Abstract：
BACKGROUND: Melatonin is an antioxidant and anti-inflammatory agent that modulates the immune system by scavenging free radicals, reducing the upregulation of pro-inflammatory cytokines, and reducing transendothelial cell migration. Therefore, melatonin may play a role in regulating multiple sclerosis (MS) disease activity. However, little is known about how melatonin supplementation effects individuals with MS.
OBJECTIVE: Determine if there was a dose-dependent elevation in urine and serum melatonin concentrations. Determine if melatonin supplementation had an impact on patient reported outcomes.
METHODS: This was a randomized, dose-blinded exploratory study. Adults (age 18-65) with relapsing forms of multiple sclerosis (RMS) treated with a stable dose of oral disease modifying therapy for at least 6 months were randomized into melatonin 3 mg or 5 mg daily. Urinary and serum melatonin levels and modified fatigue impact scale (MFIS), multiple sclerosis impact scale (MSIS-29), and Pittsburgh sleep quality index (PSQI), patient determined disease steps (PDDS) and performance scales (PS) were measured at baseline, 3, 6, and 12 months. Urinary and serum melatonin analyses was performed to estimate mean concentrations and their differences between treatment arms over time by a repeated measures linear mixed model. The model included treatment, assessment time, and treatment × time interaction.
RESULTS: Thirty patients, randomized 1:1, were analyzed in an intent to treat population. Twenty-three completed the study. The repeated measures linear mixed model analysis of all timepoints revealed higher melatonin concentrations in patients on 5 mg compared to 3 mg melatonin for both urinary 6-SMT (p = 0.03) and serum melatonin (p = 0.04). MFIS, MSIS-29, PSQI, and PDSS-PS scores did not significantly change from baseline to month 12. No significant differences in these measures were seen between the two doses. Five patients stopped melatonin (three on 5 mg and two on 3 mg) due to adverse events, including one patient who developed focal spongiotic dermatitis. One patient experienced three consecutive serious adverse events that were unrelated to melatonin supplementation.
CONCLUSIONS: The 5 mg melatonin supplementation group had higher concentrations of urinary 6-SMT and serum melatonin compared to the 3 mg group over 12 months of treatment. There was a correlation between 6-SMT and serum melatonin concentrations. This suggests that measuring serum melatonin is a reliable alternative to measuring urinary 6-SMT. However, no differences in clinical benefit between the two dosage groups were demonstrated in the patient reported outcomes.
BACKGROUND: NCT03498131.
OBJECTIVE: Determine if there was a dose-dependent elevation in urine and serum melatonin concentrations. Determine if melatonin supplementation had an impact on patient reported outcomes.
METHODS: This was a randomized, dose-blinded exploratory study. Adults (age 18-65) with relapsing forms of multiple sclerosis (RMS) treated with a stable dose of oral disease modifying therapy for at least 6 months were randomized into melatonin 3 mg or 5 mg daily. Urinary and serum melatonin levels and modified fatigue impact scale (MFIS), multiple sclerosis impact scale (MSIS-29), and Pittsburgh sleep quality index (PSQI), patient determined disease steps (PDDS) and performance scales (PS) were measured at baseline, 3, 6, and 12 months. Urinary and serum melatonin analyses was performed to estimate mean concentrations and their differences between treatment arms over time by a repeated measures linear mixed model. The model included treatment, assessment time, and treatment × time interaction.
RESULTS: Thirty patients, randomized 1:1, were analyzed in an intent to treat population. Twenty-three completed the study. The repeated measures linear mixed model analysis of all timepoints revealed higher melatonin concentrations in patients on 5 mg compared to 3 mg melatonin for both urinary 6-SMT (p = 0.03) and serum melatonin (p = 0.04). MFIS, MSIS-29, PSQI, and PDSS-PS scores did not significantly change from baseline to month 12. No significant differences in these measures were seen between the two doses. Five patients stopped melatonin (three on 5 mg and two on 3 mg) due to adverse events, including one patient who developed focal spongiotic dermatitis. One patient experienced three consecutive serious adverse events that were unrelated to melatonin supplementation.
CONCLUSIONS: The 5 mg melatonin supplementation group had higher concentrations of urinary 6-SMT and serum melatonin compared to the 3 mg group over 12 months of treatment. There was a correlation between 6-SMT and serum melatonin concentrations. This suggests that measuring serum melatonin is a reliable alternative to measuring urinary 6-SMT. However, no differences in clinical benefit between the two dosage groups were demonstrated in the patient reported outcomes.
BACKGROUND: NCT03498131.
摘要：
背景：褪黑素是一种抗氧化剂和抗炎剂，通过清除自由基来调节免疫系统，减少促炎细胞因子的上调，减少内皮细胞迁移。因此,褪黑素可能在调节多发性硬化症（MS）疾病活动中起作用。然而,关于补充褪黑激素如何影响MS患者的情况知之甚少。
目的：确定尿液和血清褪黑素浓度是否存在剂量依赖性升高。确定是否补充褪黑激素对患者报告的结果有影响。
方法：这是一个随机的，剂量盲探索性研究。使用稳定剂量的口腔疾病改善疗法治疗至少6个月的复发性多发性硬化症（RMS）的成年人（18-65岁）随机分为每天3mg或5mg的褪黑激素。尿和血清褪黑激素水平和改良疲劳影响量表（MFIS），多发性硬化症影响量表（MSIS-29），匹兹堡睡眠质量指数(PSQI)在基线测量患者确定的疾病步骤（PDDS）和表现量表（PS），3、6和12个月。进行尿和血清褪黑素分析以通过重复测量线性混合模型来估计平均浓度及其随时间在治疗组之间的差异。该模型包括治疗，评估时间,和治疗×时间相互作用。
结果：30名患者，随机1:1，在治疗人群的意图中进行了分析。23人完成了这项研究。所有时间点的重复测量线性混合模型分析显示，对于尿6-SMT（p=0.03）和血清褪黑激素（p=0.04），5mg患者的褪黑激素浓度高于3mg褪黑激素。MFIS,MSIS-29,PSQI,PDSS-PS评分从基线到第12个月无显著变化.在两个剂量之间没有看到这些测量的显著差异。5例患者因不良事件停用褪黑素（3例服用5mg，2例服用3mg），包括一名发生局灶性海绵状皮炎的患者。一名患者经历了三次与补充褪黑激素无关的连续严重不良事件。
结论：在治疗12个月期间，与3mg组相比，5mg褪黑素补充组的尿6-SMT和血清褪黑素浓度更高。6-SMT与血清褪黑素浓度之间存在相关性。这表明测量血清褪黑素是测量尿6-SMT的可靠替代方法。然而,在患者报告的结局中,两个剂量组之间的临床获益没有差异.
背景：NCT03498131。
目的：确定尿液和血清褪黑素浓度是否存在剂量依赖性升高。确定是否补充褪黑激素对患者报告的结果有影响。
方法：这是一个随机的，剂量盲探索性研究。使用稳定剂量的口腔疾病改善疗法治疗至少6个月的复发性多发性硬化症（RMS）的成年人（18-65岁）随机分为每天3mg或5mg的褪黑激素。尿和血清褪黑激素水平和改良疲劳影响量表（MFIS），多发性硬化症影响量表（MSIS-29），匹兹堡睡眠质量指数(PSQI)在基线测量患者确定的疾病步骤（PDDS）和表现量表（PS），3、6和12个月。进行尿和血清褪黑素分析以通过重复测量线性混合模型来估计平均浓度及其随时间在治疗组之间的差异。该模型包括治疗，评估时间,和治疗×时间相互作用。
结果：30名患者，随机1:1，在治疗人群的意图中进行了分析。23人完成了这项研究。所有时间点的重复测量线性混合模型分析显示，对于尿6-SMT（p=0.03）和血清褪黑激素（p=0.04），5mg患者的褪黑激素浓度高于3mg褪黑激素。MFIS,MSIS-29,PSQI,PDSS-PS评分从基线到第12个月无显著变化.在两个剂量之间没有看到这些测量的显著差异。5例患者因不良事件停用褪黑素（3例服用5mg，2例服用3mg），包括一名发生局灶性海绵状皮炎的患者。一名患者经历了三次与补充褪黑激素无关的连续严重不良事件。
结论：在治疗12个月期间，与3mg组相比，5mg褪黑素补充组的尿6-SMT和血清褪黑素浓度更高。6-SMT与血清褪黑素浓度之间存在相关性。这表明测量血清褪黑素是测量尿6-SMT的可靠替代方法。然而,在患者报告的结局中,两个剂量组之间的临床获益没有差异.
背景：NCT03498131。
