A Randomized, Double‐Blind, Placebo‐Controlled Study to Determine the Safety and Efficacy of Cultured and Expanded Autologous Fibroblast Injections for the Treatment of Interdental Papillary Insufficiency Associated With the Papilla Priming Procedure

Abstract

The aim of this study was to assess the efficacy and safety of using autologous fibroblast injections following a minimally invasive papilla priming procedure to augment open interproximal spaces. Twenty-one patients with open interproximal spaces were enrolled in this study, with 20 patients retained to study completion. Two primary sites were selected and randomized to receive autologous fibroblast injections or placebo injections beginning 1 week following the papilla priming procedure; two additional injections were performed 7 to 14 days following the initial injections. Up to seven additional sites could be treated per patient, and the analyses were conducted for the primary and secondary sites. The primary efficacy parameter was the percentage change in papillary height of the primary treatment areas from baseline to the 4-month visit, as measured by a periodontal probe from the base of the contact area to the tip of the interproximal papilla. Digital image analysis and diagnostic models were used to confirm clinical measurements. A visual analog scale (VAS) was used by the examiner and subject to assess the defect change from baseline to 2, 3, and 4 months. Tissue texture also was assessed by the examiner. The primary efficacy analysis failed to show a significant treatment effect at 4 months, but the treatment areas showed a statistically significant mean percentage increase from baseline in papillary height (P = 0.0067; signed-rank test) at 2 months. The difference between test and placebo sites in papillary height at 2 months approached statistical significance (P = 0.0730), suggesting that the test treatment was superior to the placebo treatment. The examiner and subject VASs were statistically significantly different from baseline for both treatment groups, and the VAS was superior for the test sites over the placebo. Based on safety data, the test treatment was deemed safe. This early-phase study using cell transplantation of autologous cultured and expanded fibroblasts following a papilla priming procedure suggests that the treatment is safe and may be efficacious for treating papillary insufficiency, especially in the early phases (2 months) of healing. The analysis of the investigator and subject VAS assessments indicates that the test treatment was superior to the placebo treatment. The finite measurement required to detect a change creates a problem that needs to be addressed in future studies.