VZV in the Enteric Nervous System: Pathogenesis and Consequences

NCT05550194 | Recruiting Phase 4 FDA Drug

• 1 other identifier: VENS_220945
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Varicella zoster virus (VZV) is the cause of chickenpox and shingles, but it also infects, becomes latent, and reactivates in nerve cells of the bowel to cause a gastrointestinal disorder ("enteric shingles"). The Investigators recently found that a chronic active VZV infection, a form of enteric shingles, is associated with achalasia, a severe disease in which the passage of food from esophagus to stomach is impaired. We now propose to eradicate VZV to determine whether its association with achalasia is causal, to identify the genetic basis behind VZV reactivation in the esophagus, and the relationship of mast cells to enteric shingles and abdominal pain.

Conditions

Achalasia

Outcome Measures

Primary Outcomes (1)

• Response of VZV-associated achalasia to anti-VZV therapy.

  Response will be measured by the Eckardt score. The Eckardt score is the sum of the symptom scores for dysphagia, regurgitation, and chest pain (with a score of 0 indicating the absence of symptoms, 1 indicating occasional symptoms, 2 indicating daily symptoms, and 3 indicating symptoms at each meal) and weight loss (with 0 indicating no weight loss, 1 indicating a loss of \<5 kg, 2 indicating a loss of 5 to 10 kg, and 3 indicating a loss of \>10 kg).

  4 months

Secondary Outcomes (3)

• Difference in viral loads in achalasia phenotype II versus phenotype III

  One year

• Genetic typing of reactivation of VZV in the esophagus

  One year

• Incidence of reactivation of VZV due to mast cell degranulation

  One year

Study Arms (1)

Treatment

EXPERIMENTAL

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)

Drug: ValACYclovir 1000 MG; Biological: Shingrix

Interventions

ValACYclovir 1000 MG DRUG

Valacyclcovir is a targeted anti-viral for varicella zoster virus (VZV).

Also known as: Valtrex

Treatment

Shingrix BIOLOGICAL

Vaccine indicated for prevention of herpes zoster

Also known as: Zoster vaccine recombinant

Treatment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female subjects aged 18-75 years old inclusive (females of childbearing potential should be on highly effective contraceptive methods)
• Fluent in English and mentally capable to provide informed consent who present to Vanderbilt University Medical Center Digestive Diseases Center for treatment of achalasia.
• Based on standard clinical practice, we anticipate that patients who undergo these treatments will have been formally diagnosed with achalasia and will be fit to undergo the selected treatment intervention.
• All subjects must be able to undergo timed barium swallow testing, trans-nasal intubation for high-resolution manometry probe, and therapeutic intervention of a 2-month course of valacyclovir 1g TID and two injections of Shingrix over a two-month period.

You may not qualify if:

• Unstable medical illness with ongoing diagnostic work-up and treatment. Patients with well-controlled hypertension, diabetes and a remote history of ischemic heart disease that is deemed stable, as judged by the physician-investigator can be included.
• Current neurologic or cognitive impairment which would make the patient an unsuitable candidate for a research trial.

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• Columbia University: collaborator

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37129, United States

RECRUITING

MeSH Terms

Conditions

Esophageal Achalasia

Interventions

Valacyclovir

Condition Hierarchy (Ancestors)

Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Michael Vaezi, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michael McGill, BS

CONTACT

6153224643; michael.g.mcgill@vumc.org

Amy Motley, BS

CONTACT

6153226281; amy.motley@vumc.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine, Gastroenterology, Hepatology, and Nutrition

Model Details: Patients with Achalasia (phenotypes II and III) with VZV DNA in saliva

Study Record Dates

• First Submitted: September 19, 2022
• First Posted: September 22, 2022
• Study Start: March 27, 2023
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: May 16, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

US (1)