In a randomized single-blinded trial we compare two treatments for GTS and CTD patients. The primary aim of this study is to compare the efficacy of the D2-blocking agent risperidone with ERP-therapy in tic reduction. Dropout rates and side effects…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
neuropsychiatrische aandoening (syndroom van Gilles de la Tourette en aanverwante chronische ticstoornissen)
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary outcome measure will be tic severity according to the Yale Global Tic
Severity Scale (YGTSS, Leckman et al, 1989) directly post treatment ( after 12
weeks), as measured by trained experts, blinded for the allocated treatment.
The YGTSS is a widely used clinical rating scale that provides information on
tic severity for motor and vocal tics in five dimensions: number, frequency,
intensity, complexity, and interference. A rating of impairment is added to
provide a total Tic severity score that ranges from 0 (no tics) to 55 (severe
tics).
The YGTSS has demonstrated satisfactory convergent and discriminant validity
and interrater reliability.
Secondary outcome
Secundary outcome measures include ticfrequency at home and at the institute
after 12 weeks, and tic severity and frequency at home and at the institute
after 6 and 12 months (follow-up). General assessment of functioning and
quality of life, cost-effectiveness, severity of premonitory sensations, side
effects and severity of comorbidity will be measured as well, as are effects
during half way of treatment (after 6 weeks). Prognostic factors for response
on the two treatments will be analysed with the use of multivariate analysis.
Ticfrequency at home will be measured by daily registrations by a parent/
partner of the patient. They count the number of tics in a 15 minute interval
during a fixed time/ activity. Tic frequency at the institute will be measured
by counting tics of videotaped YGTSS measures. Standardized videotaped tic
counts of at least 5-minute samples have previously been found to provide
reliable and stable measures of tic frequency and are sufficiently correlated
with YGTSS ratings (Chapell et al., 2004).
Quality of life is measured by the Gilles de la Tourette Syndrome*Quality of
Life Scale(GTS-QOL, Cavanna et al, 2008). The GTS-QOL is a
27-item, patient-reported scale which measures GTS-specific health related
quality of life on 4 subscales. The GTS-QOL
demonstrated high reliability and test-retest reliability, and supported
validity. The economic evaluation will use a societal perspective: we will
document mental and general health care utilization (direct medical costs),
travel to and from health care providers (non-medical costs) and productivity
loss generated by absence from paid work (indirect costs).TIC-P (Trimbos/iMTA
questionnaire for costs associated with psychiatric illness, Hakkaart-van
Roijen, 2002) will be administered. The TiC-P is a generally applied tool to
estimate health care utilisation and production losses by self-report from
recipients (patients with mental health problems) in the Dutch health care
setting. It is often used to determine costs in economic evaluations.
Premonitory urge severity is measured using the Premonitory Urge for Tics Scale
(PUTS, Woods et al, 2005). The PUTS is a brief self-report scale designed to
measure tic-related premonitory urges. Side effects are measured by the UKU
Side Effects Rating Scale (Lingjaerde et al., 1987) and the Extrapyramidal
Symptom Rating Scale (ESR, Chouinard et al, 1980) for measuring parkinsonian
and dyskinetic symptoms.
In case of comorbid OCD, the Yale Brown Obsessive Compulsive Scale (Y-BOCS,
Goodman et al., 1989) or Children*s Yale Brown Obsessive Compulsive Scale
(CY-BOCS, Scahill et al, 1997) is administered. If ADHD is present, the
severity is measured in adults with the Conners' Adult ADHD Rating Scales
(CAARS, Conners et al, 1999), and in children with the Conners' rating
scales-revised (CRS-R, Conners, 1997). Autism is measured with the Adults
Social Behavior Questionnaire (VIS-V, van den Bosch et al, 2002) for adults
and the Children*s Social Behavior Questionnaire (VISK, Luteijn et al, 2002)
for children.
Background summary
Gilles de la Tourette syndrome (GTS) and chronic tic disorders (CTD) are
neuropsychiatric disorders, starting below age 18, and characterized by tics.
Tics may have severe impact on daily and social life, may interfere with work,
be painful due to the overstraining of muscles or joints, and thus become a
severe handicap for patients. Effective treatment of tics is essential to
enlarge the quality of life. To date, D2-blocking agents (antipsychotic drugs)
are regarded as treatment of first choice, but these drugs are not well
tolerated and stopped by up to 70 percent of the patients within the first
year. Also, many patients are reluctant to take antipsychotics. Several
randomised controlled studies showed behaviour therapy as an effective
treatment method for tics. One of these methods is exposure and response
prevention (ERP). In ERP, patients are exposed to the unpleasant sensory
sensation, which often precedes the actual tic. By withholding the tic,
patients learn to adapt to the sensory sensations, resulting in reduction of
tic frequency. We are not aware of any comparative study between D2-blocking
agents and ERP in patients with GTS or CTD. The primary aim of the present
study is to compare the efficacy of the D2-blocking agent risperidone with ERP
in tic reduction in patients with GTS or CTD. We expect ERP to be more
effective than medication based on higher effect sizes in earlier studies,
fewer side effects, lower dropout rates and better long-term effects.
Secondary, we aim at identifying prognostic factors with regard to therapy
response. 80 GTS or CTD patients will be randomized to receive either
risperidone (2-6 mg. per day) or ERP during 12 weeks. After a baseline of 2
weeks and treatment of 12 weeks, treatment response is measured. The primary
outcome measure will be tic severity as measured by the Yale Global Tic
Severity Scale (YGTSS, Leckman et al., 1989) directly post-treatment. The YGTSS
is scored by trained assessors, blinded for the allocated treatment. Secondary
outcome measures include video-taped tic counts, cost-effectiveness, measures
of quality of life and general functioning post-treatment. Furthermore, long
term effects will be measured by follow-up (week 24 and 52).
Study objective
In a randomized single-blinded trial we compare two treatments for GTS and CTD
patients. The primary aim of this study is to compare the efficacy of the
D2-blocking agent risperidone with ERP-therapy in tic reduction. Dropout rates
and side effects are taken into consideration. Secondary, we want to measure
cost-effectiveness and identify prognostic factors with regard to treatment
response. At last, long-term effectiveness will be measured by follow-up.
Study design
This study is a randomized, single blinded effectiveness study, in which a
comparison is made between two treatment methods: Risperidon and exposure and
response prevention. Dropout rates and side effects are included. In 2 groups
of 40 patients, assuming a SD of 6 and correlation of .78 between baseline and
end of treatment, the power needed for a difference of 2 points between the two
groups is .65, for a difference of 2.5 .84 and .94 for a difference of 3 points
by analysis with ANCOVA, with baseline YGTSS scores as covariates included. The
YGTSS will be the primary outcome measure; the (two-tailed) level of
significance will be set at p<0.05.
Intervention
Randomization starts after the in- and exclusion criteria are checked.
Stratification is applied for patients under and above 18 years of age.
There are two treatment conditions:
1) Exposure and Response Prevention (ERP);
2) Risperidone
Treatment starts 2 weeks after inclusion so a baseline of home tic registration
will be available. The ERP condition consists of 12 sessions of 1 hour. In the
first two training sessions, patients are taught to systematically suppress
their tics (i.e. response prevention). In the 10 consequent sessions, exposure
takes place to the unpleasant sensory sensation, which often precedes the
actual tic. By withholding the tic, patients learn to tolerate (or habituate
to) the sensory sensations. The therapist encourages the patient to suppress
all tics and at the same time keep concentration on the premonitory sensations
and the corresponding location in their
body. During sessions, information is gathered on the existence, anatomical
location, character and severity of premonitory sensations and urges. Every
five minutes, the severity of these sensations is asked for on a five-points
scale, and pointed out in a graphic. The occurrence of each motor or vocal tic
that has not been suppressed is registered. Integrity of treatment is
guaranteed by the use of treatment protocols (Verdellen et al, 2004b),
intensive training and supervision of therapists and monitoring of videotaped
sessions. The effect of ERP has been proven in one randomized controlled trial
and some case studies (for a review, see Cook& Blacher, 2007)
The medication condition consist of a flexible dose of risperidone, 2-6 mg a
day. Patients in the medication arm will be weekly contacted to get information
about effects and side effects. Integrity of treatment is guaranteed by a
compliance check with use of a blood draw after 6 weeks. The effect of
risperidone has been proven in different studies as well (for a review, see
Cath et al., 2008).
Study burden and risks
There are no risks in participation, the only burden is the extra time that is
needed for measurements. As far as possible, measurements by independent
assessors will be planned when patients have to come for treatment anyway.
Furthermore blood draw as a part of compliance check and taping sessions can be
felt as a burden. Treatment itself won't cause burden or risks because both
treatment conditions are proven to be effective treatment in these illnesses.
If patients don't participate in the research they will be offered one of the
two treatments.
Leyweg 275
2545 CH Den Haag
NL
Leyweg 275
2545 CH Den Haag
NL
Listed location countries
Age
Inclusion criteria
Patients have to meet DSM-IV criteria for GTS or CTD, and will be included according to the Diagnostic Confidence Index. Both children and adults are included, ranging from 6 to 65 years of age. Written informed consent is necessary to participate in the study by the patient. In case the patient is under age of 16 a written consent of parents is necessary before a patient is included in the study.
Exclusion criteria
Exclusion criteria are: severe major depression, psychosis, addiction, mental deficiency, known cardiovascular disease, family history of QT prolongation, bradycardia, other medication known to prolong QT interval, and inability to read/ speak Dutch. Exclusion criteria will be established
using the Mini International Neuropsychiatric Interview for adults, or the KIDDIE-SADS for children.Patients need to be free of antipsychotic medication for at least four weeks prior to entering the study.
Design
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-011134-96-NL |
| CCMO | NL27245.098.09 |