Effects of Short-Term COL-3 on Local Biomarkers of Periodontitis

Host modulatory therapy has been developed for the management of periodontal diseases based on a sub-antimicrobial dose of doxycycline (Periostat). A non-antimicrobial derivative of tetracycline, 6-deoxy-6-demethyl-4-dedimethylamino tetracycline, known as COL-3 (also reported in the literature as CMT-3 or Incyclinide) may provide a new therapeutic option for patients with periodontitis. Objectives: The purpose of this randomized clinical trial was to determine if COL-3 was capable of reducing ginigival crevicular fluid enzymes and cytokines in sites with excessive collagenase activity. Methods: 35 subjects were enrolled in a double-blind, placebo controlled study. All subjects received pre-screening debridement and were subsequently screened for elevated collagenase activity (>10%) at two consecutive visits in at least 2 sites over 4 weeks. The subjects were then randomized to receive either orally administered COL-3 (10mg q.d.; n=18) or placebo (n=17) capsules for 1 month followed by a month long wash out period. A minimum of 2 sites/subject were analyzed for collagenase activity by HPLC and Western Blot analysis and IL-1β by ELISA from baseline to month 2. Results: Sites in subjects treated with COL-3 experienced 31.73, 53.40, 55.56 percent reduction in IL-1β (pg/site), PMN pro- and active MMP-8 forms as compared to 11.33, 23.28, 2.55 percent reductions in sites treated in the placebo group, respectively. No changes were noted in the mesenchymal form of collagenase MMP-8 and MMP-13. No SAEs were reported. Conclusions: Oral administration of COL-3 for 1 month at 10mg q.d. resulted in reductions in enzyme and cytokine activity in active sites for a period of two months beyond what was seen in the placebo group. Supported by CollaGenex Pharmaceuticals Inc, Newtwon, PA and conducted at Stony Brook University Hospital GCRC (M01RR10710). The study was approved by the Stony Brook University GAC (03-213-67) and CORHIS (20045260) and the FDA (IND 63,956).