Antioxidant Cocktail for Stroke Prevention

Overseen By Shawn Bolin, MS

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Wisconsin, Madison

Must not be taking: Cardiovascular medications, NSAIDs

Disqualifiers: Hypertension, Diabetes, Smoking, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to assess how an antioxidant cocktail affects blood flow in the brain, potentially helping to prevent strokes. Participants will receive either the antioxidant cocktail, which combines substances that may reduce oxidative stress, or a placebo before undergoing an MRI. The study seeks healthy individuals who do not smoke, have stable blood pressure, and do not have conditions like diabetes or heart disease. This trial offers a chance to contribute to important research and possibly improve future stroke prevention. As an unphased trial, it provides a unique opportunity to contribute to groundbreaking research that could shape future stroke prevention strategies.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking all current medications, but it does require stopping hormonal birth control at least one month before the first study visit if it's used for contraception only. Cardiovascular medication use is also an exclusion criterion, so you may need to stop those if applicable.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that combining alpha-lipoic acid and vitamin E, both part of the antioxidant mix, helps protect cells from damage. A review of studies found that alpha-lipoic acid does not increase the risk of side effects from treatment, reassuring those considering joining the trial.

Although specific safety data for this exact antioxidant mix in humans is not available, the individual ingredients, such as vitamin C, vitamin E, and alpha-lipoic acid, are generally safe. Many people take these vitamins as supplements without issues. However, as with any treatment, some individuals might experience minor side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the Antioxidant Cocktail for stroke prevention because it offers a novel approach, distinct from the traditional use of blood thinners and clot-busting drugs. This cocktail combines vitamin C, vitamin E, and alpha lipoic acid, which are antioxidants known for combating oxidative stress, a key player in stroke development. Unlike current treatments that primarily focus on blood flow, this antioxidant mix targets the underlying oxidative damage that can lead to strokes. By potentially reducing this damage, the cocktail may offer a unique preventive strategy and enhance stroke prevention outcomes.

What evidence suggests that this trial's treatments could be effective for stroke prevention?

This trial will compare an Antioxidant Cocktail with a placebo to evaluate its potential in stroke prevention. Research has shown that antioxidants like vitamin C, vitamin E, and alpha-lipoic acid can reduce brain damage from strokes by neutralizing harmful free radicals, which are unstable molecules that can damage cells. Studies have found that combining alpha-lipoic acid and vitamin E is especially effective in reducing oxidative damage, a type of harm caused by these free radicals. While individual antioxidants have been studied, the combination is believed to offer stronger protection. Ongoing research aims to better understand how this mix might improve blood flow in the brain. ^{1 2 3 4 6}

Who Is on the Research Team?

William G Schrage, PhD

Principal Investigator

University of Wisconsin, Madison

Are You a Good Fit for This Trial?

Healthy adults aged 18-40 can join this study on reactive oxygen species and brain blood flow. Excluded are those with high blood pressure, glucose levels, or a history of heart, liver, kidney diseases; smokers; certain medication users; MRI contraindications; women with irregular menstrual cycles or using hormonal birth control (except copper IUDs).

Exclusion Criteria

You are sensitive to NSAIDs (non-steroidal anti-inflammatory drugs).

I am taking medication for my heart condition.

I have been diagnosed with sleep apnea.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo CBF testing in MRI under normoxia and hyperoxia conditions with either placebo or antioxidant cocktail

6 months

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Antioxidant Cocktail
• Placebo

Trial Overview The trial is testing an antioxidant cocktail against a placebo in 30 healthy participants to understand its effect on cerebral blood flow. The study spans over six months with two visits.

How Is the Trial Designed?

Group I: Antioxidant Cocktail Experimental Treatment 1 Intervention

The first dose will be 500 mg vitamin C, 200 IU vitamin E, and 300 mg of alpha lipoic acid 120 minutes before MRI. The second dose will be 500 mg vitamin C, 400 IU vitamin E, and 300 mg of alpha lipoic acid 60 minutes before MRI.

Group II: Placebo Active Control 1 Intervention

Placebo 120 minutes before MRI, followed by another dose of placebo 60 minutes before MRI.

Who Is Running the Clinical Trial?

University of Wisconsin, Madison

Lead Sponsor

Trials

1,249

Recruited

3,255,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

In a multicenter, randomized, placebo-controlled study involving 252 acute ischemic stroke patients, edaravone showed a significant improvement in functional outcomes compared to placebo, as measured by the modified Rankin Scale (p = 0.0382).

Edaravone acts as a neuroprotective agent by inhibiting vascular endothelial cell injury and reducing neuronal damage, suggesting its potential as an effective treatment for acute ischemic stroke when administered within 72 hours of onset.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of a novel free radical scavenger, edaravone (MCI-186), on acute brain infarction. Randomized, placebo-controlled, double-blind study at multicenters. [2022]

A systematic review of 10 studies involving 387,076 participants found that higher intakes of flavanones are linked to a reduced risk of stroke, with a relative risk of 0.85 for those consuming the highest amounts compared to the lowest.

Flavan-3-ols also showed a potential protective effect against stroke, with a 14% reduction in risk associated with a daily increase of 200 mg, suggesting that foods rich in these flavonoids, like citrus fruits, may help lower stroke risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A meta-analysis of prospective cohort studies of flavonoid subclasses and stroke risk. Li, XQ., Wang, C., Yang, T., et al.[2022]

Antioxidant compounds may offer potential benefits in preventing or treating acute ischemic stroke by reducing brain damage caused by excessive free radicals, as highlighted in various observational studies and clinical trials.

Promising antioxidants such as dehydroascorbic acid, alpha-tocotrienol, and flavonoids have shown effectiveness in animal models, but there are challenges in translating these results to human patients, indicating a need for improved research methodologies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary antioxidants as potential pharmacological agents for ischemic stroke. Cherubini, A., Ruggiero, C., Morand, C., et al.[2019]

In a study involving male Sprague-Dawley rats, pretreatment with resveratrol significantly reduced brain damage after ischemic stroke, showing its potential as a neuroprotective agent when administered before or shortly after blood flow is restored.

Combining low doses of resveratrol with lipoic acid also provided significant neuroprotection, and a new compound (UPEI-201) created from these two showed promise in protecting against ischemia-induced damage, suggesting a multi-pathway approach to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Co-administration of resveratrol and lipoic acid, or their synthetic combination, enhances neuroprotection in a rat model of ischemia/reperfusion. Saleh, MC., Connell, BJ., Rajagopal, D., et al.[2021]

Antioxidants may help reduce ischemic cerebral injury by decreasing arterial vasospasm and infarct size, but clinical evidence supporting these benefits is still lacking.

Light-to-moderate alcohol intake could protect against atherosclerosis, a major cause of ischemic stroke, by preventing LDL oxidation and reducing platelet aggregation, although heavy drinking may worsen ischemic conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxidants, antioxidants, alcohol and stroke. Hillbom, M.[2021]

In a study involving 48 acute ischaemic stroke patients, supplementation with antioxidants (800 IU of alpha-tocopherol and 500 mg of vitamin C) within 12 hours of stroke onset significantly increased antioxidant levels and total antioxidant capacity compared to a control group.

The treatment group also showed a significant reduction in plasma malondialdehyde (MDA), indicating less oxidative damage, and lower C-reactive protein (CRP) levels, suggesting a potential anti-inflammatory effect after 14 days of supplementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antioxidant supplementation enhances antioxidant capacity and mitigates oxidative damage following acute ischaemic stroke. Ullegaddi, R., Powers, HJ., Gariballa, SE.[2013]

Conventional radical scavenging antioxidants have shown limited effectiveness in treating ischemic stroke, highlighting the need for more potent alternatives.

NXY-059, a spin trap nitrones agent, has demonstrated effectiveness in animal models of cerebral ischemia and is currently undergoing phase III clinical trials, suggesting promising potential for treating ischemic stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nitrone spin on cerebral ischemia. Doggrell, SA.[2007]

In a study of 72 stroke patients over 12 months, supplementation with n-3 fatty acids showed a trend towards lower mortality rates, suggesting potential benefits for stroke survivors' long-term health.

Despite the lack of significant differences in rehabilitation outcomes among the treatment groups, the study highlighted the prevalence of malnutrition in stroke patients, indicating that dietary supplementation may be important for improving overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is antioxidant and n-3 supplementation able to improve functional status in poststroke patients? Results from the Nutristroke Trial. Garbagnati, F., Cairella, G., De Martino, A., et al.[2022]

Diet plays a significant role in reducing the risk of stroke, particularly in the elderly, due to the presence of bioactive compounds with antioxidant and anti-inflammatory properties.

Several dietary bioactive compounds have shown promising results in reducing cerebral damage in models of cerebral ischemia, suggesting they could be potential candidates for new neuroprotective strategies to protect the brain before a stroke occurs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuroprotective diets for stroke. Ayuso, MI., Gonzalo-Gobernado, R., Montaner, J.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2925278/

THERAPEUTIC PERSPECTIVES ON THE COMBINATION OF ... This review summarizes recent findings showing that the combination of alpha-lipoic acid plus vitamin E has beneficial effects in reducing oxidative damage.

2. withpower.com withpower.com/trial/phase-cerebrovascular-disorders-7-2023-be55c

Antioxidant Cocktail for Stroke Prevention Research shows that antioxidants can help reduce brain damage caused by strokes by neutralizing harmful free radicals. Studies on individual antioxidants like ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0271531705002812

Therapeutic perspectives on the combination of α-lipoic ... This review summarizes recent findings showing that the combination of ALA plus VE has beneficial effects in reducing oxidative damage in ischemic or other ...

4. researchgate.net researchgate.net/publication/45828245_Therapeutic_perspectives_on_the_combination_of_a-lipoic_acid_and_vitamin_E

Therapeutic perspectives on the combination of α-lipoic ... This review summarizes recent findings showing that the combination of alpha-lipoic acid plus vitamin E has beneficial effects in reducing ...

5. acc.org acc.org/Latest-in-Cardiology/Articles/2022/12/05/20/59/Study-Identifies-Some-Supplements-That-Benefit-CV-Health

Study Identifies Some Supplements That Benefit CV Health Vitamin C, Vitamin D, Vitamin E and selenium showed no effect on long-term cardiovascular disease outcomes or type-2 diabetes risk. And beta ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7603186/

Safety Evaluation of α-Lipoic Acid Supplementation A meta-analysis of extracted data suggested that supplementation with ALA was not associated with an increased risk of any treatment-emergent adverse event (all ...