Noradrenergic Add-on Therapy with Extended-Release Guanfacine in Alzheimer's Disease (NorAD): study protocol for a randomised clinical trial and COVID-19 amendments.
Noradrenergic Add-on Therapy with Extended-Release Guanfacine in Alzheimer's Disease (NorAD): study protocol for a randomised clinical trial and COVID-19 amendments.
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胍法辛是一种α2A肾上腺素受体激动剂，被批准用于治疗注意缺陷多动障碍（ADHD）。它被认为通过前额皮质的突触后受体起作用，调节包括注意力调节在内的执行功能。注意力在阿尔茨海默病（AD）早期受到影响，这可能与蓝斑的病理改变有关，蓝斑是大脑内去肾上腺素能通路的主要来源。考虑到阿尔茨海默病中也涉及注意力的胆碱能通路被破坏，去甲肾上腺素能和胆碱能联合治疗可能对症状性阿尔茨海默病有协同作用。NorAD试验的主要目的是评估轻度至中度阿尔茨海默病患者接受缓释胍法辛（GXR）与安慰剂联合治疗12周后认知能力的变化。NorAD是一项为期3个月，单中心，随机，双盲，安慰剂对照的缓释胍法辛（GXR） III期试验，用于轻度至中度阿尔茨海默病患者。总共160名参与者将被随机分配，接受每日胍法辛或安慰剂联合批准的胆碱酯酶治疗12周。与安慰剂组相比，治疗组的主要结局是认知的变化，通过阿尔茨海默病评估量表-认知亚量表（ADAS-Cog）来测量，从基线到随访。次要结果包括额外的注意力认知测量的变化（注意力测试：轨迹A和B，数字符号替代，日常注意力测试和CANTAB-RVP），神经精神症状（神经精神量表），照顾者负担（Zarit负担访谈）和日常生活活动（阿尔茨海默病合作研究-日常生活活动量表）。从2020年7月起，还将评估停止治疗后观察到的变化。有强有力的证据表明阿尔茨海默病早期去甲肾上腺素能功能障碍。NorAD试验旨在确定除标准胆碱能治疗外，胍法辛（一种去甲肾上腺素能α -2激动剂）是否能改善注意力和认知能力。ClinicalTrials.govNCT03116126。注册于2017年4月14日草案：2016-002598-36
Guanfacine is a α2A adrenergic receptor agonist approved for treating attention deficit hyperactivity disorder (ADHD). It is thought to act via postsynaptic receptors in the prefrontal cortex, modulating executive functions including the regulation of attention. Attention is affected early in Alzheimer’s disease (AD), and this may relate to pathological changes within the locus coeruleus, the main source of noradrenergic pathways within the brain. Given that cholinergic pathways, also involved in attention, are disrupted in AD, the combination of noradrenergic and cholinergic treatments may have a synergistic effect on symptomatic AD. The primary objective of the NorAD trial is to evaluate the change in cognition with 12 weeks of treatment of extended-release guanfacine (GXR) against a placebo as a combination therapy with cholinesterase inhibitors in participants with mild to moderate Alzheimer’s disease. NorAD is a 3-month, single-centre, randomised, double-blind, placebo-controlled, phase III trial of extended-release guanfacine (GXR) in participants with mild to moderate Alzheimer’s disease. A total of 160 participants will be randomised to receive either daily guanfacine or placebo in combination with approved cholinesterase treatment for 12 weeks. The primary outcome is the change in cognition, as measured by the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), from baseline to follow-up in the treatment group compared to the placebo group. Secondary outcomes include the change in additional cognitive measures of attention (Tests of Attention: Trails A and B, digit-symbol substitution, Test of Everyday Attention and CANTAB-RVP), neuropsychiatric symptoms (Neuropsychiatric Inventory), caregiver burden (Zarit Burden Interview) and activities of daily living (Alzheimer’s Disease Co-operative Study – Activities of Daily Living Inventory). From July 2020, observation of change following cessation of treatment is also being assessed. There is strong evidence for early noradrenergic dysfunction in Alzheimer’s disease. The NorAD trial aims to determine whether guanfacine, a noradrenergic alpha-2 agonist, improves attention and cognition when used in addition to standard cholinergic treatment. ClinicalTrials.govNCT03116126. Registered on 14 April 2017 EudraCT: 2016-002598-36
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影响因子：
11
作者：
Dalmaijer, Edwin S.;Li, Korina M. S.;Malhotra, Paresh A.
通讯作者：
Malhotra, Paresh A.
DOI：
10.1097/00002093-198701040-00005
发表时间：
1987-01-01
影响因子：
2.1
作者：
Bondareff, W;Mountjoy, C Q;Hauser, D L
通讯作者：
Hauser, D L
DOI：
10.3233/jad-180688
发表时间：
2018
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Ehrenberg AJ;Suemoto CK;França Resende EP;Petersen C;Leite REP;Rodriguez RD;Ferretti-Rebustini REL;You M;Oh J;Nitrini R;Pasqualucci CA;Jacob-Filho W;Kramer JH;Gatchel JR;Grinberg LT
通讯作者：
Grinberg LT
DOI：
10.1159/000106731
发表时间：
1994-09-01
期刊：
DEMENTIA
影响因子：
--
作者：
BIERER, LM;AISEN, PS;DAVIS, KL
通讯作者：
DAVIS, KL
影响因子：
11.2
作者：
Malhotra, PA;Parton, AD;Husain, M
通讯作者：
Husain, M