibility is due to potential delay time between being randomised and starting the medication (eg. Picking up or postage delays in medication collection). We anticipate the need for flexibility of +/- 1-week given the pragmatic nature of this trial for the safety checks at 4-, 8-, 12- and 36-weeks post-randomisation. It is important to note, however, that medication dosage must be discussed with research staff rather than via online questionnaire, only. Where safety is a concern, participants will be encouraged to seek input from their clinician/GP to help with clinical management. Follow up assessments: 16-, 24- and 52-weeks post-randomisation Participants will be asked to complete a STRATA Follow Up Questionnaire 16-, 24- and 52- weeks post-randomisation, as well as the assessments completed at the brief safety check timepoints. Carer Burden Nested Sub Study A nominated carer of all recruited participants will be invited to participate in a carer sub study, and recruited in parallel to explorer carer burden. It is up to the STRATA participant to define who their carer is; where feasible, it would be one carer who knows them well and is likely to continue caring for them over the 52-week trial period. The carer will be approached only with the agreement of the participant and consented separately. The participant is still able to participate in the trial if carers do not wish to participate, or if there is no carer. Similarly, the carer can continue involvement if the participant withdraws from the main trial. Carers will be asked to complete a STRATA Carer Burden Questionnaire at Baseline, 16- and 52-weeks post-randomisation of the STRATA (main trial) participant.
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ACTRN12621000801819