Study protocol for LOMCAD Trial: Effect of lomerizine hydrochloride to prevent recurrence of cerebral ischemic events in CADASIL patients

Abstract

Objectives: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is one of the most common monogenic cerebral small vessel diseases. Our previous observational study suggested that lomerizine hydrochloride, a calcium channel blocker approved in Japan in 1999 for the prevention of migraine headaches, is also effective for preventing recurrent ischemic stroke in CADASIL patients. The aim of this study (LOMCAD trial) is to verify the efficacy of lomerizine hydrochloride.

Materials and methods: This is a multicenter, prospective, single-arm trial, using a historical control for comparison. CADASIL patients with a history of two or more cerebral ischemic events within the last two years will be administered lomerizine hydrochloride (5-mg tablet twice daily) for 24 months. The primary endpoint is symptomatic cerebral ischemic events during the 24-month period. Using our historical data and Bayesian sample size calculation based on a prior predictive distribution, the planned sample size was determined as 20 subjects.

Conclusion: We have planned a clinical trial to verify the effectiveness of lomerizine hydrochloride as prophylaxis to prevent recurrent cerebral ischemic events in CADASIL patients.

Registration: The LOMCAD trial has been registered in the Japan Registry of Clinical Trials (jRCTs051220072, https://jrct.niph.go.jp/latest-detail/jRCTs051220072).

Keywords: Bayesian method; CADASIL; Cerebral ischemic events; Historical control; Lomerizine hydrochloride; Protocol; Single-arm.