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

Part of paid clinical trials in Nashville, Tennessee.

Sponsor
Vanderbilt University Medical Center
Study ID
NCT04769206
Phase
PHASE1/PHASE2
Status
Recruiting
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Conditions

  • Endothelial Dysfunction

Eligibility Criteria

Sex
ALL
Age
18 Years - 60 Years
Healthy Volunteers
Accepted

Interventions

  • Galantamine — DRUG
    4mg daily titrating up to 8mg twice a day
  • Placebo — DRUG
    1 pill a day for 4 weeks, 2 pills a day for 8 weeks
  • TENS 7000 — DEVICE
    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.

Study Details

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.

Key Dates

Start date
Dec 20, 2021
Status verified
May 2026
Primary completion
May 31, 2027
Completion
Jun 1, 2028

Study Design

Enrollment
160 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

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

Primary Outcome Measure

FMD [ Time Frame: From baseline to 3 months ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
Chaney JohnsonNashvilleTennessee37232
Chaney Johnson
[email protected]
Cyndya A Shibao, MD (PRINCIPAL_INVESTIGATOR)
Annet Kirabo, DVM PHD (SUB_INVESTIGATOR)

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