Noradrenergic Add-on Therapy With Guanfacine

Alzheimer Disease Clinical Trial

— NorAD  

Official title:

Randomised Clinical Trial of Noradrenergic Add-on Therapy With Extended-Release Guanfacine in Alzheimer's Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03116126
• Other study ID #: IRAS 171996
• Status: Recruiting
• Phase: Phase 3
• Start date: January 4, 2019
• Est. completion date: December 31, 2022

Study information

• Verified date: June 2022
• Source: Imperial College London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 160
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years and older

Eligibility

Inclusion Criteria:

• Outpatients
• 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)

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

Drug:
• Guanfacine
2mg oral daily tablet
• Placebo
inactive oral daily tablet

Locations

Country	Name	City	State
United Kingdom	Imperial Memory Unit, Charing Cross Hospital	London

Sponsors (1)

Lead Sponsor	Collaborator
Imperial College London

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cognition as measured by the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog)	The ADAS-Cog is used to determine the extent of cognitive decline in AD. It is a common cognitive testing instrument in clinical trials consisting of 11 tasks measuring disturbances in memory, language, praxis, attention and other cognitive abilities that are core symptoms of AD.	12 weeks
Secondary	Tests of Attention: Trails A and B	Neuropsychological test sensitive detecting cognitive impairment associated with dementia/AD.	12 weeks
Secondary	Digit-symbol substitution	Neuropsychological test sensitive detecting cognitive impairment associated with dementia/AD.	12 weeks
Secondary	Test of Everyday attention	Neuropsychological test sensitive detecting cognitive impairment associated with dementia/AD.	12 weeks
Secondary	CANTAB-RVP	Neuropsychological test sensitive detecting cognitive impairment associated with dementia/AD.	12 weeks
Secondary	Neuropsychiatric Inventory (NPI)	Examination and scoring of behavioural domains to determine the frequency and severity of behaviour with the patient and caregiver.	12 weeks
Secondary	Zarit Burden Interview (22 Item)	Examination and scoring of behavioural domains to determine the frequency and severity of behaviour with the patient and caregiver.	12 weeks
Secondary	Alzheimer's Disease Co-operative Study - Activities of Daily Living Inventory (ADCS-ADL)	Examination and scoring of behavioural domains to determine the frequency and severity of behaviour with the patient and caregiver.	12 weeks
Secondary	Blood pressure	Measure of side effects.	12 weeks
Secondary	Epworth Sleepiness Scale	Measure of side effects.	12 weeks

External Links

•   HRA research summary