title: Trichuris suis ova in relapsing-remitting multiple sclerosis and clinically isolated syndrome (TRIOMS): study protocol for a randomized controlled trial.
abstract: BACKGROUND
  Trichuris suis ova is a probiotic treatment based on the hygiene hypothesis. It has been demonstrated as safe and effective in autoimmune inflammatory bowel diseases and clinical trials indicate that helminth infections also have an immunomodulatory effect in multiple sclerosis.We hypothesize that administering 2,500 Trichuris suis ova eggs orally every two weeks for 12 months is--due to its immunomodulatory and anti-inflammatory effect--significantly more effective than oral placebo in preventing new T2 and Gd+ lesions, as quantified by cerebral MRI and clinical examination, in relapsing-remitting multiple sclerosis and clinically isolated syndrome.
  
  
  METHODS
  Fifty patients with relapsing-remitting multiple sclerosis or clinically isolated syndrome with clinical activity, not undergoing any standard therapies, will be randomized 1:1 to Trichuris suis ova 2,500 eggs every two weeks or matching placebo. The safety, tolerability and effect on disease activity and in vivo mechanisms of action of Trichuris suis ova in MS will be assessed by neurological, laboratory and immunological exams and magnetic resonance imaging throughout the 12-month treatment period and over a follow-up period of 6 months. Various immunological analyses will be used to assess the overall patient immune response prior to and at varying time points following treatment with Trichuris suis ova.
  
  
  CONCLUSIONS
  We anticipate that Trichuris suis ova will be well tolerated and more effective than the placebo in preventing new T2 and Gd+ lesions, as quantified by MRI. We also expect the Th1/Th17 proinflammatory response to shift towards the more anti-inflammatory Th2 response. This study has important clinical implications and will involve extensive research on the immunology of helminth therapy.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT01413243.
authors.affiliation: Department of Neurology and Experimental Neurology, Charité - Universitätsmedizin Berlin, Charitéplatz 1, Berlin 10117, Germany. berit.rosche@charite.de
authors.forename: Berit
authors.initials: B
authors.lastname: Rosche
authors.forename: Klaus-Dieter
authors.initials: KD
authors.lastname: Wernecke
authors.forename: Stephanie
authors.initials: S
authors.lastname: Ohlraun
authors.forename: Jan-Markus
authors.initials: JM
authors.lastname: Dörr
authors.forename: Friedemann
authors.initials: F
authors.lastname: Paul
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002985:Clinical Protocols; D003711:Demyelinating Diseases / Q000175:diagnosis / Q000276:immunology / Q000628:therapy*; D005858:Germany; D006801:Humans; D008279:Magnetic Resonance Imaging; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis / Q000276:immunology / Q000628:therapy*; D010063:Ovum / Q000276:immunology; D010808:Physical Examination; D011237:Predictive Value of Tests; D019936:Probiotics / Q000009:adverse effects / Q000627:therapeutic use*; D012107:Research Design; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D061147:Therapy with Helminths / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D014258:Trichuris / Q000254:growth & development / Q000276:immunology*