Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Noradrenergic Add-on Therapy With Guanfacine (NorAD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03116126
Recruitment Status : Recruiting
First Posted : April 14, 2017
Last Update Posted : July 31, 2020
Sponsor:
Information provided by (Responsible Party):
Imperial College London

Brief 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.


Condition or disease Intervention/treatment Phase
Alzheimer Disease Drug: Guanfacine Drug: Placebo Phase 3

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Randomised Clinical Trial of Noradrenergic Add-on Therapy With Extended-Release Guanfacine in Alzheimer's Disease
Actual Study Start Date : January 4, 2019
Estimated Primary Completion Date : March 31, 2021
Estimated Study Completion Date : March 31, 2021


Arm Intervention/treatment
Active Comparator: Guanfacine Drug: Guanfacine
2mg oral daily tablet

Placebo Comparator: Placebo Drug: Placebo
inactive oral daily tablet




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Tests of Attention: Trails A and B [ Time Frame: 12 weeks ]
    Neuropsychological test sensitive detecting cognitive impairment associated with dementia/AD.

  2. Digit-symbol substitution [ Time Frame: 12 weeks ]
    Neuropsychological test sensitive detecting cognitive impairment associated with dementia/AD.

  3. Test of Everyday attention [ Time Frame: 12 weeks ]
    Neuropsychological test sensitive detecting cognitive impairment associated with dementia/AD.

  4. CANTAB-RVP [ Time Frame: 12 weeks ]
    Neuropsychological test sensitive detecting cognitive impairment associated with dementia/AD.

  5. 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.

  6. 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.

  7. 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.

  8. Blood pressure [ Time Frame: 12 weeks ]
    Measure of side effects.

  9. Epworth Sleepiness Scale [ Time Frame: 12 weeks ]
    Measure of side effects.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   45 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03116126


Locations
Layout table for location information
United Kingdom
Imperial Memory Unit, Charing Cross Hospital Recruiting
London, United Kingdom, W6 8RF
Contact: Team    020 3311 5228    MEMORY.RESEARCH@IMPERIAL.NHS.UK   
Sponsors and Collaborators
Imperial College London
Investigators
Layout table for investigator information
Principal Investigator: Paresh Malhotra, MA BMBCh PhD Imperial College London
Additional Information:
Layout table for additonal information
Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT03116126    
Other Study ID Numbers: IRAS 171996
First Posted: April 14, 2017    Key Record Dates
Last Update Posted: July 31, 2020
Last Verified: July 2020

Layout table for additional information
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
Additional relevant MeSH terms:
Layout table for MeSH terms
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Guanfacine
Antihypertensive Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs