Department of Neuroinflammation, UCL Institute of Neurology, London, United Kingdom.
PLoS One. 2013 Aug 1;8(8):e70019. doi: 10.1371/journal.pone.0070019. Print 2013.
Lamotrigine trial in SPMS was a randomised control trial to assess whether partial blockade of sodium channels has a neuroprotective effect. The current study was an additional study to investigate the value of neurofilament (NfH) and other biomarkers in predicting prognosis and/or response to treatment.
SPMS patients who attended the NHNN or the Royal Free Hospital, UK, eligible for inclusion were invited to participate in the biomarker study. Primary outcome was whether lamotrigine would significantly reduce detectable serum NfH at 0-12, 12-24 and 0-24 months compared to placebo. Other serum/plasma and CSF biomarkers were also explored.
Treatment effect by comparing absolute changes in NfH between the lamotrigine and placebo group showed no difference, however based on serum lamotrigine adherence there was significant decline in NfH (NfH 12-24 months p=0.043, Nfh 0-24 months p=0.023). Serum NfH correlated with disability: walking times, 9-HPT (non-dominant hand), PASAT, z-score, MSIS-29 (psychological) and EDSS and MRI cerebral atrophy and MTR. Other biomarkers explored in this study were not found to be significantly associated, aside from that of plasma osteopontin.
The relations between NfH and clinical scores of disability and MRI measures of atrophy and disease burden support NfH being a potential surrogate endpoint complementing MRI in neuroprotective trials and sample sizes for such trials are presented here. We did not observe a reduction in NfH levels between the Lamotrigine and placebo arms, however, the reduction in serum NfH levels based on lamotrigine adherence points to a possible neuroprotective effect of lamotrigine on axonal degeneration.
SPMS 中的拉莫三嗪试验是一项随机对照试验，旨在评估钠离子通道的部分阻断是否具有神经保护作用。本研究是一项额外的研究，旨在探讨神经丝（NfH）和其他生物标志物在预测预后和/或治疗反应中的价值。
邀请参加 NHNN 或英国皇家自由医院的 SPMS 患者参加生物标志物研究，这些患者符合纳入标准。主要结果是与安慰剂相比，拉莫三嗪是否会显著降低 0-12、12-24 和 0-24 个月时可检测的血清 NfH。还探讨了其他血清/血浆和 CSF 生物标志物。
通过比较拉莫三嗪组和安慰剂组之间 NfH 的绝对变化，治疗效果没有差异，但是基于血清拉莫三嗪依从性，NfH 明显下降（NfH 12-24 个月 p=0.043，Nfh 0-24 个月 p=0.023）。血清 NfH 与残疾相关：行走时间、9-HPT（非优势手）、PASAT、z 评分、MSIS-29（心理）和 EDSS 以及大脑萎缩和 MTR 的 MRI。除了血浆骨桥蛋白外，本研究中探索的其他生物标志物未发现与疾病显著相关。
NfH 与残疾的临床评分和 MRI 测量的萎缩和疾病负担之间的关系支持 NfH 作为补充 MRI 的神经保护试验的潜在替代终点，并提出了此类试验的样本量。我们没有观察到拉莫三嗪组和安慰剂组之间 NfH 水平的降低，但是，基于拉莫三嗪依从性的血清 NfH 水平降低表明拉莫三嗪对轴突变性可能具有神经保护作用。
