Memory and Antioxidants in Vascular Impairment Trial

Study Overview
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Brief Summary
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This is a 24-week randomized, double-blind, placebo-controlled parallel group design study involving Vascular cognitive impairment-no dementia (VCIND) patients to evaluate the efficacy and safety of oral NAC supplementation (2,400 mg daily) as an add-on therapy to improve cognitive function in patients undergoing cardiac rehabilitation (CR). The CR program consists of a harmonized aerobic and resistance training in a supervised group setting. Eligible patients will be randomized to receive NAC (four 600 mg capsules given as 2 capsules in the morning and 2 capsules in the evening) or matching placebo capsules. The initial NAC dosage will be 600mg/day (one 600mg capsule in the morning) for the first week, followed by 1,200 mg/day (one 600 mg capsule in the morning, one 600mg capsule in the evening) for the second week, followed by 1,800 mg/day (two 600mg capsules in the morning, one 600mg capsule in the evening) for third week, followed by 2,400mg/day (two 600mg capsules in the morning, two 600mg capsules in the evening) for the following 21 weeks.

Official Title
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Efficacy and Safety of N-acetylcysteine (NAC) in Patients With Mild Vascular Cognitive Impairment

Conditions
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Vascular Cognitive Impairment no Dementia

Intervention / Treatment
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* Drug: N Acetylcysteine
* Other: Placebo oral capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females aged 55-80 years. MoCA score of less than 28. Modest deficits (1 SD below population norm) in executive function, memory, processing speed, or working memory based on the 60-minute battery recommended by the NINDS-CSN. Speaks and understands English. Enrollment in the Cardiac Rehabilitation program at the University Health Network Toronto Rehabilitation Institute. Exclusion Criteria: A history of stroke A history of epilepsy Uncontrolled asthma (requiring hospitalization or ER visit in the last 3 months by patient report) Uncontrolled diabetes (clinical determination) Severe hypo/hypertension (clinical determination) Uncontrolled hypercholesterolemia (clinical determination) Presence of significant medical illnesses (Severely disturbed liver function, Severely disturbed kidney function, Severely disturbed lung function, HIV, HBV and/or HCV infection, Malignant tumors) A current neurological condition (Parkinson's disease, Multiple sclerosis, Significant traumatic brain injury) Major psychiatric condition (Current major depressive disorder, Schizophrenia, Bipolar disorder, Substance use disorder (alcohol abuse, heavy smoking (20 cigarettes or more/day)) Contraindication to MRI or MRS (e.g. metal in body, pacemaker). Contraindication to NAC (documented allergy) or allergy to lactose. Daily Nitroglycerin use. Bleeding disorders (e.g. hemophilia, Thrombotic Thrombocytopenic Purpura) and/or elective surgery within 30 days. Volunteers who currently participate in another pharmacological study.

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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 |
| --- | --- |
| Active Comparator: N-acetylcysteine<br>Participants randomized into the N-acetylcysteine arm will be receiving N-acetylcysteine for 24 weeks. | Drug: N Acetylcysteine<br>* Patients will be randomized to receive N Acetylcysteine (NAC) (four 600 mg capsules given as 2 capsules in the morning and 2 capsules in the evening). The initial NAC dosage will be 600mg/day (one 600mg capsule in the morning) for the first week, followed by 1,200 mg/day (one 600 mg capsule in the morning, one 600mg capsule in the evening) for the second week, followed by 1,800 mg/day (two 600mg capsules in the morning, one 600mg capsule in the evening) for third week, followed by 2,400mg/day (two 600mg capsules in the morning, two 600mg capsules in the evening) for the following 21 weeks.<br>* Other names: NPN 80004844;|
| Placebo Comparator: Placebo<br>Participants randomized into the placebo arm will be receiving placebo for 24 weeks. | Other: Placebo oral capsule<br>* Patients will receive four placebo capsules (lactose-based filler) given as 2 capsules in the morning and 2 capsules in the evening, which will be prepared to mimic the weight of the experimental capsules.The initial placebo dosage will be 600mg/day (one 600mg capsule in the morning) for the first week, followed by 1,200 mg/day (one 600 mg capsule in the morning, one 600mg capsule in the evening) for the second week, followed by 1,800 mg/day (two 600mg capsules in the morning, one 600mg capsule in the evening) for third week, followed by 2,400mg/day (two 600mg capsules in the morning, two 600mg capsules in the evening) for the following 21 weeks.<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in executive function | Differences in executive function composite z scores between experimental and placebo groups at 6 months. Executive function will be based on the trail test B found in the 60-minute battery recommended by the National Institute of Neurological Disorders and Stroke-Canadian Stroke Network (NINDS-CSN) harmonized standards. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in processing speed | Differences in processing speed composite z scores between experimental and placebo groups at 6 months. Processing speed will be based on the symbol digit modalities test found in the 60-minute battery recommended by the NINDS-CSN. | 6 months | 
| Change in memory | Differences in memory composite z scores between experimental and placebo groups at 6 months. Memory will be based on the Rey Complex Figure Test found in the 60-minute battery recommended by the NINDS-CSN. | 6 months |