Improving blood vessel function in African Americans using galantamine

Enhancing Parasympathetic Activity to Improve Endothelial Dysfunction, Vascular Oxidative Stress in African Americans

This study is testing if a medication called galantamine can improve blood vessel function and reduce stress on the blood vessels in African Americans who may be at higher risk for heart problems.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 160 (estimated)
• Ages: 18 Years to 60 Years
• Sex: All
• Sponsor: Vanderbilt University Medical Center (Academic / other)
• Locations: 1 site (Nashville, Tennessee)
• Trial ID: NCT04769206 on ClinicalTrials.gov

What this trial studies

This study aims to enhance parasympathetic activity to improve endothelial dysfunction and reduce vascular oxidative stress in African Americans. Participants will receive either galantamine or a placebo for three months, with assessments of endothelial cell function and oxidative stress markers. The study will measure changes in vascular reactivity in response to ischemia, focusing on the role of NADPH oxidase and inflammatory mediators. The research addresses the higher cardiovascular disease risk in African Americans by targeting underlying mechanisms of endothelial dysfunction.

Who should consider this trial

Good fit: Ideal candidates are African American men and women aged 18 to 60 with a BMI greater than 28.

Not a fit: Patients with a history of significant cardiovascular events or uncontrolled hypertension may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved vascular health and reduced cardiovascular disease risk in African Americans.

How similar studies have performed: Previous studies have shown promise in using parasympathetic stimulation to mitigate oxidative stress and inflammation, suggesting potential success for this approach.

Eligibility criteria

Inclusion Criteria:

1. African American women and men
2. Age 18 to 60 years old
3. BMI \>28

Exclusion Criteria:

1. Individuals with a history of physician diagnosed myocardial infarction, angina, heart failure, stroke, or transient ischemic attack, or who had undergone an invasive procedure for CVD (coronary artery bypass graft, angioplasty, valve replacement, pacemaker placement or other vascular surgeries)
2. Uncontrolled hypertension defined as persistent blood pressure \>140/90 despite the use of anti-hypertensive agents.
3. Diabetes Mellitus type 1 or type 2, as defined by a fasting plasma glucose of 126 mg/dL or greater hemoglobin A1C (HbA1C) 6.5% or above or the use of anti-diabetic medication
4. The use of nitrates.
5. The metabolism of galantamine is primarily through the cytochrome P450 system, specifically the CYP2D6 and CYP3A4 isoenzymes. We will exclude subjects who have impaired hepatic function and/or who are currently using strong inhibitors of CYP3A4 and CYP2D6 (e.g. ketoconazole and paroxetine, respectively).
6. Pregnancy or breast-feeding. Women of child-bearing potential will be required to have undergone tubal ligation or to be using an oral contraceptive or barrier methods of birth control.
7. Post-menopausal women.
8. The use of any other central or peripheral acetylcholinesterase inhibitor (donezepil (Aricept(R)), pyridostigmine (Mestinon(R)), rivastigmine (Exelon(R)), tacrine (Cognex(R)).
9. First, second or third-degree AV block detected during the screening visit with an ECG
10. Seizures or history of seizures.
11. Current smokers defined as those who smoked a cigarette in the last 30 days.
12. History of recurrent syncope.
13. History of serious neurologic disease such as cerebral hemorrhage, stroke, or transient ischemic attack.
14. History of cardiac shunts.
15. Allergy to eggs or soy.
16. Impaired hepatic function (aspartate amino transaminase \[AST\] and/or alanine amino transaminase \[ALT\] \>3.0 x upper limit of normal range)
17. Impaired renal function test (eGFR\<60 mL/min/1.73m2)
18. Anemia (hematocrit \<34%)
19. Ongoing substance abuse.
20. Treatment with any investigational drug in the one month preceding the study
21. Mental conditions rendering a subject unable to understand the nature, scope and possible consequences of the study
22. Inability to comply with the protocol, e.g. uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study

Where this trial is running

Nashville, Tennessee

• Chaney Johnson — Nashville, Tennessee, United States (Recruiting)

Study contacts

• Principal investigator: Cyndya Shibao, MD — Vanderbilt University Medical Center
• Study coordinator: Cyndya Shibao, MD

Conditions Endothelial Dysfunction; African American; Flow-mediated dilation; Vascular Oxidative Stress