Abstract：
BACKGROUND: Migraine is a common and distressing neurological condition characterised by recurrent throbbing headaches, nausea and heightened sensitivity to light and sound. Accumulating evidence suggests that cerebral arteries dilate during migraine, causing distal microvessels to constrict, which could activate nociceptors and cause onset of headache pain. If so, preventing or attenuating chronic microvascular constriction, and promoting a dilatory phenotype, may reduce frequency and/or severity of migraines. The primary aim of the L-Arginine and Aged Garlic Extract (LARGE) trial is to investigate whether oral treatment with dietary nutraceuticals, L-arginine and aged garlic extract (AGE), both systemic vasodilatory agents, will alleviate migraine frequency, duration and severity in adults with chronic frequent episodic migraines.
METHODS: The study is a randomised double-blind placebo-controlled phase-II single-site clinical trial conducted in Perth, Australia. The target sample is to recruit 240 participants diagnosed with chronic frequent episodic migraines between 18 and 80 years of age. Participants will be randomised to one of four treatment groups for 14 weeks (placebo induction for 2 weeks, followed by 12 weeks on one of the respective treatment arms): placebo, L-arginine, AGE, or a combination of L-arginine and AGE. The doses of L-arginine and AGE are 1.5 g and 1 g daily, respectively. The primary outcome is to assess migraine response using change in migraine frequency and intensity between baseline and 12 weeks. Secondary outcomes include the impact of L-arginine and/or AGE on photosensitivity, retinal vessel changes, and blood biomarker concentrations of vascular tone, following a 12-week intervention.
CONCLUSIONS: The protocol describes the oral administration of 2 nutraceutical-based interventions as possible prophylactic treatments for chronic frequent episodic migraines, with potential for direct clinical translation of outcomes. Potential limitations of the study include the fixed-dose design of each treatment arm and that in vivo neuroimaging methods, such as magnetic resonance imaging (MRI), will not be conducted to determine putative cerebro-vasodilatory changes to coincide with the outcome measures. Dose-response studies may be indicated.
BACKGROUND: The trial was retrospectively registered with the Australian New Zealand Clinical Trials Registry ACTRN12621001476820 (Universal Trial Number: U1111-1268-1117) on 04/08/2021. This is protocol version 1, submitted on 25/11/2022.
METHODS: The study is a randomised double-blind placebo-controlled phase-II single-site clinical trial conducted in Perth, Australia. The target sample is to recruit 240 participants diagnosed with chronic frequent episodic migraines between 18 and 80 years of age. Participants will be randomised to one of four treatment groups for 14 weeks (placebo induction for 2 weeks, followed by 12 weeks on one of the respective treatment arms): placebo, L-arginine, AGE, or a combination of L-arginine and AGE. The doses of L-arginine and AGE are 1.5 g and 1 g daily, respectively. The primary outcome is to assess migraine response using change in migraine frequency and intensity between baseline and 12 weeks. Secondary outcomes include the impact of L-arginine and/or AGE on photosensitivity, retinal vessel changes, and blood biomarker concentrations of vascular tone, following a 12-week intervention.
CONCLUSIONS: The protocol describes the oral administration of 2 nutraceutical-based interventions as possible prophylactic treatments for chronic frequent episodic migraines, with potential for direct clinical translation of outcomes. Potential limitations of the study include the fixed-dose design of each treatment arm and that in vivo neuroimaging methods, such as magnetic resonance imaging (MRI), will not be conducted to determine putative cerebro-vasodilatory changes to coincide with the outcome measures. Dose-response studies may be indicated.
BACKGROUND: The trial was retrospectively registered with the Australian New Zealand Clinical Trials Registry ACTRN12621001476820 (Universal Trial Number: U1111-1268-1117) on 04/08/2021. This is protocol version 1, submitted on 25/11/2022.
摘要：
背景：偏头痛是一种常见且令人痛苦的神经系统疾病，其特征是反复搏动性头痛，恶心，对光和声音敏感。越来越多的证据表明偏头痛时脑动脉扩张，导致远端微血管收缩，这可能会激活伤害感受器并引起头痛。如果是,预防或减轻慢性微血管收缩，促进扩张表型，可以降低偏头痛的频率和/或严重程度。L-精氨酸和老年大蒜提取物（LARGE）试验的主要目的是调查是否口服膳食营养品，L-精氨酸和陈年大蒜提取物（AGE），两者都是全身性血管扩张剂,会缓解偏头痛的频率，成人慢性频繁发作性偏头痛的持续时间和严重程度。
方法：该研究是一项在珀斯进行的随机双盲安慰剂对照II期单中心临床试验，澳大利亚。目标样本是招募240名被诊断患有18至80岁的慢性频繁发作性偏头痛的参与者。参与者将被随机分为四个治疗组之一，持续14周（安慰剂诱导2周，随后在各自的治疗组之一上进行12周）：安慰剂，L-精氨酸,年龄,或L-精氨酸和AGE的组合。L-精氨酸和AGE的剂量为每天1.5g和1g，分别。主要结果是使用基线和12周之间的偏头痛频率和强度的变化来评估偏头痛反应。次要结果包括L-精氨酸和/或AGE对光敏性的影响，视网膜血管变化,和血管张力的血液生物标志物浓度，经过12周的干预。
结论：该方案描述了口服2种基于营养药物的干预措施，作为慢性频繁发作性偏头痛的可能预防性治疗，具有直接临床转译结果的潜力。该研究的潜在局限性包括每个治疗臂的固定剂量设计以及体内神经成像方法，如磁共振成像（MRI），将不进行确定推定的脑血管舒张变化以与结果指标一致。可能需要进行剂量反应研究。
背景：该试验于2021年4月8日在澳大利亚新西兰临床试验注册中心ACTRN12621001476820（通用试验编号：U1111-1268-1117）进行回顾性注册。这是协议版本1，于2022年11月25日提交。
方法：该研究是一项在珀斯进行的随机双盲安慰剂对照II期单中心临床试验，澳大利亚。目标样本是招募240名被诊断患有18至80岁的慢性频繁发作性偏头痛的参与者。参与者将被随机分为四个治疗组之一，持续14周（安慰剂诱导2周，随后在各自的治疗组之一上进行12周）：安慰剂，L-精氨酸,年龄,或L-精氨酸和AGE的组合。L-精氨酸和AGE的剂量为每天1.5g和1g，分别。主要结果是使用基线和12周之间的偏头痛频率和强度的变化来评估偏头痛反应。次要结果包括L-精氨酸和/或AGE对光敏性的影响，视网膜血管变化,和血管张力的血液生物标志物浓度，经过12周的干预。
结论：该方案描述了口服2种基于营养药物的干预措施，作为慢性频繁发作性偏头痛的可能预防性治疗，具有直接临床转译结果的潜力。该研究的潜在局限性包括每个治疗臂的固定剂量设计以及体内神经成像方法，如磁共振成像（MRI），将不进行确定推定的脑血管舒张变化以与结果指标一致。可能需要进行剂量反应研究。
背景：该试验于2021年4月8日在澳大利亚新西兰临床试验注册中心ACTRN12621001476820（通用试验编号：U1111-1268-1117）进行回顾性注册。这是协议版本1，于2022年11月25日提交。
