title: Effect of heat shock protein peptide DiaPep277 on beta-cell function in paediatric and adult patients with recent-onset diabetes mellitus type 1: two prospective, randomized, double-blind phase II trials.
abstract: BACKGROUND
  Aim of this trial was to test whether heat shock protein peptide DiaPep277 treatment in adult and paediatric patients with recent-onset type 1 diabetes (T1D) is safe and whether it can preserve endogenous insulin production.
  
  
  METHODS
  Two studies were performed in a prospective, multicentre, double-blind, placebo-controlled trial. Fifty adult (study p520, aged 16-44 years) and 49 paediatric patients (study p521, 4-15 years) with recent-onset T1D were treated subcutaneously at four different time points with 0.2 mg or 1.0 mg DiaPep277 versus placebo and followed for 18 months. Adult patients were treated with 0.2 mg, 1.0 mg or 2.5 mg DiaPep277 versus placebo. Stimulated C-peptide served as readout for functional beta-cell-mass.
  
  
  RESULTS
  DiaPep277-treatment was not associated with severe side effects. No differences were found in placebo and DiaPep277 treated groups. In adults, a modest trend towards better maintenance of beta-cell function was observed in the 0.2 mg and 1.0 mg group, while there was significant loss of stimulated C-peptide in the placebo and 2.5 mg group. Paediatric patients with low HLA risk showed stable C-peptide levels until 13 months upon treatment with 1 mg DiaPep277. Despite similar stimulated C-peptide levels at baseline, children exhibited a more pronounced loss of beta-cell function over 18 months than adults (p = 0.0003).
  
  
  CONCLUSIONS
  Administration of DiaPep277 seems safe and may have beneficial effects on C-peptide levels over time in some patients with T1D, but this finding was not accompanied by reduced HbA1c or insulin requirement. Studies with more patients and longer follow-up are needed to further study the effect of DiaPep277.
authors.affiliation: German Diabetes Clinic, German Diabetes Center, Leibniz Institute at the Heinrich-Heine-University, Düsseldorf, Germany. schloot@ddz.uni-duesseldorf.de
authors.forename: Nanette C
authors.initials: NC
authors.lastname: Schloot
authors.forename: Guido
authors.initials: G
authors.lastname: Meierhoff
authors.forename: Csaba
authors.initials: C
authors.lastname: Lengyel
authors.forename: Gyözö
authors.initials: G
authors.lastname: Vándorfi
authors.forename: József
authors.initials: J
authors.lastname: Takács
authors.forename: Pál
authors.initials: P
authors.lastname: Pánczél
authors.forename: László
authors.initials: L
authors.lastname: Barkai
authors.forename: László
authors.initials: L
authors.lastname: Madácsy
authors.forename: Tamás
authors.initials: T
authors.lastname: Oroszlán
authors.forename: Peter
authors.initials: P
authors.lastname: Kovács
authors.forename: Gábor
authors.initials: G
authors.lastname: Sütö
authors.forename: Tadej
authors.initials: T
authors.lastname: Battelino
authors.forename: Nora
authors.initials: N
authors.lastname: Hosszufalusi
authors.forename: György
authors.initials: G
authors.lastname: Jermendy
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood; D002096:C-Peptide / Q000097:blood; D018834:Chaperonin 60; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D006442:Glycated Hemoglobin / Q000378:metabolism; D006680:HLA Antigens / Q000097:blood / Q000145:classification; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D007515:Islets of Langerhans / Q000276:immunology; D010446:Peptide Fragments; D010455:Peptides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D001323:Autoantibodies; D002096:C-Peptide; D018834:Chaperonin 60; D006442:Glycated Hemoglobin; D006680:HLA Antigens; D007004:Hypoglycemic Agents; D007328:Insulin; D010446:Peptide Fragments; D010455:Peptides; C447781:DiaPep 277