Galantamine for Endothelial Dysfunction

Recruiting at 1 trial location

Overseen By Annet Kirabo, DVM PHD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Vanderbilt University Medical Center

Must not be taking: Nitrates, CYP3A4 inhibitors

Disqualifiers: Heart disease, Hypertension, Diabetes, Seizures, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 10

Duration: 12 weeks

88 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether the drug galantamine can improve blood vessel health and reduce stress markers in African Americans. Researchers aim to determine if taking galantamine for three months enhances blood vessel function and reduces harmful protein formations that can lead to heart problems. Participants may also try a device that stimulates nerves to assess its impact on blood vessel health. Ideal participants are African American adults with a BMI over 28, who have not experienced major heart or stroke events and are not managing diabetes or uncontrolled hypertension. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as nitrates, strong inhibitors of CYP3A4 and CYP2D6 (like ketoconazole and paroxetine), and any other central or peripheral acetylcholinesterase inhibitors. If you are on these medications, you would need to stop them to participate in the trial.

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

Research has shown that galantamine has been tested for safety in humans, primarily for treating Alzheimer's disease. In earlier studies, some participants experienced side effects such as nausea, stomach pain, and vomiting. These side effects, mostly related to digestion, occur more frequently at higher doses.

Although these side effects can be uncomfortable, they are usually not dangerous. The treatment is generally well-tolerated, especially when the dose is gradually increased to help the body adjust. However, more research is needed to fully understand the safety of galantamine for treating other conditions, such as vascular issues.

Prospective trial participants should be aware of these possible side effects and discuss any concerns with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike standard treatments for endothelial dysfunction that typically focus on lowering blood pressure or cholesterol, Galantamine offers a unique approach by potentially improving vascular function through its action on the nervous system. Galantamine works by enhancing the activity of the vagus nerve, which may help reduce inflammation and oxidative stress in blood vessels. Researchers are excited about Galantamine because it targets the nervous system's regulation of vascular health, offering a novel mechanism that could complement existing therapies and provide additional benefits for patients with endothelial dysfunction.

What evidence suggests that galantamine might be an effective treatment for endothelial dysfunction?

This trial will evaluate the effects of Galantamine on endothelial dysfunction. Research has shown that Galantamine can help treat Alzheimer's disease and vascular dementia by enhancing certain body functions that improve blood vessel performance. While scientists continue to study its effects on blood vessel issues, Galantamine has improved memory and thinking in related conditions. It may also help reduce stress and inflammation, which are linked to blood vessel problems. These early findings suggest it might be useful for treating blood vessel issues. Participants in this trial may receive Galantamine, while others will receive a placebo for comparison. ^{6 7 8 9 10}

Who Is on the Research Team?

Cyndya A Shibao, MD

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

This trial is for African American men and women aged 18 to 60 with a BMI over 28. It's not suitable for those with liver or kidney issues, anemia, diabetes, certain medication use, pregnancy, substance abuse, uncontrolled hypertension, serious heart conditions or neurologic diseases.

Inclusion Criteria

I am an African American woman or man.

You have a body mass index (BMI) higher than 28, which means you are overweight.

Exclusion Criteria

My blood pressure is often above 140/90 despite taking medication.

I use nitrates for my condition.

You have taken any experimental medication within the month before the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Randomization and Initial Assessment

Participants undergo initial assessments including EKG, blood tests, and are randomized to treatment or placebo

1 day

1 visit (in-person)

Treatment

Participants receive galantamine or placebo for 3 months with dose titration and telemedicine follow-ups

12 weeks

3 visits (in-person), 3 visits (telemedicine)

Safety Follow-up

Participants attend outpatient clinic visits for safety monitoring and dose titration

8 weeks

3 visits (in-person)

Final Assessment

Final assessment of endpoints including repeated procedures from initial assessment

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Sub-study (Optional)

Evaluation of trans-auricular vagus nerve stimulation effects on vascular oxidative stress

1 day

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Galantamine
• Placebo

Trial Overview

The study tests if galantamine can reduce oxidative stress and improve endothelial function in African Americans over three months. Participants will be compared to a placebo group to see if there are changes in blood markers and vascular reactivity.

How Is the Trial Designed?

Group I: Galantamine Experimental Treatment 1 Intervention

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

Group II: TENS 7000 Active Control 1 Intervention

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

Group III: Placebo Placebo Group 1 Intervention

placebo (micro crystalline cellulose) \- 1 pill once daily for 4 weeks, then 2 pills daily for 8 weeks

Galantamine is already approved in United States, European Union for the following indications:

Approved in United States as Razadyne for:

• Mild to moderate dementia associated with Alzheimer's Disease

Approved in European Union as Reminyl for:

• Mild to moderate dementia associated with Alzheimer's Disease

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Published Research Related to This Trial

Galantamine, an acetylcholinesterase inhibitor, has shown significant cognitive and global benefits in patients with Alzheimer's disease, particularly at daily doses of 24-32 mg over treatment durations of 3 to 6 months, based on a review of seven trials involving various durations and doses.

While galantamine is effective, it has gastrointestinal side effects similar to other cholinesterase inhibitors, and higher doses (32 mg/day) may lead to higher discontinuation rates, although a slower titration can mitigate this risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Galantamine for Alzheimer's disease. Olin, J., Schneider, L.[2018]

In a 12-week study involving 82 Alzheimer's patients, a 1-week dose titration of extended-release galantamine (GAL-ER) was found to be generally safe and well tolerated, although there was a higher incidence of gastrointestinal side effects compared to a longer titration period.

Patients showed a slight improvement in cognitive function, with Mini-Mental State Examination scores increasing by 1.8 points at week 4 and 1.9 points at week 12, suggesting that the 1-week titration could help with medication adherence while managing safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

One-week dose titration of extended release galantamine in patients with Alzheimer's disease. Scharre, DW., Shiovitz, T., Zhu, Y., et al.[2013]

Galantamine has shown significant efficacy in improving cognitive function and global ratings in patients with Alzheimer's disease, particularly at doses of 16-32 mg over treatment durations of 3 to 6 months, based on a review of seven trials involving a total of 7460 participants.

The safety profile of galantamine is similar to other cholinesterase inhibitors, with gastrointestinal symptoms being the most common side effects, and a dose of 16 mg/day appears to be the best tolerated, suggesting it may be the preferred starting dose for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Galantamine for Alzheimer's disease. Olin, J., Schneider, L.[2020]

Galantamine, an acetylcholinesterase inhibitor, has shown significant efficacy in improving cognitive function and global ratings in patients with Alzheimer's disease, particularly at doses of 16-32 mg/day over treatment durations of 3 to 6 months, based on a systematic review of 7 trials involving a total of several hundred participants.

The safety profile of galantamine is similar to other cholinesterase inhibitors, with gastrointestinal side effects being the most common, and a dose of 16 mg/day appears to be the best tolerated, making it a preferable starting dose for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Galantamine for Alzheimer's disease. Olin, J., Schneider, L.[2020]

Galantamine and its derivatives show significant antioxidant and neuroprotective effects by reducing oxidative stress, which is linked to various diseases, including Alzheimer's and Parkinson's.

The mechanisms of action include scavenging reactive oxygen species, preventing mitochondrial damage, and enhancing acetylcholine levels, which together help protect neurons from cytotoxic agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antioxidant activity of galantamine and some of its derivatives. Tsvetkova, D., Obreshkova, D., Zheleva-Dimitrova, D., et al.[2019]

In a study involving 788 patients with vascular dementia, galantamine significantly improved cognitive function compared to placebo after 26 weeks, as measured by the ADAS-cog/11 scale.

While galantamine showed benefits in cognition and executive function, it did not demonstrate a significant improvement in daily living activities compared to placebo, indicating that while it is effective for cognitive symptoms, its impact on overall daily functioning may be limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Galantamine treatment of vascular dementia: a randomized trial. Auchus, AP., Brashear, HR., Salloway, S., et al.[2022]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04769206

Enhancing Parasympathetic Activity to Improve Endothelial ...

Specific Aim 2: To determine if prolonged (3-month) treatment with galantamine improves endothelial dysfunction as measured by vascular reactivity in AAs.

2.

reporter.nih.gov

reporter.nih.gov/search/pfLrj9qkC0-AThH8VAsVgA/project-details/10625349

Project Details

The overall goal of the current proposal is to determine if prolonged treatment with galantamine improves endothelial dysfunction and vascular oxidative stress ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12150971/

Rapid health technology assessment of galantamine for ...

Galantamine showed good efficacy, cost-effectiveness, and mild adverse effects in the treatment of patients with AD by prolonging the duration of full-time ...

4.

go.drugbank.com

go.drugbank.com/drugs/DB00674

Galantamine: Uses, Interactions, Mechanism of Action

Galantamine exhibited therapeutic efficacy in studies of vascular dementia and Alzheimer's disease with cerebrovascular disease. In one study, galantamine ...

5.

researchgate.net

researchgate.net/publication/7337127_Galantamine_for_vascular_cognitive_impairment

Galantamine for vascular cognitive impairment

Galantamine has been shown to be effective in patients with AD [14]. The effects in VCI, however, have been inconsistent [15] . In the STREAM- ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8406621/

Galantamine for vascular cognitive impairment - PMC

In both included trials galantamine produced higher rates of gastrointestinal side‐effects. More studies are needed before firm conclusions can be drawn.

7.

journals.lww.com

journals.lww.com/md-journal/fulltext/2024/04190/evaluating_the_efficacy_and_safety_of_alzheimer_s.55.aspx

Evaluating the efficacy and safety of Alzheimer's disease...

The aim of this study is to quantitatively evaluate the efficacy and safety of cholinesterase inhibitors (ChEIs), memantine, and sodium oligomannate (GV-971) ...

8.

nature.com

nature.com/articles/s41392-024-01911-3

Recent advances in Alzheimer's disease: mechanisms ...

A phase III clinical trial (NCT04669028) has been completed, aimed at testing the safety and efficacy of the drug in elderly patients with mild ...

9.

sciencedirect.com

sciencedirect.com/science/article/pii/S0168365924000622

Alzheimer's disease current therapies, novel drug delivery ...

The gastrointestinal related side effects with galantamine therapy are nausea, cramping, salivation, and vomiting. However, the other effects are ...

10.

clinicaltrials.gov

clinicaltrials.gov/study/NCT00261573

NCT00261573 | A Study of the Safety and Effectiveness ...

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical ...