Noradrenergic Add-on Therapy With Guanfacine (NorAD)

June 22, 2022 updated by: Imperial College London

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Anticipated)

160

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

45 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Drug: Placebo
inactive oral daily tablet
Active Comparator: Guanfacine
Drug: Guanfacine
2mg oral daily tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cognition as measured by the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog)
Time Frame: 12 weeks
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tests of Attention: Trails A and B
Time Frame: 12 weeks
Neuropsychological test sensitive detecting cognitive impairment associated with dementia/AD.
12 weeks
Digit-symbol substitution
Time Frame: 12 weeks
Neuropsychological test sensitive detecting cognitive impairment associated with dementia/AD.
12 weeks
Test of Everyday attention
Time Frame: 12 weeks
Neuropsychological test sensitive detecting cognitive impairment associated with dementia/AD.
12 weeks
CANTAB-RVP
Time Frame: 12 weeks
Neuropsychological test sensitive detecting cognitive impairment associated with dementia/AD.
12 weeks
Neuropsychiatric Inventory (NPI)
Time Frame: 12 weeks
Examination and scoring of behavioural domains to determine the frequency and severity of behaviour with the patient and caregiver.
12 weeks
Zarit Burden Interview (22 Item)
Time Frame: 12 weeks
Examination and scoring of behavioural domains to determine the frequency and severity of behaviour with the patient and caregiver.
12 weeks
Alzheimer's Disease Co-operative Study - Activities of Daily Living Inventory (ADCS-ADL)
Time Frame: 12 weeks
Examination and scoring of behavioural domains to determine the frequency and severity of behaviour with the patient and caregiver.
12 weeks
Blood pressure
Time Frame: 12 weeks
Measure of side effects.
12 weeks
Epworth Sleepiness Scale
Time Frame: 12 weeks
Measure of side effects.
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Imperial College London

Investigators

  • Principal Investigator: Paresh Malhotra, MA BMBCh PhD, Imperial College London

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 4, 2019

Primary Completion (Anticipated)

December 31, 2022

Study Completion (Anticipated)

December 31, 2022

Study Registration Dates

First Submitted

April 4, 2017

First Submitted That Met QC Criteria

April 11, 2017

First Posted (Actual)

April 14, 2017

Study Record Updates

Last Update Posted (Actual)

June 23, 2022

Last Update Submitted That Met QC Criteria

June 22, 2022

Last Verified

June 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRAS 171996

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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