Noradrenergic Add-on Therapy With Guanfacine (NorAD)

  • End date
    Dec 31, 2022
  • participants needed
  • sponsor
    Imperial College London
Updated on 15 July 2022
mini-mental state examination
alzheimer's disease
cognitive assessment


NorAD is a clinical trial funded by the UK National Institute of Health Research. In this trial the investigators will assess whether a long-acting preparation of guanfacine, a drug used to treat Attention Deficit Hyperactivity Disorder in children, can improve thinking (particularly attention) in Alzheimer's Disease when it is added to the standard NICE-approved drugs that are normally used in this condition.

This is a randomized clinical trial designed to evaluate the efficacy of extended-release guanfacine as an add-on therapy in AD, and whether it improves cognition compared to standard cholinergic therapy alone.


There is evidence suggesting that both noradrenaline and acetylcholine have key roles to play in attention. Guanfacine acts by increasing levels of noradrenaline, a substance in the brain which is closely linked with attention, both noradrenaline levels and attentional performance have been shown to be reduced in Alzheimer's Disease.

In this study the investigators propose that modulation of the noradrenergic deficit that has been described in Alzheimer's Disease in addition to standard cholinergic treatment could have significant positive effects on cognition, particularly in those patients who suffer from attentional impairments. The investigators want to assess whether long-acting guanfacine should be used in addition to NICE-approved drugs that are currently being used in AD as part of combination therapy.

It is a single-centre, randomised, parallel-group, double-blind controlled Phase 3 trial to compare the efficacy of standard cholinergic therapy (Donepezil, Rivastigmine or Galantamine) plus extended release guanfacine (2mg GXR) versus standard cholinergic therapy plus placebo on Cognition (as measured by the ADAS-Cog) in patients with mild to moderate Alzheimer's Disease.

The trial, which will recruit 160 patients (80 randomised to GXR add-on therapy and 80 randomised to placebo), based at Imperial College London - Imperial College Healthcare NHS Trust.

Condition Alzheimer Disease
Treatment Placebo, guanfacine
Clinical Study IdentifierNCT03116126
SponsorImperial College London
Last Modified on15 July 2022


Yes No Not Sure

Inclusion Criteria

NINCDS/ADRDA criteria for probable AD
MMSE at assessment = 10-30
Identified informant to accompany patient at all visits
Stable dose of donepezil, galantamine or rivastigmine for preceding 12 weeks

Exclusion Criteria

Labile blood pressure or new antihypertensive medication started within 3 weeks
Severe coronary insufficiency or myocardial infarction in previous 6 months
History of unexplained syncope within the preceding 12 months
Cardiac Conduction Block
Severe Hepatic Impairment (ALT > 120 (Upper Limit of Normal (ULN) is 40) OR Alkaline Phosphatase > 390 (ULN 130)) OR Both ALT and total bilirubin > ULN OR Total bilirubin > 60 (ULN 30)
Severe Renal Impairment (eGFR < 40)
Treatment with other medications known to potentiate guanfacine's hypotensive effects or cause arrhythmia (specifically antipsychotics (including sultopride, chlorpromazine, thioridazine, amisulpiride, sulpiride, haloperidol), and moxifloxacin, baclofen, verapamil, quinidine, hydroquinidine, dispyramide, amiodarone, dofetilide, ibutilide, sotalol, pimazide, bepridil, cisapride, diphemanil, erythromycin, halofantrine, pentamidine, sparfloxacin, vincamine, alfuzosin, prazosin, terazosin, tamsulosin, amifostine
Weight less than 45kg
Pregnancy (Pre-menopausal women will only be entered into the study of they are surgically sterile or using effective birth control methods: These are abstinence for the period of the study, intrauterine contraception/device, male sexual partners with vasectomy)
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