Valacyclovir + Shingrix for Achalasia

Overseen By Michael McGill, BS

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Vanderbilt University Medical Center

Must be taking: Valacyclovir, Shingrix

Disqualifiers: Unstable illness, Neurologic impairment, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 4 months

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether treating a chronic varicella zoster virus (VZV) infection can aid individuals with achalasia, a condition that makes swallowing difficult. The treatment involves taking valacyclovir, an antiviral medication, and possibly receiving the Shingrix vaccine, a recombinant varicella zoster virus vaccine. The trial aims to determine if the virus contributes to the swallowing problem and to understand the role of nerve cells and mast cells (a type of immune cell) in this process. Individuals diagnosed with achalasia and who have VZV DNA in their saliva might be suitable candidates for this trial. As a Phase 4 trial, this research involves an FDA-approved treatment and seeks to understand how it benefits more patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it mentions that patients with well-controlled conditions like hypertension and diabetes can participate, suggesting that some medications might be allowed.

What is the safety track record for Shingrix and Valacyclovir?

Research has shown that both Valacyclovir and Shingrix are generally well-tolerated. Valacyclovir, commonly used to treat viral infections like herpes, is absorbed well by the body and maintains a steady level. While specific safety information for Valacyclovir in treating achalasia is lacking, it is known to be safe for other conditions.

Shingrix, a vaccine that prevents shingles, is particularly effective for people over 50. Studies indicate it is over 90% effective in preventing shingles. Any side effects, such as mild reactions at the injection site, typically occur within a day of vaccination. With Shingrix already approved for preventing shingles, it has a strong safety record.

Overall, the widespread use of both treatments for other conditions provides reassurance about their safety. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for achalasia, which often involve surgical procedures or pneumatic dilation, this approach combines valacyclovir and the Shingrix vaccine. Researchers are excited about these treatments because valacyclovir targets the Varicella Zoster Virus (VZV) DNA found in saliva, offering a unique antiviral angle that is not typical in current achalasia treatments. Additionally, Shingrix, a vaccine typically used for shingles, may boost the immune response to further alleviate symptoms. This combination provides a novel, less invasive alternative that could potentially benefit patients with specific virus-related achalasia phenotypes.

What evidence suggests that Valacyclovir and Shingrix might be effective treatments for achalasia?

Research has shown that a long-lasting infection of the varicella zoster virus (VZV), which usually causes chickenpox and shingles, links to achalasia. Achalasia makes swallowing difficult because the passage between the esophagus and stomach doesn't work properly. This trial studies Valacyclovir, a medication used to treat shingles, to determine if it can reduce achalasia symptoms by targeting this virus. Studies have demonstrated that valacyclovir effectively fights VZV infections. Participants who benefit from valacyclovir treatment will receive Shingrix, a vaccine known for successfully preventing shingles by boosting the body's immune response to VZV. The combination of valacyclovir and Shingrix aims to address the virus from both treatment and prevention angles, potentially reducing achalasia symptoms. ^{1 2 4 5 6}

Who Is on the Research Team?

Michael Vaezi, MD

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

This trial is for men and women aged 18-75 with achalasia, a condition that makes swallowing difficult. Participants must be fluent in English, able to give consent, and undergo specific diagnostic tests. Women of childbearing age should use effective birth control.

Inclusion Criteria

Fluent in English and mentally capable to provide informed consent who present to Vanderbilt University Medical Center Digestive Diseases Center for treatment of achalasia

I have been diagnosed with achalasia and am fit for treatment.

I can undergo specific swallowing tests, a nasal procedure for esophagus testing, and follow a 2-month treatment plan including medication and vaccinations.

Exclusion Criteria

My chronic conditions like high blood pressure or diabetes are well-managed.

I do not have any brain or thinking problems that would stop me from joining a study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients with Achalasia (phenotypes II and III) with VZV DNA in saliva are treated with valacyclovir 3 times per day

4 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including response to anti-VZV therapy and incidence of VZV reactivation

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Shingrix
• ValACYclovir 1000 MG

Trial Overview The study aims to treat achalasia by targeting the varicella zoster virus (VZV), which may cause it. It involves taking ValACYclovir pills three times daily and receiving two Shingrix injections over two months.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 2 Interventions

Patients with Achalasia (phenotypes II and III) with VZV DNA in saliva. Patients will be treated with valacyclovir 3 times per day. Patients found to benefit from treatment with valacyclovir will be offered Shingrix vaccine (2 - 0.5mL doses)

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

Approved in United States as Shingrix for:

• Prevention of shingles in healthy adults over age 50 and in immunocompromised adults over age 18

Approved in European Union as Shingrix for:

• Prevention of herpes zoster (shingles) and postherpetic neuralgia (PHN) in adults 50 years of age and older

Approved in Canada as Shingrix for:

• Prevention of herpes zoster (shingles) in adults 50 years of age and older

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Columbia University

Collaborator

Trials

1,529

Recruited

2,832,000+

Published Research Related to This Trial

Shingrix is a new vaccine designed to prevent herpes zoster, commonly known as shingles, which can cause painful rashes and complications.

Clinical trials have shown that Shingrix is highly effective in reducing the incidence of shingles in adults, particularly in older populations, making it a significant advancement in herpes zoster prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Shingrix: A New Herpes Zoster Vaccine. Maltz, F., Fidler, B.[2020]

Shingrix is an approved vaccine in Germany for preventing shingles (zoster) and its complications, specifically for adults aged 60 and older.

If patients experience bullous skin lesions after receiving Shingrix, it is important to consider the possibility of zoster disease and report any unexpected side effects to the appropriate medical authorities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Zoster disease after Shingrix vaccination]. Kohn, D., Wetzig, T.[2021]

In a study of Medicare beneficiaries aged over 65, Shingrix demonstrated a vaccine effectiveness of 70.1% for those receiving the full 2-dose regimen and 56.9% for those receiving only 1 dose, indicating that completing the 2-dose series is beneficial.

The vaccine remained effective even for individuals over 80 years old and those with autoimmune or immunosuppressive conditions, with a notable 76.0% effectiveness against postherpetic neuralgia, suggesting its broad applicability in older and at-risk populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant Zoster Vaccine (Shingrix): Real-World Effectiveness in the First 2 Years Post-Licensure. Izurieta, HS., Wu, X., Forshee, R., et al.[2022]

SHINGRIX, a non-live herpes zoster vaccine, is safe for patients on immunosuppressive therapy, making it a suitable option for those with inflammatory bowel disease who are at higher risk for infections.

A case report of a 74-year-old woman with ulcerative proctosigmoiditis revealed blistering autoimmune skin disorders following SHINGRIX vaccination, suggesting a potential, though previously unreported, adverse effect of the vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blistering autoimmune skin reaction following SHINGRIX vaccination in an ulcerative colitis patient: Case report and literature review. Bell, H., Kamal, N., Wong, U.[2021]

Shingrix® is a highly effective recombinant zoster vaccine that significantly reduces the risk of herpes zoster (HZ) and postherpetic neuralgia (PHN) in adults aged 50 and older, with efficacy remaining strong even after 4 years.

While Shingrix® is associated with more side effects than a placebo, such as injection-site reactions and fatigue, these reactions are generally mild to moderate and transient, making it a well-tolerated option for preventing HZ and PHN.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant Zoster Vaccine (Shingrix®): A Review in Herpes Zoster. Syed, YY.[2022]

Citations

1. shingrixhcp.com shingrixhcp.com/efficacy-safety/efficacy-data/

SHINGRIX (Zoster Vaccine Recombinant, Adjuvanted) SHINGRIX is a vaccine indicated for prevention of herpes zoster (HZ) (shingles): ... SHINGRIX is not indicated for prevention of primary varicella infection ( ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12001543/

A fresh look at varicella vaccination - PMC Varicella zoster virus (VZV) is one of the 8 herpesviruses that infect humans. Other human herpesviruses include the herpes simplex viruses (HSV) ...

3. withpower.com withpower.com/trial/phase-4-esophageal-achalasia-11-2022-1f897

Valacyclovir + Shingrix for Achalasia Varicella zoster virus (VZV) is the cause of chickenpox and shingles, but it ... Recombinant Zoster Vaccine (Shingrix®): A Review in Herpes Zoster.

4. vanderbilt.trialstoday.org vanderbilt.trialstoday.org/trial/NCT05550194

VZV in the Enteric Nervous System Varicella zoster virus (VZV) is the cause of chickenpox and shingles, but it also infects, becomes latent, and reactivates in nerve cells of the ...

5. go.drugbank.com go.drugbank.com/drugs/DB13924

Varicella zoster vaccine (recombinant) - Shingrix Herpes zoster, also known as shingles, is caused by a reactivation of Varicella Zoster Virus (VZV), the virus that commonly causes Chickenpox in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11788766/

Post-marketing safety surveillance for the recombinant zoster ... The median time-to-onset for adverse events of recombinant zoster vaccine was 1 day. •. Eighty-six deaths were reported following recombinant ...