Oral curcumin for Alzheimer's disease: tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study.
Oral curcumin for Alzheimer's disease: tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study.
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DOI：
10.1186/alzrt146
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Cole GM
中科院分区：
文献类型：
--
作者：
Ringman JM;Frautschy SA;Teng E;Begum AN;Bardens J;Beigi M;Gylys KH;Badmaev V;Heath DD;Apostolova LG;Porter V;Vanek Z;Marshall GA;Hellemann G;Sugar C;Masterman DL;Montine TJ;Cummings JL;Cole GM
姜黄素是一种从姜黄龙林植物中提取的多酚类化合物，已被证明具有抗氧化和抗炎作用，以及减少β -淀粉样蛋白聚集的作用。它减少了阿尔茨海默病（AD）转基因模型的病理，是治疗人类AD的有希望的候选药物。本研究的目的是产生AD患者姜黄素的耐受性和初步临床和生物标志物疗效数据。我们对Curcumin C3 Complex®进行了一项为期24周的随机、双盲、安慰剂对照研究，开放标签延长至48周。36名轻度至中度AD患者随机接受安慰剂、2克/天或4克/天口服姜黄素，持续24周。从第24周到第48周，接受姜黄素治疗的受试者继续服用相同剂量的姜黄素，而之前接受安慰剂治疗的受试者按1:1的比例随机分为2克/天或4克/天。主要结果测量是不良事件的发生率，临床实验室检查的变化和阿尔茨海默病评估量表-认知亚量表（ADAS-Cog）在完成研究的24周时。次要结果测量包括神经精神量表（NPI）、阿尔茨海默病合作研究-日常生活活动量表（ADCS-ADL）、血浆中Aβ1-40和Aβ1-42水平以及脑脊液中Aβ1-42、t-tau、p-tau181和f2 -异前列腺素水平。姜黄素及其代谢物在给药后4小时内的血浆水平也被测量。完成者（n = 30）的平均年龄为73.5岁，平均迷你精神状态检查（MMSE）得分为22.5分。安慰剂组有1名受试者退出（8%，记忆力恶化），姜黄素组有5/24名受试者退出（21%，3名因胃肠道症状）。姜黄素C3复合物®与血细胞比容降低和血糖水平升高相关，但临床不显著。在临床或生物标志物疗效测量方面，治疗组之间没有差异。血浆中测量的天然姜黄素水平较低（7.32 ng/mL）。姜黄素总体耐受良好，但有3名受试者因胃肠道症状而停药。在这项为期24周的安慰剂对照试验中，我们无法证明姜黄素C3复合物®治疗AD的临床或生化证据，尽管初步数据表明该化合物的生物利用度有限。ClinicalTrials.gov标识符：NCT00099710。
Curcumin is a polyphenolic compound derived from the plant Curcuma Long Lin that has been demonstrated to have antioxidant and anti-inflammatory effects as well as effects on reducing beta-amyloid aggregation. It reduces pathology in transgenic models of Alzheimer's disease (AD) and is a promising candidate for treating human AD. The purpose of the current study is to generate tolerability and preliminary clinical and biomarker efficacy data on curcumin in persons with AD. We performed a 24-week randomized, double blind, placebo-controlled study of Curcumin C3 Complex® with an open-label extension to 48 weeks. Thirty-six persons with mild-to-moderate AD were randomized to receive placebo, 2 grams/day, or 4 grams/day of oral curcumin for 24 weeks. For weeks 24 through 48, subjects that were receiving curcumin continued with the same dose, while subjects previously receiving placebo were randomized in a 1:1 ratio to 2 grams/day or 4 grams/day. The primary outcome measures were incidence of adverse events, changes in clinical laboratory tests and the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) at 24 weeks in those completing the study. Secondary outcome measures included the Neuropsychiatric Inventory (NPI), the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) scale, levels of Aβ1-40 and Aβ1-42 in plasma and levels of Aβ1-42, t-tau, p-tau181 and F2-isoprostanes in cerebrospinal fluid. Plasma levels of curcumin and its metabolites up to four hours after drug administration were also measured. Mean age of completers (n = 30) was 73.5 years and mean Mini-Mental Status Examination (MMSE) score was 22.5. One subject withdrew in the placebo (8%, worsened memory) and 5/24 subjects withdrew in the curcumin group (21%, 3 due to gastrointestinal symptoms). Curcumin C3 Complex® was associated with lowered hematocrit and increased glucose levels that were clinically insignificant. There were no differences between treatment groups in clinical or biomarker efficacy measures. The levels of native curcumin measured in plasma were low (7.32 ng/mL). Curcumin was generally well-tolerated although three subjects on curcumin withdrew due to gastrointestinal symptoms. We were unable to demonstrate clinical or biochemical evidence of efficacy of Curcumin C3 Complex® in AD in this 24-week placebo-controlled trial although preliminary data suggest limited bioavailability of this compound. ClinicalTrials.gov Identifier: NCT00099710.
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影响因子：
4.2
作者：
Frautschy, SA;Hu, W;Cole, GM
通讯作者：
Cole, GM
DOI：
10.1016/s1570-0232(02)00714-6
发表时间：
2003-01-05
影响因子：
3
作者：
Heath, DD;Pruitt, MA;Rock, CL
通讯作者：
Rock, CL
DOI：
10.1124/jpet.108.137455
发表时间：
2008-07-01
影响因子：
3.5
作者：
Begum, Aynun N.;Jones, Mychica R.;Frautschy, Sally A.
通讯作者：
Frautschy, Sally A.
影响因子：
9.9
作者：
MCKHANN, G;DRACHMAN, D;STADLAN, EM
通讯作者：
STADLAN, EM
影响因子：
5.3
作者：
Lim, GP;Chu, T;Cole, GM
通讯作者：
Cole, GM