ArticleTrials2022
Noradrenergic Add-on Therapy with Extended-Release Guanfacine in Alzheimer's Disease (NorAD): study protocol for a randomised clinical trial and COVID-19 amendments.
Article in Trials, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03116126 (Randomised Clinical Trial of Noradrenergic Add-on Therapy With Extended-Release Guanfacine in Alzheimer's Disease), which is not on this map. Cited by 13 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Randomised Clinical Trial of Noradrenergic Add-on Therapy With Extended-Release Guanfacine in Alzheimer's Disease
Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Digital Cognitive Phenotyping for Differential Diagnosis and Monitoring in Neurological Conditions.Annals of clinical and translational neurology · 2026Article
- Cortical synchrony is reduced in Alzheimer's disease and relates to arousal state.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Alzheimer Combination Therapies: Overview and Scenarios.The journal of prevention of Alzheimer's disease · 2025Review
- Catecholaminergic nucleus integrity and Alzheimer's pathology, symptoms, and progression.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Biomarker evidence of neurodegeneration in mid-life former rugby players.Brain : a journal of neurology · 2025Article
- Pupil-linked arousal, cortical activity, and cognition in Alzheimer's disease.Brain communications · 2025Article
- Noradrenergic therapies in neurodegenerative disease: from symptomatic to disease modifying therapy?Brain communications · 2025Review
- Successful treatment with guanfacine in a long-COVID case manifesting marked cognitive impairment.Neuropsychopharmacology reports · 2024Article
- Scientific rationale for the use of α2A-adrenoceptor agonists in treating neuroinflammatory cognitive disorders.Molecular psychiatry · 2023Review
- The Contribution of the Locus Coeruleus-Noradrenaline System Degeneration during the Progression of Alzheimer's Disease.Biology · 2022Review
- Linking the Amyloid, Tau, and Mitochondrial Hypotheses of Alzheimer's Disease and Identifying Promising Drug Targets.Biomolecules · 2022Review
- Cognitive and neuropsychiatric effects of noradrenergic treatment in Alzheimer's disease: systematic review and meta-analysis.Journal of neurology, neurosurgery, and psychiatry · 2022Article
- New approaches for the quantification and targeting of noradrenergic dysfunction in Alzheimer's disease.Annals of clinical and translational neurology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 6 institutions in 1 country.
Funding
Abstract
backgroundGuanfacine 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. METHODS/
designNorAD 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. DISCUSSION: 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.
trial registrationClinicalTrials.gov NCT03116126 . Registered on 14 April 2017 EudraCT: 2016-002598-36.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.