Center for Clinical and Translational Research, The Forsyth Institute, Cambridge, MA, United States.
Department of Applied Oral Sciences, The Forsyth Institute, Cambridge, MA, United States.
Front Immunol. 2021 Sep 13;12:704163. doi: 10.3389/fimmu.2021.704163. eCollection 2021.
Periodontal disease is among the sixth most common inflammatory diseases worldwide with high risk to promote complications from other inflammatory diseases including diabetes, cardiovascular disease and Alzheimer's Disease. Failure of active resolution of inflammation pathways is implicated in pathogenesis of periodontal diseases, including gingivitis. Lipoxin A4 (LXA4), a member of the specialized pro-resolving lipid mediators (SPMs) that drive resolution of inflammation GPC-receptor mediated pathways, offered therapeutic advantages in preclinical models of periodontitis.
We conducted a randomized, placebo-controlled, parallel-group Phase 1 clinical trial to determine the safety and preliminary efficacy of an LXA4 analog in patients with gingival inflammation. One hundred twenty-seven (127) individuals were randomized to daily use of an oral rinse containing a LXA4 mimetic, methyl ester-benzo-lipoxin A4 (BLXA4), placebo rinse or a no-rinse control group for 28 days. Treatment emergent adverse events (TEAEs) were assessed for safety, the primary outcome. Secondary outcomes included the change in the level of gingival inflammation and periodontal pocket depth (PD). Serum SPMs were monitored using targeted lipid mediator lipidomics to assess potential systemic impact of BLXA4.
The frequency of TEAEs was similar in BLXA4 and placebo-treated groups with no study-related SAEs. Once-daily rinsing with BLXA4 for 28-days resulted in a greater decrease in gingival inflammation compared to placebo rinse and no-rinse control groups (mean change: 0.26 GI unit 0.21 and 0.17, respectively). PD reduction was also greater with BLXA4 oral rinse compared to placebo and no-rinse groups (mean reduction: 1.23 mm . 0.71 mm and 0.46 mm, respectively). Topical application of BLXA4 increased serum levels of SPMs.
Treatment with BLXA4 reduces local inflammation, and increases abundance of pro-resolution molecules systemically, which may dampen inflammation that can mediate progression and course of inflammatory diseases beyond periodontitis.
ClinicalTrials.gov, identifier (NCT02342691).
牙周病是全球第六大常见炎症性疾病，其发生并发症的风险很高，包括糖尿病、心血管疾病和阿尔茨海默病等炎症性疾病。炎症通路的主动缓解失败与牙周病的发病机制有关，包括牙龈炎。脂氧素 A4（LXA4）是专门的促解决脂质介质（SPM）的成员之一，可驱动炎症的解决 GPC-受体介导的途径，在牙周炎的临床前模型中具有治疗优势。
我们进行了一项随机、安慰剂对照、平行组的 1 期临床试验，以确定含有 LXA4 类似物的口腔冲洗液在牙龈炎症患者中的安全性和初步疗效。127 名个体被随机分为每日使用含 LXA4 模拟物、甲酯-苯脂氧素 A4（BLXA4）的口腔冲洗液、安慰剂冲洗液或不冲洗对照组，共 28 天。治疗中出现的不良事件（TEAEs）用于评估安全性，这是主要结局。次要结局包括牙龈炎症水平和牙周袋深度（PD）的变化。使用靶向脂质介质脂质组学监测血清 SPMs，以评估 BLXA4 的潜在全身影响。
BLXA4 和安慰剂治疗组的 TEAEs 频率相似，无研究相关的严重不良事件。与安慰剂冲洗液和不冲洗对照组相比，28 天每日冲洗 BLXA4 可使牙龈炎症明显减轻（平均变化：0.26 GI 单位 0.21 和 0.17）。与安慰剂和不冲洗组相比，BLXA4 口腔冲洗液也可使 PD 明显减少（平均减少：1.23 毫米. 0.71 毫米和 0.46 毫米）。BLXA4 的局部应用增加了血清 SPMs 的水平。
BLXA4 的治疗可减轻局部炎症，并增加系统中促解决分子的丰度，这可能会抑制炎症，从而减轻炎症性疾病的进展和病程，不仅仅是牙周炎。
ClinicalTrials.gov，标识符（NCT02342691）。
