Recruiting
Phase 1
Phase 2

Parasympathetic Activity

Sponsor:

Vanderbilt University Medical Center

Code:

NCT04769206

Conditions

Endothelial Dysfunction

Eligibility Criteria

Sex: All

Age: 18 - 60

Healthy Volunteers: Accepted

Interventions

Galantamine

Placebo

TENS 7000

Study Details

Brief summary:

Specific Aim 1: To test the hypothesis that prolonged (3-month) treatment with galantamine inhibits NADPH IsoLG-protein adducts formation and improves markers of endothelial cell (EC) dysfunction in AAs.

Aim 1a: The investigators will determine if galantamine inhibits NADPH IsoLG-protein adducts formation, superoxide production, and immune cell activation compared to placebo.

For this purpose, the investigators will study peripheral blood mononuclear cell (PBMC), a critical source of systemic oxidative stress, collected from study participants.

Aim 1b: The investigators will determine if galantamine reduces intracellular Iso-LGs, ICAM-1, and 3-nitrotyrosine, a marker of vascular oxidative stress, in ECs harvested from study participants.

Specific Aim 2: To determine if prolonged (3-month) treatment with galantamine improves endothelial dysfunction as measured by vascular reactivity in AAs. The investigators will measure vascular reactivity in response to ischemia in two vascular beds: (a) in conduit arteries (brachial artery) using brachial artery diameter flow-mediated dilation (FMD), and (b) in the microvasculature (MBV) using contrast-enhanced ultrasonography in skeletal muscle.

Sub-study (optional) Will study the effect of trans-auricular vagus nerve stimulation (TaVNS) during a period of enhanced vascular oxidative stress

This proposal will study a novel mechanism that could alter the oxidative and immunogenic responses that contributes to endothelial dysfunction in AAs and will offer a potential pathway for the development of more effective therapies aimed at decreasing the progression of endothelial dysfunction to cardiovascular disease in this population.

Conditions

Endothelial Dysfunction

Study ID

NCT04769206

Start date

Dec 20, 2021

Status verified date

May, 2026

Completion date

Jun 1, 2028

Anticipated

Primary completion date

May 31, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 60

Healthy Volunteers: Accepted

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

Study Design

Enrollment

160 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Galantamine

Galantamine 16mg/day

\- titrating: 4mg once a day for 2 weeks, titrate to 8mg once a day for 2 weeks, then 8mg twice a day for 8 more weeks

placebo comparator: Placebo

placebo (micro crystalline cellulose)

\- 1 pill once daily for 4 weeks, then 2 pills daily for 8 weeks

active comparator: TENS 7000

Substudy: the effect of trans-auricular vagus nerve stimulation (TaVNS) will be done by FDA-approved TENS 7000 device and during a period of enhanced vascular oxidative stress

Interventions

Galantamine

4mg daily titrating up to 8mg twice a day

Placebo

1 pill a day for 4 weeks, 2 pills a day for 8 weeks

TENS 7000

The FDA-approved TENS 7000 device will be used for Trans-auricular vagus nerve stimulation (TaVNS) during a period of enhanced vascular oxidative stress. This device will be supplemented with ear clip electrodes. The site of the stimulation for such electrodes are the tragus or concha. The device will have built in safety controls to minimize additional risks to the subjects (as per FDA guidance on stimulators). We will use typical stimulation conditions (30 Hz, 300 µs) and amplitude dependent on perception threshold.

Primary outcome measure

  • FMD [ Time Frame: From baseline to 3 months ]
  • NADPH activation in PBMC [ Time Frame: From baseline to 3 months ]
  • NADPH activation in PBMC at TaVNS stimulation [ Time Frame: From baseline to 120 minutes to 240 minutes ]

Central Contacts and Locations

Central contacts

Locations

Chaney Johnson

Recruiting

Nashville, Tennessee, United States, 37232

Contacts

Principal Investigator:

Cyndya A Shibao, MD

More Information

Sponsor

Vanderbilt University Medical Center

Last update posted

May 18, 2026

Last verified

May, 2026

Keywords

  • African American
  • Flow-mediated dilation (FMD)
  • Vascular Oxidative Stress

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Vanderbilt University Medical Center on 2026-05-18.