Guanfacine NorAD (NCT03116126) is a Phase 3 clinical trial evaluating extended-release guanfacine as a noradrenergic add-on therapy for Alzheimer's disease (AD). The trial, conducted at Imperial College London, investigates whether adding guanfacine to standard cholinergic therapy (donepezil, rivastigmine, or galantamine) can improve cognitive function, particularly attention, in patients with mild to moderate AD.[1]
The trial is named NorAD (Noradrenergic Add-on Therapy) and represents a novel approach to AD treatment by targeting the noradrenergic system, which is known to be compromised in Alzheimer's disease and plays a critical role in attention and executive function.[2]
Both noradrenaline (norepinephrine) levels and attentional performance have been shown to be reduced in Alzheimer's disease. The locus coeruleus, the primary source of noradrenergic innervation in the brain, undergoes significant degeneration in AD, contributing to:
Guanfacine is an alpha-2A adrenergic receptor agonist that:
The rationale for using guanfacine in AD is that modulating the noradrenergic deficit, in addition to standard cholinergic treatment, could have significant positive effects on cognition, particularly in patients with attentional impairments.[1]
| Parameter | Value |
|---|---|
| NCT Number | NCT03116126 |
| Official Title | Randomised Clinical Trial of Noradrenergic Add-on Therapy With Extended-Release Guanfacine in Alzheimer's Disease |
| Acronym | NorAD |
| Phase | Phase 3 |
| Status | Active, not recruiting |
| Design | Single-centre, randomised, parallel-group, double-blind, controlled |
| Start Date | January 4, 2019 |
| Completion Date | August 5, 2024 (estimated) |
| Enrollment | 148 patients (actual) |
| Arm | Type | Intervention |
|---|---|---|
| Guanfacine | Active Comparator | Drug: Guanfacine (2mg oral daily tablet) |
| Placebo | Placebo Comparator | Drug: Placebo (inactive oral daily tablet) |
| Measure | Description | Time Frame |
|---|---|---|
| Cognition (ADAS-Cog) | Alzheimer's Disease Assessment Scale-Cognitive subscale measuring memory, language, praxis, attention, and other cognitive abilities | 12 weeks |
The ADAS-Cog is the gold standard cognitive testing instrument in AD clinical trials, consisting of 11 tasks measuring disturbances in core symptoms of AD.[1]
| Measure | Description | Time Frame |
|---|---|---|
| Trails A and B | Tests of attention - neuropsychological tests sensitive to cognitive impairment | 12 weeks |
| Digit-symbol substitution | Neuropsychological test sensitive to cognitive impairment | 12 weeks |
| Test of Everyday attention | Neuropsychological test for attention assessment | 12 weeks |
| CANTAB-RVP | Cambridge Neuropsychological Test Automated Battery - Rapid Visual Processing | 12 weeks |
| Neuropsychiatric Inventory (NPI) | Behavioral domains frequency and severity | 12 weeks |
| Zarit Burden Interview (22 Item) | Caregiver burden assessment | 12 weeks |
| ADCS-ADL | Alzheimer's Disease Co-operative Study - Activities of Daily Living Inventory | 12 weeks |
| Blood pressure | Safety/side effect measure | 12 weeks |
| Epworth Sleepiness Scale | Side effect measure | 12 weeks |
| Facility | City | Country |
|---|---|---|
| Imperial Memory Unit, Charing Cross Hospital | London | United Kingdom |
This trial investigates whether the combination of guanfacine (noradrenergic enhancement) with standard cholinergic therapy (donepezil, rivastigmine, or galantamine) provides superior cognitive benefits compared to cholinergic therapy alone. The rationale is: