Antioxidants + Nitroglycerin for Cardiovascular Health

(NO-Stress Trial)

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Augusta University

Must not be taking: Vascular tone medications

Disqualifiers: Cardiovascular, Renal, Pulmonary, others

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

Compensation: Varies

Number of Visits: 4

Duration: 2 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how early-life stress affects heart health. Researchers will test the effects of an antioxidant mix and nitroglycerin spray, a medication for chest pain, on cardiovascular function. Participants will undergo assessments involving blood samples and artery function tests. Suitable candidates include men and premenopausal women aged 18-40 who have experienced early-life stress and are lean, overweight, or have a BMI up to 39. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research on heart health and stress.

Will I have to stop taking my current medications?

The trial excludes participants who use medications that affect vascular tone, so you may need to stop taking such medications to participate.

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

Research has shown that the antioxidant mix, which includes Vitamin C, Vitamin E, and Alpha Lipoic Acid, is usually well-tolerated. Studies have found that Alpha Lipoic Acid, a key component of the mix, is safe for various groups, including those with different health conditions. This suggests the antioxidant mix might be safe for many individuals.

Nitroglycerin, used as a spray, commonly treats chest pain from heart disease. It is generally safe, though some may experience mild side effects like a slight increase in heart rate or a drop in blood pressure. These side effects are typically not serious.

Both treatments have been used previously and have demonstrated safety in many cases. However, consulting a healthcare provider is always important for any concerns or questions about side effects or safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this treatment because it combines an antioxidant cocktail with a nitroglycerin spray to potentially improve cardiovascular health. Unlike typical treatments like statins or beta-blockers that manage cholesterol or blood pressure, this approach focuses on enhancing blood vessel function directly. The antioxidants used, including Vitamin C, Vitamin E, and Alpha Lipoic Acid, target oxidative stress, which is a key factor in cardiovascular diseases. Additionally, the sub-lingual nitroglycerin spray is designed to quickly improve blood vessel dilation, offering a rapid response that could complement the long-term benefits of antioxidants. This dual-action strategy has the potential to offer a more comprehensive improvement in cardiovascular health.

What evidence suggests that this trial's treatments could be effective for cardiovascular health?

Research has shown that antioxidants can benefit heart health. One study found that higher Vitamin C levels in the blood linked to a 9% lower risk of heart failure. Another study indicated that combining Alpha Lipoic Acid (ALA) with Vitamin E reduces damage from poor blood flow. ALA may also protect the heart by lowering bad cholesterol and improving blood pressure. In this trial, participants may receive an antioxidant cocktail to assess its effects on cardiovascular health.

For nitroglycerin, studies have shown that sprays used under the tongue help people with stable angina (chest pain) exercise longer. Nitroglycerin widens blood vessels, increasing blood flow to the heart. Participants in this trial may receive nitroglycerin to evaluate its impact on heart health. These findings support the potential benefits of both treatments for heart health. ^{2 4 6 7 8}

Who Is on the Research Team?

Ryan Harris, PhD

Principal Investigator

Augusta University

Are You a Good Fit for This Trial?

The NO-Stress trial is for men and premenopausal women aged 18-40, who are lean, overweight, or obese with a BMI of 39 or less. Participants must have records of their socioeconomic status during childhood. Those with cardiovascular and other major diseases, postmenopausal women, individuals with class 3 obesity (BMI over 40), or those on meds affecting blood vessel tone cannot join.

Inclusion Criteria

Patients must have documented childhood SES

My BMI is 39 or less.

I am a man or a premenopausal woman aged between 18 and 40.

Exclusion Criteria

I have a heart, kidney, lung, liver, brain, or metabolic condition.

My BMI is over 40, classifying me as having class 3 obesity.

I am a woman who has gone through menopause.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Blood samples, flow-mediated dilation, and nitroglycerin mediated dilation are performed at baseline

1 day

1 visit (in-person)

Treatment

Participants receive a single dose oral antioxidant cocktail or placebo, with assessments 2 hours post-treatment

2 days

2 visits (in-person)

Biopsy (Optional)

Participants may undergo a subcutaneous gluteal/hip fat biopsy for further analysis

1 day

1 visit (in-person)

Follow-up

Participants are monitored for any adverse effects and overall health post-treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Antioxidant cocktail
• Biopsy
• NMD; 0.4mg sub-lingual nitroglycerin spray
• Placebo

Trial Overview This study tests the effects of an antioxidant cocktail and a nitroglycerin spray under the tongue against a placebo in understanding how early life stress impacts heart health. It also involves taking small tissue samples to study changes at the cellular level.

How Is the Trial Designed?

Group I: Biopsy Experimental Treatment 1 Intervention

Following an overnight fast, a subcutaneous gluteal/hip fat biopsy sample will be obtained from each subject under local anesthesia, with adipose tissue (\~2x1.5x1.5cm) to be harvested and placed immediately in physiological saline solution (PSS): Small arteries, 100 to 150 um in diameter, will be dissected from the fat under a dissecting microscope, transferred to an arteriographic bath chamber, and cannulated for pressurized myography.

Group II: Antioxidant Cocktail Experimental Treatment 3 Interventions

Following an overnight fast, blood samples, flow-mediated dilation, and nitroglycerin mediated dilation (NMD; 0.4mg sub-lingual nitroglycerin spray) will be performed at baseline and 2 hours following either a single dose oral antioxidant cocktail (1000 mg Vitamin C, 600 IU vitamin E, 600 mg Alpha Lipoic Acid) or placebo on two days separated by at least 72 hours.

Who Is Running the Clinical Trial?

Augusta University

Lead Sponsor

Trials

219

Recruited

85,900+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7761826/

Vitamin C and Cardiovascular Disease: An Update - PMC A mean follow-up of 12.8 years showed that every 20 μmol/L increase in plasma Vitamin C was associated with a 9% relative reduction in the risk of HF. [140].

2. 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 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3730828/

Effects of triple antioxidant therapy on measures ... We evaluated the effects of a combination triple antioxidant therapy on measures of cardiovascular autonomic neuropathy (CAN) and myocardial blood flow ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0022316622162085

α-Lipoic Acid and Cardiovascular Disease ALA may protect against CVD by impacting LDL oxidation, blood lipids, plaque formation, and hypertension, and may act as a protective agent.

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/PMC5456308/

Antioxidants and Cardiovascular Risk Factors - PMC The aim of this review is to evaluate the antioxidant effects on the main cardiovascular risk factors including hypertension, dyslipidemia, diabetes.

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

Safety Evaluation of α-Lipoic Acid Supplementation ALA supplementation was safe, even in subsets of studies categorized according to smoking habit, cardiovascular disease, presence of diabetes, pregnancy status, ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02966665?cond=%22Hypertension%22&intr=%22Tocopherol%22&viewType=Table&rank=5

Study Details | : Vascular Function in Health and Disease Many control mechanisms exist which successfully match the supply of blood with the metabolic demand of various tissues under wide-ranging conditions.