Antioxidants + Nitroglycerin for Cardiovascular Health

(NO-Stress Trial)

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Augusta University

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

Compensation: Varies

Number of Visits: 4

Duration: 2 days

74 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Antioxidants + Nitroglycerin for cardiovascular health?

Research suggests that nitroglycerin, when combined with antioxidants like N-acetylcysteine, can enhance the production of beneficial compounds in the body, potentially improving heart and blood vessel health. Additionally, nitroglycerin has been shown to be effective in treating coronary artery disease by improving exercise time and reducing symptoms. ^{1 2 3 4 5}

Is the combination of antioxidants and nitroglycerin safe for human use?

Research suggests that nitroglycerin, when used with antioxidants like N-acetylcysteine, may have beneficial effects on the liver and brain by reducing harmful substances and increasing protective ones. However, nitroglycerin can cause tolerance, meaning its effects may decrease over time, and it can affect blood pressure and heart rate. Overall, it appears to be safe when used appropriately, but individual responses can vary. ^{1 2 3 6 7}

How does the drug Antioxidant cocktail with nitroglycerin differ from other cardiovascular treatments?

This treatment is unique because it combines antioxidants with nitroglycerin, which may help prevent nitroglycerin tolerance by reducing oxidative stress and improving the bioactivation of nitroglycerin to nitric oxide, potentially enhancing its effectiveness for cardiovascular health. ^{1 2 3 8 9}

What is the purpose of this trial?

This trial will test if taking vitamins and antioxidants can improve heart health in people who had stressful childhoods, especially those from low-income backgrounds. The study will compare the effects of the antioxidant mix to a non-active substance.

Research Team

Ryan Harris, PhD

Principal Investigator

Augusta University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

References

1. United States pubmed.ncbi.nlm.nih.gov

Biochemical, hemodynamic, and vascular evidence concerning the free radical hypothesis of nitrate tolerance. [2019]

2. Poland pubmed.ncbi.nlm.nih.gov

Influence of N-acetylcysteine on bioactivation of nitroglycerin to nitric oxide and S-nitrosothiols in the liver and brain of mice. [2013]

3. United States pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, placebo-controlled, crossover study to assess the immediate effect of sublingual glyceryl trinitrate on the ankle brachial pressure index, claudication, and maximum walking distance of patients with intermittent claudication. [2019]

4. Switzerland pubmed.ncbi.nlm.nih.gov

A randomized crossover evaluation of antianginal efficacy and safety of nitrolingual-spray and nitroglycerin tablet form in coronary artery disease patients. [2017]

5. United States pubmed.ncbi.nlm.nih.gov

Effect of Nitroglycerin on the Performance of MR Coronary Angiography. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Blood levels after sublingual nitroglycerin. [2022]

7. India pubmed.ncbi.nlm.nih.gov

Attenuation of pressor response following intubation: Efficacy of nitro-glycerine lingual spray. [2020]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Coronary vasodilation by the use of sublingual nitroglycerin using 64-slice dual-source coronary computed tomography angiography. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Preventive effect of tetramethylpyrazine on nitroglycerin-tolerance in rats by improving oxidative stress and ribosome homeostasis. [2022]