骨内欠損を伴う重度歯周炎に対するレグロス® とシトランス® グラニュールの併用療法の安全性と有効性を評価する探索的臨床試験

An exploratory clinical trial to evaluate the safety and efficacy of combination therapy of REGROTH® and Cytrans® granules for severe periodontitis with intrabony defects.

抄録

はじめに:

現在，本邦における歯周組織再生療法は，REGROTH® （0.3% basic fibroblast growth factor［FGF-2］）を用いたflap operation（FOP）が標準治療法となっている．しかし，重度の歯槽骨欠損に対しては，REGROTH®単独療法による歯周組織再生効果は不十分である．そこで本研究では，REGROTH®（被験薬）と新規人工骨であるシトランス®顆粒（被験デバイス：炭酸アパタイト顆粒）を併用し，重度歯周炎患者に対する歯周再生療法の安全性と有効性を検討した．

Introduction: Currently, flap operation (FOP) using REGROTH® (0.3% basic fibroblast growth factor [FGF-2]) is the standard treatment for periodontal regenerative therapy in Japan. However, the periodontal tissue regenerative effect with REGROTH® monotherapy is inadequate for severe alveolar bone defects. Therefore, in this study, we evaluated the safety and effectiveness of periodontal regenerative therapy for patients with severe periodontitis using REGROTH® (test medicine) combined with Cytrans® Granules (test device: carbonated apatite granules), which is a new artificial bone.

研究方法:

対象は、重度歯周炎患者10名（平均年齢47.4歳）である。全員からインフォームドコンセントを得た。各患者の骨内欠損部位（平均骨欠損深さ：5.7mm）を試験部位とした。試験部位は，ベースライン調査後にFOPを実施し，試験薬と試験器具を同時に投与した．さらに、被験者の全身状態および試験部位の観察を行い、FOP 後 36 週間まで血液、尿、歯周組織検査を実施した。歯周組織検査では，骨増加率（％），臨床的付着レベル（CAL），プロービングポケット深さ（PPD），プロービング時出血（BOP），歯の動揺度（Mo），角化歯肉幅（KG），歯肉退縮（REC），歯肉指数（GI），歯垢指数（PlI）が評価された．

Methods: The study participants included 10 patients with severe periodontitis (mean age: 47.4 years). All participants provided written informed consents. In each patient, the intrabony defect site (mean bone defect depth: 5.7 mm) was defined as the test site. FOP was performed for the test site after the baseline investigation; moreover, the test medicine and test device were administered simultaneously. Furthermore, the observation of subjects' general condition and test sites was conducted and the blood, urine, and periodontal tissue tests were performed up to 36 weeks after FOP. The rate of bone increase (%), clinical attachment level (CAL), probing pocket depth (PPD), bleeding on probing (BOP), tooth mobility (Mo), width of keratinized gingiva (KG), gingival recession (REC), gingival index (GI), and plaque index (PlI) were evaluated during the periodontal tissue investigation.

結果:

主要評価項目として、本試験の全観察期間において、被験薬および被験機器に関連する有害事象は認められなかった。副次的評価項目については、試験薬および試験装置投与後 36 週間において、術前と比較して歯槽骨新生量（p=0.003）、CAL 取得量（p=0.001）、および PPD（p=0.002） と BOP（p=0.016） の減少が有意に増加した。さらに、術後36週では、Mo、GI、PlIはそれぞれ40％、60％、30％の部位で術前値まで低下していた。しかし，KG，RECについては術後36週で術前値との差は認められなかった．

Results: As the primary endpoint, no adverse events related to the test medicine and test device occurred during the entire observation period of this study. Regarding the secondary endpoints, there was a significant increase in new alveolar bone (p = 0.003) and CAL acquisition (p = 0.001) as well as decrease in PPD (p = 0.002) and BOP (p = 0.016) at 36 weeks after administration of the test medicine and test device compared with the preoperative values. Furthermore, at 36 weeks after surgery, the Mo, GI, and PlI decreased to preoperative levels at 40%, 60%, and 30% of sites, respectively. However, at 36 weeks after surgery, there was no difference in KG and REC compared with their preoperative values.

結論:

試験薬と上記試験装置を併用した歯周再生療法の安全性が確認された。本臨床試験は、日本臨床試験登録機構（jRCTs051190045）に特定臨床試験として登録・公示の上、実施した。

Conclusions: The safety of periodontal regenerative therapy using the test medicine in combination with the abovementioned test device was confirmed. In addition, it was suggested that this periodontal regenerative therapy is effective for tissue regeneration in severe alveolar bone defects.This clinical trial was conducted after registering and publicizing as a specified clinical trial in the Japan registry of clinical trials (jRCTs051190045).