Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT04908969 |
| Other study ID # |
2020-00479 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
April 15, 2021 |
| Est. completion date |
August 23, 2023 |
Study information
| Verified date |
October 2022 |
| Source |
Karolinska Institutet |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Tic disorders, including Tourette's Disorder (TD) and Chronic Motor or Vocal Tic Disorder
(CTD), are neurodevelopmental motor disorders characterised by motor and/or vocal tics.
TD/CTD are impairing conditions with onset during childhood that often persist into
adulthood. Behaviour therapy (BT) is an effective treatment for TD/CTD and is recommended as
a first-line intervention in both in children and in adults. However, most adults with TD/CTD
do not have access to BT due to a lack of trained professionals and geographical barriers.
The objective of the study is to adapt and extend existing face-to-face BT treatment
protocols for adults with TD/CTD to an internet-delivered format and evaluate its feasibility
and preliminary efficacy. A total of 30 adult TD/CTD adult patients deemed eligible for the
study through the recruitment process involving both psychologist and physician assessment
will be enrolled in the project. The 8-modues treatment program, mainly based on exposure
with response prevention with addition of other techniques will be made available for the
participants in a secure treatment platform. The participants will keep in touch with a
therapist using two-ways written communication in the same platform. The therapist's role
will be to introduce the treatment and its modules, give feedback on the homework assignments
and open the new modules as well as monitor the participants psychiatric symptoms and
activity in the plattform. The measures will include tic severity secifically and disease
severity in general, anxiety and depression symptoms, quality of life, treatment credibility
and therapeutic alliance. The measures will be administrated at baseline, min- and
post-tretment, as well at 3 and 12 months follow-up. Upon completion, this project will be
the first crucial step towards the implementation of internet-delivered behaviour therapy
(I-BT) for adults with TD/CTD in regular health care.
Description:
Background
TS (Tourette Syndrome) is characterized by multiple motor tics and one or more vocal tics
that have persisted for at least one year since initial onset, whereas in Chronic Motor or
Vocal Tic Disorder (CTD) either motor or vocal tics are present, but not both, during at
least one year (1). It is a childhood-onset disorder that affects more boys than girls (4:1
ratio) with a prevalence of about 1% in children (2), of which a substantial proportion
continue to experience impairing tics into adulthood (3,4,5). TS/CTD are associated with
reduced quality of life (6), lower educational attainment (7), and increased risk for
cardiovascular and metabolic disorders (8). Notably, individuals with TD/CTD have a four-fold
increased risk of death by suicide and the risk is highest for those whose tics persist into
adulthood (9). Thus, effective interventions and appropriate follow-up are crucial to prevent
undesirable health consequences and societal costs.
Evidence-based treatments for Tourette's Disorder and Chronic Tic Disorder
Historically, the most common treatment for TS/CTD has been pharmacotherapy, specifically
antipsychotics. However, pharmacological treatments are modestly efficacious in reducing tics
and often have undesirable side effects such as tiredness or long-term metabolic problems
(10). Non-drug treatments for TS/CTD are therefore attractive alternatives. Behavioural
treatments acknowledge that tics have a biological origin but that their expression is
influenced by contextual variables: feelings, sensations, situations or other triggers that
occur before tics. CBT focuses on modifying environmental factors that influence tic severity
and teaches patients specific skills they can use to better manage their tics (11). CBT for
tics generally includes two main elements. First, the patient learns how to detect their tics
on a daily basis. Secondly, the patient learns how to resist the tics. CBT for TS/CTD has
shown to be effective against waiting list (12) and against an active control group (13-16),
with sustained results up to one year after treatment completion (17, 18). Expert guidelines
in Europe and elsewhere recommend CBT as the first-line treatment for TS/CTD (17, 18).
Preferred treatments are not available
Surveys among young people with tics and their parents indicate that cognitive behavioural
therapy is their preferred treatment option (19). However, this intervention is not widely
available for TS/CTD (20). Thus, despite patient preferences and the problematic side effects
of drugs, the vast majority of TS/CTD patients in Sweden receive only medication to treat
their tics. Members of our team conducted an epidemiological study looking at all patients
diagnosed with TS or CTD (n=6,979) in Sweden and found that over 75% of them received at
least one drug, and over 70% were on at least two types of drugs. Moreover, prescription of
anxiolytics, hypnotics/sedatives, ADHD drugs, and atypical antipsychotics increased over the
8-year study period (21).
In sum, expert therapists trained to treat TS/CTD with CBT in Sweden are lacking. Even in
Stockholm County, it is our clinical experience that many adult patients with TS/CTD have
trouble finding the appropriate expertise when seeking treatment in primary care, neurology,
or psychiatry.
A remote cognitive behavioural intervention for adults with Tourette Syndrome
There has been an increase in uptake of information and communication technology within
health care in recent years. One such innovation is to provide the treatment online instead
of face-to-face. In internet-delivered psychological treatments, the treatment is provided in
the form of self-help texts, homework assignments, and worksheets for the patient to fill in
online. An identified therapist provides support and guidance throughout treatment via a
built-in messaging system. Internet-delivered treatments is a burgeoning research field where
Sweden is at the forefront of international development (22). Internet-delivered treatments
have been developed and evaluated by our research team for many psychiatric conditions,
including disorders related to TS/CTD, such as obsessive-compulsive disorder (OCD) and body
dysmorphic disorder (BDD) (23-26). Internet-delivered treatments have consistently shown
comparable effects to traditional face-to-face therapies (27) while requiring less therapist
time per patient and being delivered remotely, thus being cost-effective for health care and
accessible to patients (28). Preliminary results suggest that videoconferencing (29) and
I-CBT (30) are feasible options for children with TS/CTD, but there are no such treatments
available to adults with TS/CTD.
Research questions
There is an urgent need to disseminate evidence-based treatments for adults with TS and CTD.
Internet-delivered cognitive behavioural therapy (ICBT) for TD/CTD will be a feasible,
acceptable, and safe method to deliver evidence-based treatment for adults with TS/CTD. We
also hypothesize that I-CBT will show preliminary efficacy in reducing tic severity in this
population.
Methods
Study design
The aim of the project will be to carry out a pilot trial to evaluate the feasibility,
acceptability, safety, and efficacy of the internet-delivered treatment for TS/CTD. We also
aim to further refine the treatment based on feedback from participants and therapists
involved in the trial. Furthermore, information obtained from this feasibility trial will
allow us to investigate key design and methodological issues to inform the protocol of a
subsequent full scale randomised controlled trial. Specifically, the generated within
participant data will be critical to perform a power analysis for a more definitive trial
(see power analysis section).
The study design and outcomes will be registered online at ClinicalTrials.gov prior to
inclusion of the first participant. We will also upload the scripts used for statistical
analyses to an online repository (such as the Open Science Framework or Github).
Outcome measures
Feasibility measures: Feasibility will be assessed according to the RE-AIM framework (reach,
effectiveness, adoption, implementation, maintenance) (33). Reach will be measured by looking
at the percentage eligible/excluded, reasons for refusal or exclusion.
Efficacy measures: Unless specified otherwise, all outcome measures will be administered at
baseline, post-treatment (primary end-point), 3-month follow-up, 6-month follow-up, and
12-month follow-up. Primary outcome measure: YGTSS TTSS. Secondary disorder-specific
outcomes: YGTSS Impairment scale, Adult Tic Questionnaire (weekly). Functioning and quality
of life measures: The Clinical Global Impression - Severity (CGI-S) and Clinical Global
Impression - Improvement (CGI-I) Scales will be used to assess overall clinical severity and
consequent treatment response (scores of "very much improved" (1) or "much improved" (2) will
define treatment response according to previous trials in tic disorders (14, 16). In
addition, Global Assessment of Functioning (GAF), Sheehan Disability Scale (SDS), EuroQol
5-dimensions (EQ-5D), Gilles de la Tourette Syndrome Quality of Life Scale (QTS-QoL) will be
used to evaluate functioning and quality of life. Depressive symptoms: MADRS-S will be
administered weekly to follow depressive symptoms during treatment.
Procedure
Patients with TS/CTD will be recruited through our clinic (OCD-programmet) as well as through
self-referral. Information about the study will be communicated to patient associations (such
as OCD-förbundet and Attention), health centers, psychiatric outpatient clinics, internal
referral systems (remissportal) as well as advertised in the media and in social media.
Self-referral will be made available through an internet website constructed for the study.
The website will contain information about the study, the research group, and contact
information. Screening: Self-referred participants will go through a telephone screening
containing information about the study and an assessment of inclusion and exclusion criteria.
If the presumptive participant is deemed fit for inclusion, they will be scheduled for a
visit with a study clinician. Patients that are recruited through internal referral systems
will not go through the screening procedure but will be scheduled for a visit with a study
clinician. Assessment: Potential participants will be assessed face to face at our clinic in
Stockholm for eligibility to participate (see inclusion and exclusion criteria above) by a
study clinician. The assessment includes an assessment if the participant fulfil the
diagnostic criteria of a TS/CTD diagnosis based on a review of medical history and the DSM-5
diagnostic criteria. The YGTSS will be administered to establish symptom severity. A
semi-structured clinical psychiatric interview (the Mini-International Neuropsychiatric
Interview; MINI), as well as the SCID-1 section for OCD and related disorders (OCD, BDD,
tricho- and dermatillomania, hoarding disorder) will be administered in order to assess
psychiatric comorbidities. This routine corresponds to the regular diagnostic assessment at
the clinic. Patients suitable for study participation will be given information about the
study and asked to sign a form giving their informed consent to participate in the study.
Participants will initiate treatment within a week and begin by filling in self-report
measures on the internet (listed under Efficacy measures, above). Patients who decline
participation in the study will be offered regular treatment at the clinic or, depending on
the individual's needs, be referred to other clinical services.
Treatment
Interventions: As described above, the treatment protocol will be adapted from existing
validated protocols for face-to-face treatment and remote delivery (12-16, 30).
The treatment will be provided through a secure internet platform designed for
internet-administered treatments (BASS-4). The platform has been studied extensively and is
currently a part of the Swedish public health care services. In the treatment, the patient
works through modules of self-help material, each ending in a short quiz with questions about
the material. The treatment is supported by a therapist through text-based communication via
the platform as well as occasional phone calls when needed. The central component in the
treatment is exposure and response prevention (ERP). In ERP, the patient exposes her/himself
to situations that trigger premonitory urges (a type of bodily sensation that precede the
tic) while practicing to resist the tic. By doing this systematically and repeatedly, the
patient gradually learns how to tolerate the premonitory urges and increase the ability to
control and resist doing tics. Beyond ERP the treatment consists of other components such as
applied relaxation, counter-movements and interventions to decrease stressors in the
patient's everyday life.
Therapist training, supervision, and quality control
Therapists will be licensed clinical psychologists, psychologists in training or fifth-year
clinical psychology students under supervision. As all communication with the patients is
stored in the platform, continuous monitoring and supervision is possible and will be
provided by the study coordinator to ensure adherence. All assessors will be trained on the
use of the primary outcome measure, the YGTSS (32) using case examples, and inter-rater
reliability scores will be obtained. The study is approves by the Ethical Review Authority.
The trial will be conducted in accordance with Good Clinical Practice (GCP) and results will
be reported in accordance with the CONSORT statement for non-pharmacological trials.
Statistical analysis
Power calculation
Given a standardized (Cohen's d) within-group effect size of 0.5 to 1 in previous research of
remote therapy for TS/CTD (30), we aim to recruit 30 participants in order to be able to
detect an effect size of d = 0.7, allowing for a 20% dropout (90% power, alpha 0.05). The
primary outcome analysis will also inform the power analyses of a future large-scale
randomised controlled trial via the variance of intercept, fixed effects, random effects, and
residual variance for the YGTSS in the mixed effects model. These estimates will help us
select the appropriate number of participants to make the results from the randomised
controlled trial informative and useful.
Outcome analyses
The primary and secondary outcome measures will be evaluated using mixed-effects linear
regression models with a fixed effect of time, as well as random intercept and random slope
specifications for each individual. Within-group effect sizes will be calculated using
Cohen's d by dividing the mean change between the time-points by the pooled standard
deviation of that measure at pre-treatment. To maximize replicability and transparency, all
statistical code will be published in public repositories.
