title: Botulinum neurotoxin type A in the treatment of classical Trigeminal Neuralgia (BoTN): study protocol for a randomized controlled trial.
abstract: BACKGROUND
  Trigeminal neuralgia is characterized by paroxysmal facial pain attacks. Adequate prophylactic drug therapy is often limited by the lack of efficacy and intolerance due to central nervous system side effects. Subcutaneous injections of botulinum toxin type A are a promising treatment option for patients with unsatisfactory response to drug therapy or neurosurgical intervention. Its effects are expected to last for at least 3 months, so it could be a potential long-term treatment. This is the study protocol of a prospective, placebo-controlled, double blind clinical trial investigating the add-on therapy of subcutaneous administration of botulinum toxin type A injections to standard treatment in therapy-refractory classical trigeminal neuralgia.
  
  
  METHODS
  BoTN is a prospective, double blind, placebo-controlled trial with a randomized withdrawal design in which a single blind phase is followed by a double blind phase (see also Methods and design). Eligible patients with classical trigeminal neuralgia who are otherwise refractory to medical and neurosurgical treatment will receive subcutaneous injections of botulinum toxin type A into injection sites of the affected trigeminal branch. In the first phase all patients will receive botulinum toxin type A in a single blinded intervention. Twelve weeks later therapy responders will be allocated to the verum or placebo (saline) arm in a double blind, randomized manner. These injections will be performed at the same sites as the first injections. This trial will be conducted in a tertiary outpatient clinic specialized in the treatment of headache and facial pain. There will be three investigators performing the injections who are experienced in the treatment of headache and facial pain and trained in botulinum toxin type A injections.
  
  
  CONCLUSIONS
  BoTN is designed to assess the efficacy and safety of subcutaneous botulinum toxin type A injections in addition to standard prophylactic treatment in therapy-refractory trigeminal neuralgia.
  
  
  BACKGROUND
  EU Clinical Trials Register: EudraCT-No: 2014-001959-24 https://www.clinicaltrialsregister.eu/ctr-search/rest/download/trial/2014-001959-24/DE Date of trial registration 26 August 2014.
authors.affiliation: Department of Neurology and Headache Center, University Hospital Essen, Hufelandstraße 55, 45122, Essen, Germany. jan.burmeister@uk-essen.del.
authors.forename: Jan
authors.initials: J
authors.lastname: Burmeister
authors.affiliation: Department of Neurology and Headache Center, University Hospital Essen, Hufelandstraße 55, 45122, Essen, Germany. dagny.holle@uk-essen.de.
authors.forename: Dagny
authors.initials: D
authors.lastname: Holle
authors.affiliation: Center for Clinical Trials, Essen (ZKSE) and Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University Hospital Essen, Hufelandstraße 55, 45122, Essen, Germany. eva.bock@uk-essen.de.
authors.forename: Eva
authors.initials: E
authors.lastname: Bock
authors.affiliation: Center for Clinical Trials, Essen (ZKSE) and Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University Hospital Essen, Hufelandstraße 55, 45122, Essen, Germany. claudia.ose@uk-essen.de.
authors.forename: Claudia
authors.initials: C
authors.lastname: Ose
authors.affiliation: Department of Neurology and Headache Center, University Hospital Essen, Hufelandstraße 55, 45122, Essen, Germany. hans.diener@uni-due.de.
authors.forename: Hans-Christoph
authors.initials: HC
authors.lastname: Diener
authors.affiliation: Department of Neurology and Headache Center, University Hospital Essen, Hufelandstraße 55, 45122, Essen, Germany. mark.obermann@uk-essen.de.
authors.forename: Mark
authors.initials: M
authors.lastname: Obermann
mesh_terms: D065087:Acetylcholine Release Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D000700:Analgesics / Q000008:administration & dosage* / Q000009:adverse effects; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage* / Q000009:adverse effects; D002985:Clinical Protocols; D004311:Double-Blind Method; D005157:Facial Pain / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D005858:Germany; D006261:Headache / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D006801:Humans; D007279:Injections, Subcutaneous; D009483:Neuropsychological Tests; D010147:Pain Measurement; D011446:Prospective Studies; D012107:Research Design; D016037:Single-Blind Method; D062606:Tertiary Care Centers; D013997:Time Factors; D016896:Treatment Outcome; D014277:Trigeminal Neuralgia / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology
chemical_list: D065087:Acetylcholine Release Inhibitors; D000700:Analgesics; D019274:Botulinum Toxins, Type A