Using Oral Valacyclovir to Treat Patients With Refractory IC/BPS (VARIC)

Urology Department, Hualien Tzu Chi Hospital, Hualien, Taiwan

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a collective term referring to disorders which is characterized by lower urinary tract symptoms, including bladder pain/discomfort, frequent urination without evidence of bacterial infection. The etiology of IC/BPS is still uncertain, and most current treatment for IC/BPS are only symptoms control. Our previous study revealed Epstein-Barr virus (EBV) infection presented in the IC/BPS bladders and involved the pathogenesis. Hence, using anti-viral medication valacyclovir for the patients with IC/BPS might have clinical efficacy.

Study Overview

• Status: Recruiting
• Conditions: Quality of Life; Pain, Chronic; Urge Incontinence; Overactive Bladder Syndrome
• Intervention / Treatment: Drug: Valacyclovir

Detailed Description

We would like to conduct a prospective study to evaluate to therapeutic effect of oral valacyclovir for the patients with IC/BPS. The diagnosis of IC/BPS was made through following the clinical symptom index of the American Urological Association guideline. The IC/BPS patients with concurrent urological diseases, such as neurogenic voiding dysfunction, ketamine cystitis or acute bacterial cystitis in recent one month would be excluded. The IC/BPS patients with possibility of pregnancy also would be rule out.

At first, the enrolled patients would be investigated for urinary analysis and culture to rule out current bacteriuria. The enrolled patients would receive a comprehensive medical history review. A pregnancy test would be performed for women of childbearing potential. The patients would be asked to provide urine sample to urinary virus investigation before the treatment. The IC/BPS patients would be investigated for baseline clinical symptoms questionnaire including VAS, QoL, ICPI, ICSI, and OSS. The parameters in the VUDS report also would be record. The Informed consent would be obtained from all individual participants before the intervention. Due to higher bioavailability, we would use valacyclovir in this study. The dose of valacyclovir we use is according to previous valacyclovir study for genital HSV infection. [18] According previous valacyclovir study for chronic recurrence herpesvirus infection disease, long-term therapy of oral valacyclovir < 1000mg/day should be effective and safe; the safety profiles of valacyclovir and placebo were similar. All of our patients would receive open-label oral valacyclovir 500 mg twice per day for 4 weeks.

We estimate to enroll 30 IC/BPS patients with evidence of EBV infection in bladder into this study. After the beginning of valacyclovir therapy, the patients would receive a telephone interview to evaluated current symptoms changes at first and second weeks. The overall improvement of current therapy would be assessed with Global Response Assessment (GRA) (3: symptoms free, 2: >50% symptoms improvement, 1: 25-50% symptoms improvement, 0: 0-25% symptoms improvement, -1: symptoms worse). The GRA, VAS, and any adverse effect would be investigated in the telephone interview. After the full 4 weeks treatment, the patients would be asked to back to our clinic. All symptoms questionnaire (GRA, VAS, QoL, ICPI, ICSI, and OSS) and adverse effect would be evaluated again. The patients would be asked to provide urine sample again. The primary endpoint of this study is the GRA at 4 weeks. The secondary endpoints include the changes of VAS, VAS, QoL, ICPI, ICSI, and OSS between baseline and end of the study. The following figure showed the study flow diagram.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• Taiwan
  • Hualien City, Taiwan, 970
    • Recruiting
    • Hualien Tzu Chi Hospital
    • Contact: Hann-Chorng Kuo, M.D.; Phone Number: 2117 886-3-856-1825; Email: Hck@tzuchi.com.tw
    • Contact: Jia-Fong Jhang, M.D.; Phone Number: +886916958785; Email: alur1984@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• patients with IC/BPS

Exclusion Criteria:

• patients with neurogenic bladder
• patients with bladder outlet obstruction
• patients with lymphoma
• patients with bacteria cystitis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Global Response Assessment (GRA)	3: symptoms free, 2: >50% symptoms improvement, 1: 25-50% symptoms improvement, 0: 0-25% symptoms improvement, -1: symptoms worse	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
VAS	VAS scale for pain	1 month
OSS	O'Leary-Sant Symptom Index	1 month

Collaborators and Investigators

• Sponsor: Buddhist Tzu Chi General Hospital
• Collaborators: Ministry of Science and Technology, Taiwan; Hualien Tzu Chi General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2021
• Primary Completion (Anticipated): February 28, 2022
• Study Completion (Anticipated): April 30, 2022

Study Registration Dates

• First Submitted: October 14, 2021
• First Submitted That Met QC Criteria: October 14, 2021
• First Posted (Actual): October 26, 2021

Study Record Updates

• Last Update Posted (Actual): October 26, 2021
• Last Update Submitted That Met QC Criteria: October 14, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Urinary Bladder Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Pain; Neurologic Manifestations; Urination Disorders; Urinary Incontinence; Urinary Bladder, Overactive; Chronic Pain; Urinary Incontinence, Urge; Anti-Infective Agents; Antiviral Agents; Valacyclovir
• Other Study ID Numbers: MOST 109 2314 B 303 024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No