Efficacy of Amoxicilline/Clavulanic Acid in Patients Affected by Tic Disorder Colonized by Group A Streptococcus
Information source: University of Roma La Sapienza
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Tic Disorders
Intervention: Amoxicillin-Potassium Clavulanate Combination (Drug); placebo (Drug)
Phase: N/A
Status: Recruiting
Sponsored by: University of Roma La Sapienza Official(s) and/or principal investigator(s): Francesco Cardona, MD, Principal Investigator, Affiliation: Sapienza Università di Roma
Overall contact: Francesco Cardona, MD, Phone: +390644712288, Email: francesco.cardona@uniroma1.it
Summary
This study is an extension of the European Multicentre Tics In Children Studies (EMTICS)
COURSE study for which a separate study protocol exists; Aim of this clinical trial is to
study the efficacy of treatment with antibiotics in reducing severity of tics and associated
neuropsychiatric symptoms in patients with a tic disorder colonised by GAS.
Primary Objective: Test the hypothesis that antibiotic treatment of GAS colonisation
compared to placebo is associated with a larger reduction of tic and associated
neuropsychiatric symptoms in the short-term (1 month) in patients with a tic disorder
colonised by GAS.
Secondary Objective: Test the hypothesis that antibiotic treatment of GAS colonisation is
superior to placebo in the long-term (1 year) reduction of tic and associated
neuropsychiatric symptoms in patients with a tic disorder colonized by GAS.
Patients affected by a chronic tic disorder followed in the EMTICS- Longitudinal Course
Study that show a positive culture for GAS at any microbiological examination during their
follow-up will be considered eligible for the treatment trial.
Patients showing GAS positivity will be invited to participate in the clinical trial.
The patients enrolled will be randomly assigned to antibiotic or placebo in a 1: 1 ratio.
All participating patients will undergo a microbiological, serological and clinical
assessment 1 month after the date of entering in the treatment trial (i. e. around 20 days
after the end of treatment). Then, the patients will be followed with clinical, laboratory
and microbiological assessments every four months for 1 year.
Patients will be deblinded at the end of the treatment trial follow-up (1 year after the
recruitment).
Patients who will develop a true GAS infection or who otherwise need to be prescribed
antibiotics for any clinical reason during the follow-up will be withdrawn from the study
and immediately deblinded. Data of such patients would, however, remain part of the study
analyses, following the intention-to-treat principle.
Clinical Details
Official title: Multicentre, Randomised, Double-blinded, Placebo-controlled Trial of Efficacy of Amoxicilline/Clavulanic Acid in Patients Affected by Tic Disorder Colonized by Group A Streptococcus
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Severity of tic disorder
Secondary outcome: Severity of tic disorder
Detailed description:
Following the few studies performed on this topic, children affected by tic disorder show a
rate of Group A Streptococcus (GAS) colonization similar or slightly higher than that
reported in the normal population.
However, several studies have documented high rates of elevated anti-streptolysin O titers
(ASOT) in children affected by tic disorders. One study reported a significantly higher ASOT
in 150 children with tics compared to 150 healthy children, documenting a direct
relationship between ASOT and tic severity. In this study, however, throat swab culture
analyses on a subsample of patients failed to detect a predominant GAS serotype associated
with tics. An American cohort of 81 patients with TS also exhibited higher ASOT than
age-matched healthy volunteers and a mixed group of patients with autoimmune diseases.
Increased ASOT, anti-deoxyribonuclease B (DNAse B), anti- streptococcal M12 and M19 titres
were also observed in a smaller German sample of patients with TS. In a British cohort of
100 patients with TS (50% children), ASOT was raised in 64% of children and in 68% of adults
with TS; this was significantly higher than in neurological disease and healthy control
subjects. Two other reports from British and Italian cohorts confirmed these findings.
However, a subsequent study failed to find a significant association with ASOT and
anti-DNAse B titres using the same cross-sectional approach. More recently, a study on a
large service-based cohort of TS patients confirmed the significant elevated rate of the
high ASOT, but evidenced also that, on prospective analysis, ASOT were persistently elevated
in 57% of patients with TS. Moreover, in tic patients the enhanced immune response is not
limited to ASOT but it involves a broad range of GAS antigens.
Taken together, these observations lead to hypothesize that TS patients colonized by GAS are
not merely carriers and that this colonization may promote a sustained anti-streptococcal
immune response contributing to the persistence of tic symptoms.
If this hypothesis is true, the antibiotic treatment of GAS colonization in patients
affected by a chronic tic disorder could modify their symptoms in term of severity and
number of exacerbations.
Up to now, only tic patients diagnosed as Pediatric Autoimmune Neuropsychiatric Disorders
Associated with Streptococcal infection (PANDAS) underwent a controlled antibiotic
treatment: two trials, aimed to study the efficacy of different preventive regimens on
number of tic exacerbations, obtained however mixed results, mainly due to poor compliance.
Investigators here designed a placebo-controlled trial with amoxicilline/clavulanic acid in
tic patients showing GAS colonization. This drug is the first line therapy for streptococcal
pharyngo-tonsillitis. Some previous studies have shown a superiority of amoxicillin versus
penicillin in the treatment of GAS infections. A 10-day course of amoxicillin is considered
sufficient and efficient in the treatment of GAS tonsillo-pharyngitis. Moreover, oral
amoxicillin/clavulanic acid and oral clindamycin for 10 days achieved comparable rates of
bacteriologic eradication at 12 days and 3 months. Furthermore, amoxicilline/clavulanic acid
has been demonstrated to be efficacious in the treatment of GAS colonization. A few
antibiotic regimens - evaluated prospectively in randomized, controlled trials- have
demonstrated efficacy for termination of GAS carriage: among these, a regimen of 10 days of
amoxicillin/ clavulanic acid was more effective than repeat penicillin in patients with
treatment failure. Thus, the 10-days regimen of amoxicilline/clavulanic acid should be
efficient in GAS eradication and, on the other hand, the shortness of the treatment should
avert problems in patient's compliance.
Eligibility
Minimum age: 3 Years.
Maximum age: 16 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Diagnosis of Tourette Syndrome or another chronic tic disorder according to DSM IV-TR
criteria.
- Evidence of GAS colonization at any visit of EMTICS Longitudinal Course Study.
- Either no current psychotropic medication or on stable anti-tic medication for at
least 2 months before the enrolment in the trial.
- Able (in the Investigators opinion) and willing to comply with all study
requirements.
Exclusion Criteria:
- Children and/or parents are unable to understand and comply with protocol
- Any antibiotic treatment for any reason during the last month before enrolment in the
trial.
- Clinical manifestations of pharyngitis or other streptococcal infections at moment of
enrolment in the trial.
- Known or suspected hypersensitivity to penicillin or other β-lactam antibacterials, a
history of amoxicillin-clavulanate-associated cholestatic jaundice or hepatic
dysfunction.
- Known and/or suspected renal or hepatic impairment (due to the potential for
drug-related toxicity in patients with such a condition).
- Scheduled elective surgery or other procedures requiring general anaesthesia during
the study.
- Any other significant disease or disorder which, in the opinion of the Investigator,
may either put the participants at risk because of participation in the study, or may
influence the result of the study, or the participant's ability to participate in the
study.
- Participants who have participated in another research study involving an
investigational product in the past 12 weeks
Locations and Contacts
Francesco Cardona, MD, Phone: +390644712288, Email: francesco.cardona@uniroma1.it
Department of Pediatrics and Child Neuropsychiatry, Rome 00185, Italy; Recruiting Valeria Neri, MD, Sub-Investigator
Additional Information
Click here for more information about this study: www.emtics.eu
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Starting date: March 2013
Last updated: December 1, 2014
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