背景:慢性腹痛是慢性胰腺炎(CP)的标志性症状,50%至80%的患者寻求医疗护理以控制疼痛。虽然有几个管理选项可用,结果往往令人失望,阿片类药物仍然是治疗的支柱。阿片类药物诱导的痛觉过敏是一种导致剂量递增的现象,这可能部分是由于阿片类药物对与疼痛相关的电压门控钠通道的影响。临床前观察表明,阿片类药物和抗癫痫药物拉科酰胺的组合可减少阿片类药物诱导的痛觉过敏并改善疼痛控制。
目的:在这项1期试验中,我们的目标是确定安全性,耐受性,以及在阿片类药物中加入拉考沙胺治疗疼痛性CP的剂量限制性毒性,并评估在CP患者中加入拉考沙胺治疗的初步研究的可行性。作为一个探索的目标,我们将评估在疼痛性CP患者的阿片类药物治疗中加入拉科沙胺的疗效.
方法:使用贝叶斯最优区间设计,我们将进行一项剂量递增试验,在纳入3号队列的CP疼痛患者中,在阿片类药物治疗中加入拉考沙胺.初始剂量为50毫克,每天口服两次,随后递增至最大剂量400毫克/天,在每个剂量水平下给予拉科沙胺7天。不良事件将根据不良事件通用术语标准(5.0版)进行记录。
结果:截至2023年12月,我们目前已注册6名参与者。参加的人数最少为12人,最多24人。我们预计将于2025年3月公布结果。
结论:该试验将测试研究设计的可行性,并为阿片类药物治疗疼痛性CP的耐受性和安全性提供保证。预计拉科沙胺将被证明是安全和良好的耐受性,支持随后的2期试验,评估拉科沙胺+阿片类药物治疗对疼痛性CP患者的疗效,拉科沙胺与阿片类药物联合使用将降低缓解疼痛所需的阿片类药物剂量,并改善阿片类药物治疗疼痛性CP的安全性。
背景:Clinicaltrials.govNCT05603702;https://clinicaltrials.gov/study/NCT05603702。
■PRR1-10.2196/50513。
BACKGROUND: Chronic abdominal pain is the hallmark symptom of chronic pancreatitis (CP), with 50% to 80% of patients seeking medical attention for pain control. Although several management options are available, outcomes are often disappointing, and opioids remain a mainstay of therapy. Opioid-induced hyperalgesia is a phenomenon resulting in dose escalation, which may occur partly because of the effects of opioids on voltage-gated sodium channels associated with pain. Preclinical observations demonstrate that the combination of an opioid and the antiseizure drug lacosamide diminishes opioid-induced hyperalgesia and improves pain control.
OBJECTIVE: In this phase 1 trial, we aim to determine the safety, tolerability, and dose-limiting toxicity of adding lacosamide to opioids for the treatment of painful CP and assess the feasibility of performance of a pilot study of adding lacosamide to opioid therapy in patients with CP. As an exploratory aim, we will assess the efficacy of adding lacosamide to opioid therapy in patients with painful CP.
METHODS: Using the Bayesian optimal interval design, we will conduct a dose-escalation trial of adding lacosamide to opioid therapy in patients with painful CP enrolled in cohorts of size 3. The initial dose will be 50 mg taken orally twice a day, followed by incremental increases to a maximum dose of 400 mg/day, with lacosamide administered for 7 days at each dose level. Adverse events will be documented according to Common Terminology Criteria for Adverse Events (version 5.0).
RESULTS: As of December 2023, we have currently enrolled 6 participants. The minimum number of participants to be enrolled is 12 with a maximum of 24. We expect to publish the results by March 2025.
CONCLUSIONS: This trial will test the feasibility of the study design and provide reassurance regarding the tolerability and safety of opioids in treating painful CP. It is anticipated that lacosamide will prove to be safe and well tolerated, supporting a subsequent phase 2 trial assessing the efficacy of lacosamide+opioid therapy in patients with painful CP, and that lacosamide combined with opiates will lower the opioid dose necessary for pain relief and improve the safety profile of opioid use in treating painful CP.
BACKGROUND: Clinicaltrials.gov NCT05603702; https://clinicaltrials.gov/study/NCT05603702.
UNASSIGNED: PRR1-10.2196/50513.