NCT03116126

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.

Trial Health

55
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
148

participants targeted

Target at below P25 for phase_3 alzheimer-disease

Timeline
Completed

Started Jan 2019

Longer than P75 for phase_3 alzheimer-disease

Geographic Reach
1 country

1 active site

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 4, 2017

Completed
10 days until next milestone

First Posted

Study publicly available on registry

April 14, 2017

Completed
1.7 years until next milestone

Study Start

First participant enrolled

January 4, 2019

Completed
5.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 5, 2024

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 5, 2024

Completed
Last Updated

May 13, 2024

Status Verified

May 1, 2024

Enrollment Period

5.6 years

First QC Date

April 4, 2017

Last Update Submit

May 10, 2024

Conditions

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (9)

  • Tests of Attention: Trails A and B

    12 weeks

  • Digit-symbol substitution

    12 weeks

  • Test of Everyday attention

    12 weeks

  • CANTAB-RVP

    12 weeks

  • Neuropsychiatric Inventory (NPI)

    12 weeks

  • +4 more secondary outcomes

Study Arms (2)

Guanfacine

ACTIVE COMPARATOR
Drug: Guanfacine

Placebo

PLACEBO COMPARATOR
Drug: Placebo

Interventions

2mg oral daily tablet

Guanfacine

inactive oral daily tablet

Placebo

Eligibility Criteria

Age45 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Imperial Memory Unit, Charing Cross Hospital

London, W6 8RF, United Kingdom

Location

Related Publications (1)

  • Hoang K, Watt H, Golemme M, Perry RJ, Ritchie C, Wilson D, Pickett J, Fox C, Howard R, Malhotra PA. Noradrenergic Add-on Therapy with Extended-Release Guanfacine in Alzheimer's Disease (NorAD): study protocol for a randomised clinical trial and COVID-19 amendments. Trials. 2022 Aug 1;23(1):623. doi: 10.1186/s13063-022-06190-3.

Related Links

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Guanfacine

Condition Hierarchy (Ancestors)

DementiaBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesTauopathiesNeurodegenerative DiseasesNeurocognitive DisordersMental Disorders

Intervention Hierarchy (Ancestors)

GuanidinesAmidinesOrganic ChemicalsPhenylacetatesAcids, CarbocyclicCarboxylic Acids

Study Officials

  • Paresh Malhotra, MA BMBCh PhD

    Imperial College London

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 4, 2017

First Posted

April 14, 2017

Study Start

January 4, 2019

Primary Completion

August 5, 2024

Study Completion

August 5, 2024

Last Updated

May 13, 2024

Record last verified: 2024-05

Locations