Guanfacine Treatment for Prefrontal Cognitive Dysfunction in Elderly Subjects

Study Overview
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Brief Summary
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This proposal aims to determine whether low does of the alpha-2A-adrenoceptor agonist guanfacine can improve deficits in prefrontally-mediated cognitive functions in healthy elderly subjects.

Detailed Description
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Primary: To determine whether low does of the α2A-adrenoceptor agonist guanfacine can improve deficits in prefrontally-mediated working memory and executive control functions, in healthy elderly subjects. Subjects will be randomly assigned to receive placebo or guanfacine at one of two dose levels: 0.1 mg, or 0.5 mg daily at bedtime in double-blind fashion for twelve weeks. Secondary: To determine whether guanfacine can favorably influence global status and quality of life (QOL) in healthy elderly subjects. To determine whether low-dose guanfacine is safe and well-tolerated in healthy elderly subjects.

Official Title
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Guanfacine Treatment for Prefrontal Cognitive Dysfunction in Elderly Subjects

Conditions
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Cognitive Aging

Intervention / Treatment
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* Drug: Guanfacine
* Drug: Guanfacine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects enrolled will be nondemented, male and female individuals who meet the following inclusion criteria: 75 years of age or older Fluent in English Stable medical condition for at least 4 weeks prior to Screening visit Stable dose of non-excluded medications for at least 4 weeks prior to Screening visit Exclusion Criteria: Dementia Mild Cognitive Impairment (Amnestic MCI) Clinically significant neurologic disease Clinically significant or unstable medical conditions that would interfere with participation in the trial Known hypersensitivity to guanfacine History of alcohol or substance abuse or dependence within the past 5 years Active major psychiatric disorders, including major depression History of mental retardation Significant abnormalities on clinical laboratories, ECG, or physical examination Impairment of visual or auditory acuity sufficient to interfere with completion of study procedures Education level < 6 years

Ages Eligible for Study
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Minimum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Guanfacine 0.1 mg po qhs<br> | Drug: Guanfacine<br>* Guanfacine 0.1 mg po qhs<br>|
| Experimental: Guanfacine 0.5 mg po qhs<br> | Drug: Guanfacine<br>* Guanfacine 0.5 mg po qhs<br>|
| Placebo Comparator: Placebo po qhs<br> | Drug: Placebo<br>* Placebo po qhs<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean in the Prefrontal Executive Function Z-score (PEF6_6) | The primary outcome measure (PEF6_Z) is the mean of z-scores for 6 executive function tasks (CANTAB: Spatial Working Memory, Stockings of Cambridge, Intradimensiona/Extradimensional Shift, Paired Associates Learning; Stroop Color Word Score, Trail Making Test - B). The score is composed of six component scales coded as z scores that measures cognitive functioning in which higher scores represent better cognitive functioning; therefore, the least squares means listed here represent mean outcome changes from baseline | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) | The seven-point scale was collapsed into 3 groups and coded as a three-level ordinal scale of global status, representing ordered levels of worse (including minimally, moderately and markedly worse), unchanged, and improved (including minimally, moderately, and markedly improved) global status. | 12 weeks | 
| Quality of Life (SF-36 MCS) | Quality of Life (QOL) was assessed using the SF-36 (36-Item Short-Form Health Survey; QualityMetric, Lincoln, RI), MCS subscale. The SF-36 is a self-administered general health-related quality of life scale with 36 items. The MCS subscale has been shown to be responsive in psychoactive drug trials. The score range is 0-100. Higher scores represent better mental health; therefore, the least squares means listed here represent mean outcome changes from baseline. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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guanfacine, aging, cognitive aging, prefrontal cognitive function, executive function, prefrontal cortex