Multicentre, randomised, double-blinded, placebo-controlled trial of efficacy of amoxicilline/clavulanic acid in patients affected by tic disorder colonized by GAS. No-proft stidy.

The aetiology of tic disorders and associated obsessive-compulsive and
behavioural symptoms is poorly understood. It has been postulated that genetic
and environmental factors active upon regulatory systems (e.g. immune and
endocrine systems) might interact in creating a neurobiological vulnerability
to the development of tics and associated behaviours. The largest body of
evidence from clinical research has been gathered in support of a role of
exposure to psychosocial stress, of pregnancy and delivery adversities and of
infections from GAS (Murphy, Kurlan, and Leckman, 2010). The human pathogen GAS
is a major cause of common pharyngitis, but also of significant
post-streptococcal non-suppurative autoimmune multi-organ sequelae associated
with the existence of host autoantibodies against GAS antigens (also known as
the Paediatric Autoimmune Neuropsychiatric Disorders Associated with
Streptococcal Infections [PANDAS]-hypothesis). It has been hypothesized 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.

This study is an extension of the European Multicenter Tics in Children Studies
(EMTICS) Course study for which a separate study protocol exists; its aim is to
verify the efficacy of GAS colonization treatment on tic symptoms in term of
severity. The primary objective is to 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. The secondary
objective is to 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.

Multicentre, randomised, double-blinded, placebo-controlled trial. In
AntibioTICS, European sites together will recruit 72 children, of which the
UMCG will recruit 4 children participating in the EMTICS COURSE study. EMTICS
is a longitudinal observational European multicenter study consisting of an
ONSET and COURSE study part. European sites together will recruit 700 children
in the COURSE study, of which the UMCG will recruit 60 children, thus of which
5 children shall take part in AntibioTICS.

Amoxicilline/clavulanic acid, Oral suspension, 25/3.6 mg/kg/day, oral, over the
course of 10 days two times daily.

The burden for the child will be the use of two daily doses of antibiotics or
placebo for 10 consecutive days. Further, there will be four visits at the
clinical center (4 x 60 minutes), completion of parent-questionnaires before
the visits (4 x 20 minutes) and a short child-questionnaires (4 x 5-10
minutes), and completion of a weekly home diary by the parent (32 x 5 minutes
= 20 min), and two telephone interviews (2 x 20 minutes). At the visits, a
blood draw by venipuncture, throat swab and collection of hair strands will be
taken in the child. Risks and physical or physiological discomfort of these
measurements will be negligible or mild. Side effects of antibiotics may
involve nausea or dizziness. This research protocol includes the participation
of minors as tic disorders have a childhood onset and are most pronounced at
that age.