title: Safety and clinical effects of topical histatin gels in humans with experimental gingivitis.
abstract: BACKGROUND
  Our research group has recently reported that exogenously applied histatins can inhibit plaque accumulation and gingival inflammation in a preclinical canine model (Paquette et al. 1997).
  
  
  OBJECTIVE
  The aims of the present double-blinded, randomized, controlled clinical trial were to evaluate the safety and toxicity of three histatin (P-113) concentrations in gel formulations, and to assess potential clinical benefit on the development of gingivitis (partial mouth design).
  
  
  METHODS
  One hundred and six healthy subjects were recruited and brought to optimal gingival health (GI < 0.5) prior to treatment initiation. At baseline, eligible subjects were randomized for one of the following treatments: (1) placebo; (2) 0.0625% P-113; (3) 0.125% P-113; and (4) 0.375% P-113. Patients self-applied gels twice daily for 29 days to the maxillary right quadrant with the use of customized stents. In addition, patients deferred all oral hygiene procedures within this quadrant for the duration of the treatment period. Safety was assessed in terms of physical and oral examinations, clinical laboratory testing and recording of adverse events. Clinical indices were measured weekly and included gingival index (GI), plaque index (PI) and %BOP.
  
  
  RESULTS
  All study formulations were well tolerated by patients, and no differences in adverse event occurrences were noted among treatment groups, including taste alteration or staining. For the intent-to-treat population, significantly smaller %BOP changes were noted in subjects treated with 0.0625, 0.125 and 0.375% P-113 gels (17.4, 18.18 and 17.9%, respectively) versus placebo (28.0%) (p < 0.05) at day 29. When groups were compared in terms of per cent responders (change in %BOP < 15 or < 20%), P-113 treatment groups exhibited a higher frequency of response, especially for the 0.0625 and 0.125% P-113 formulations (p < 0.05). Although no statistically significant intergroup differences were noted for changes in GI or PI among all subjects (intent-to-treat population), significantly smaller changes in PI at day 22 were observed among compliant individuals (defined as subjects using > 60% of the target gel mass) administering P-113 gels as compared with compliant placebo subjects (p < 0.05).
  
  
  CONCLUSIONS
  These data indicate safety and tolerance of P-113 gels for topical oral use in human subjects. These data also suggest that P-113 gels administered twice daily may reduce experimental gingivitis as measured with bleeding on probing in humans.
authors.affiliation: Department of Periodontology, Comprehensive Center for Inflammatory Disorders, School of Dentistry, University of North Carolina at Chapel Hill, USA. David_Paquette@dentistry.unc.edu
authors.forename: D W
authors.initials: DW
authors.lastname: Paquette
authors.forename: D M
authors.initials: DM
authors.lastname: Simpson
authors.forename: P
authors.initials: P
authors.lastname: Friden
authors.forename: V
authors.initials: V
authors.lastname: Braman
authors.forename: R C
authors.initials: RC
authors.lastname: Williams
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000891:Anti-Infective Agents, Local / Q000008:administration & dosage* / Q000633:toxicity; D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage* / Q000633:toxicity; D016009:Chi-Square Distribution; D003257:Consumer Product Safety; D003773:Dental Plaque / Q000517:prevention & control*; D003774:Dental Plaque Index; D004311:Double-Blind Method; D004361:Drug Tolerance; D005260:Female; D005782:Gels; D005891:Gingivitis / Q000188:drug therapy*; D006801:Humans; D008297:Male; D010512:Periodontal Index; D011506:Proteins / Q000008:administration & dosage* / Q000633:toxicity; D012471:Salivary Proteins and Peptides / Q000008:administration & dosage* / Q000633:toxicity; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D000099053:Histidine-Rich Glycoprotein
chemical_list: D000891:Anti-Infective Agents, Local; D023181:Antimicrobial Cationic Peptides; D005782:Gels; D011506:Proteins; D012471:Salivary Proteins and Peptides; D000099053:Histidine-Rich Glycoprotein