Efficacy of Amoxicilline/Clavulanic Acid in Patients Affected by Tic Disorder Colonized by Group A Streptococcus

NCT01860300 | Unknown DMC

• 2 other identifiers: Sapienza Università di Roma2012-002430-36
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief 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GAS infection or who otherwise need to be prescribed antibiotics for any clinical reason during the follow-up will be withdrawn from the study and immediately deblinded.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.

Conditions

Tic Disorders

Keywords

Tic Disorders; Tourette Syndrome

Outcome Measures

Primary Outcomes (1)

• Severity of tic disorder

  YGTSS scores

  one month

Secondary Outcomes (1)

• Severity of tic disorder

  one year

Other Outcomes (1)

• Severity of associated neuropsychiatric symptoms

  one month - one year

Study Arms (2)

Antibiotic

EXPERIMENTAL

Amoxicillin-Potassium Clavulanate Combination

Drug: Amoxicillin-Potassium Clavulanate Combination

Placebo

PLACEBO COMPARATOR

Placebo

Drug: placebo

Interventions

Amoxicillin-Potassium Clavulanate Combination DRUG

Amoxicillin-Potassium Clavulanate Combination will be prescribed at the dose of 25/3.6 mg/kg/day for 10 days, 2 times/day, as oral suspension.

Also known as: Augmentin

Antibiotic

placebo DRUG

Placebo

Eligibility Criteria

• Age: 3 Years - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Roma La Sapienza: lead

Study Sites (1)

Department of Pediatrics and Child Neuropsychiatry

Rome, 00185, Italy

RECRUITING

Related Publications (15)

• Bombaci M, Grifantini R, Mora M, Reguzzi V, Petracca R, Meoni E, Balloni S, Zingaretti C, Falugi F, Manetti AG, Margarit I, Musser JM, Cardona F, Orefici G, Grandi G, Bensi G. Protein array profiling of tic patient sera reveals a broad range and enhanced immune response against Group A Streptococcus antigens. PLoS One. 2009 Jul 22;4(7):e6332. doi: 10.1371/journal.pone.0006332.

  PMID: 19623252 BACKGROUND

• Cardona F, Orefici G. Group A streptococcal infections and tic disorders in an Italian pediatric population. J Pediatr. 2001 Jan;138(1):71-5. doi: 10.1067/mpd.2001.110325.

  PMID: 11148515 BACKGROUND

• Church AJ, Dale RC, Lees AJ, Giovannoni G, Robertson MM. Tourette's syndrome: a cross sectional study to examine the PANDAS hypothesis. J Neurol Neurosurg Psychiatry. 2003 May;74(5):602-7. doi: 10.1136/jnnp.74.5.602.

  PMID: 12700302 BACKGROUND

• Creti R, Cardona F, Pataracchia M, Hunolstein CV, Cundari G, Romano A, Orefici G. Characterisation of group A streptococcal (GAS) isolates from children with tic disorders. Indian J Med Res. 2004 May;119 Suppl:174-8.

  PMID: 15232189 BACKGROUND

• Curtin-Wirt C, Casey JR, Murray PC, Cleary CT, Hoeger WJ, Marsocci SM, Murphy ML, Francis AB, Pichichero ME. Efficacy of penicillin vs. amoxicillin in children with group A beta hemolytic streptococcal tonsillopharyngitis. Clin Pediatr (Phila). 2003 Apr;42(3):219-25. doi: 10.1177/000992280304200305.

  PMID: 12739920 BACKGROUND

• Garvey MA, Perlmutter SJ, Allen AJ, Hamburger S, Lougee L, Leonard HL, Witowski ME, Dubbert B, Swedo SE. A pilot study of penicillin prophylaxis for neuropsychiatric exacerbations triggered by streptococcal infections. Biol Psychiatry. 1999 Jun 15;45(12):1564-71. doi: 10.1016/s0006-3223(99)00020-7.

  PMID: 10376116 BACKGROUND

• Kaplan EL, Johnson DR. Eradication of group A streptococci from the upper respiratory tract by amoxicillin with clavulanate after oral penicillin V treatment failure. J Pediatr. 1988 Aug;113(2):400-3. doi: 10.1016/s0022-3476(88)80291-9. No abstract available.

  PMID: 3135377 BACKGROUND

• Loiselle CR, Wendlandt JT, Rohde CA, Singer HS. Antistreptococcal, neuronal, and nuclear antibodies in Tourette syndrome. Pediatr Neurol. 2003 Feb;28(2):119-25. doi: 10.1016/s0887-8994(02)00507-6.

  PMID: 12699862 BACKGROUND

• Mahakit P, Vicente JG, Butt DI, Angeli G, Bansal S, Zambrano D. Oral clindamycin 300 mg BID compared with oral amoxicillin/clavulanic acid 1 g BID in the outpatient treatment of acute recurrent pharyngotonsillitis caused by group a beta-hemolytic streptococci: an international, multicenter, randomized, investigator-blinded, prospective trial in patients between the ages of 12 and 60 years. Clin Ther. 2006 Jan;28(1):99-109. doi: 10.1016/j.clinthera.2006.01.006.

  PMID: 16490583 BACKGROUND

• Martino D, Church AJ, Defazio G, Dale RC, Quinn NP, Robertson MM, Livrea P, Orth M, Giovannoni G. Soluble adhesion molecules in Gilles de la Tourette's syndrome. J Neurol Sci. 2005 Jul 15;234(1-2):79-85. doi: 10.1016/j.jns.2005.03.032.

  PMID: 15941572 BACKGROUND

• Martino D, Chiarotti F, Buttiglione M, Cardona F, Creti R, Nardocci N, Orefici G, Veneselli E, Rizzo R; Italian Tourette Syndrome Study Group. The relationship between group A streptococcal infections and Tourette syndrome: a study on a large service-based cohort. Dev Med Child Neurol. 2011 Oct;53(10):951-7. doi: 10.1111/j.1469-8749.2011.04018.x. Epub 2011 Jun 17.

  PMID: 21679362 BACKGROUND

• Morshed SA, Parveen S, Leckman JF, Mercadante MT, Bittencourt Kiss MH, Miguel EC, Arman A, Yazgan Y, Fujii T, Paul S, Peterson BS, Zhang H, King RA, Scahill L, Lombroso PJ. Antibodies against neural, nuclear, cytoskeletal, and streptococcal epitopes in children and adults with Tourette's syndrome, Sydenham's chorea, and autoimmune disorders. Biol Psychiatry. 2001 Oct 15;50(8):566-77. doi: 10.1016/s0006-3223(01)01096-4.

  PMID: 11690591 BACKGROUND

• Muller N, Kroll B, Schwarz MJ, Riedel M, Straube A, Lutticken R, Reinert RR, Reineke T, Kuhnemund O. Increased titers of antibodies against streptococcal M12 and M19 proteins in patients with Tourette's syndrome. Psychiatry Res. 2001 Mar 25;101(2):187-93. doi: 10.1016/s0165-1781(01)00215-3.

  PMID: 11286821 BACKGROUND

• Rizzo R, Gulisano M, Pavone P, Fogliani F, Robertson MM. Increased antistreptococcal antibody titers and anti-basal ganglia antibodies in patients with Tourette syndrome: controlled cross-sectional study. J Child Neurol. 2006 Sep;21(9):747-53. doi: 10.1177/08830738060210091001.

  PMID: 16970879 BACKGROUND

• Snider LA, Lougee L, Slattery M, Grant P, Swedo SE. Antibiotic prophylaxis with azithromycin or penicillin for childhood-onset neuropsychiatric disorders. Biol Psychiatry. 2005 Apr 1;57(7):788-92. doi: 10.1016/j.biopsych.2004.12.035.

  PMID: 15820236 BACKGROUND

MeSH Terms

Conditions

Tic Disorders; Tourette Syndrome

Interventions

Amoxicillin-Potassium Clavulanate Combination

Condition Hierarchy (Ancestors)

Movement Disorders; Central Nervous System Diseases; Nervous System Diseases; Neurodevelopmental Disorders; Mental Disorders; Basal Ganglia Diseases; Brain Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Clavulanic Acid; Clavulanic Acids; beta-Lactams; Lactams; Amides; Organic Chemicals; Amoxicillin; Ampicillin; Penicillin G; Penicillins; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Francesco Cardona, MD

  Sapienza Università di Roma

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Francesco Cardona, MD

CONTACT

+390644712288; francesco.cardona@uniroma1.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: May 19, 2013
• First Posted: May 22, 2013
• Study Start: March 1, 2013
• Primary Completion: April 1, 2017
• Study Completion: May 1, 2017
• Last Updated: May 11, 2016

Record last verified: 2016-05

Locations

IT (1)