title: Two randomized controlled clinical trials to study the effectiveness of prednisolone treatment in preventing and restoring clinical nerve function loss in leprosy: the TENLEP study protocols.
abstract: BACKGROUND
  Nerve damage in leprosy often causes disabilities and deformities. Prednisolone is used to treat nerve function impairment (NFI). However, optimal dose and duration of prednisolone treatment has not been established yet. Besides treating existing NFI it would be desirable to prevent NFI. Studies show that before NFI is clinically detectable, nerves often show subclinical damage. Within the 'Treatment of Early Neuropathy in LEProsy' (TENLEP) study two double blind randomized controlled trials (RCT) will be carried out: a trial to establish whether prednisolone treatment of 32 weeks duration is more effective than 20 weeks in restoring nerve function in leprosy patients with clinical NFI (Clinical trial) and a trial to determine whether prednisolone treatment of early sub-clinical NFI can prevent clinical NFI (Subclinical trial).
  
  
  METHODS
  Two RCTs with a follow up of 18 months will be conducted in six centers in Asia. In the Clinical trial leprosy patients with recent (< 6 months) clinical NFI, as determined by Monofilament Test and Voluntary Muscle Test, are included. The primary outcomes are the proportion of patients with restored or improved nerve function. In the Subclinical trial leprosy patients with subclinical neuropathy, as determined by Nerve Conduction Studies (NCS) and/or Warm Detection Threshold (WDT), and without any clinical signs of NFI are randomly allocated to a placebo group or treatment group receiving 20 weeks prednisolone. The primary outcome is the proportion of patients developing clinical NFI. Reliability and normative studies are carried out before the start of the trial.
  
  
  CONCLUSIONS
  This study is the first RCT testing a prednisolone regimen with a duration longer than 24 weeks. Also it is the first RCT assessing the effect of prednisolone in the prevention of clinical NFI in patients with established subclinical neuropathy. The TENLEP study will add to the current understanding of neuropathy due to leprosy and provide insight in the effectiveness of prednisolone on the prevention and recovery of NFI in leprosy patients. In this paper we present the research protocols for both Clinical and Subclinical trials and discuss the possible findings and implications.
  
  
  BACKGROUND
  Netherlands Trial Register: NTR2300 Clinical Trial Registry India: CTRI/2011/09/002022.
authors.affiliation: Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. i.wagenaar@erasmusmc.nl
authors.forename: Inge
authors.initials: I
authors.lastname: Wagenaar
authors.forename: Wim
authors.initials: W
authors.lastname: Brandsma
authors.forename: Erik
authors.initials: E
authors.lastname: Post
authors.forename: Wim
authors.initials: W
authors.lastname: van Brakel
authors.forename: Diana
authors.initials: D
authors.lastname: Lockwood
authors.forename: Peter
authors.initials: P
authors.lastname: Nicholls
authors.forename: Paul
authors.initials: P
authors.lastname: Saunderson
authors.forename: Cairns
authors.initials: C
authors.lastname: Smith
authors.forename: Einar
authors.initials: E
authors.lastname: Wilder-Smith
authors.forename: Jan Hendrik
authors.initials: JH
authors.lastname: Richardus
mesh_terms: D000293:Adolescent; D000328:Adult; D002985:Clinical Protocols; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007918:Leprosy / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy* / Q000209:etiology; D011239:Prednisolone / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D005938:Glucocorticoids; D011239:Prednisolone