A Pilot Open-Label Prospective Study of Safety and Preliminary Efficacy of Endoscopic Submucosal Injection of Hyaluronic Acid Into the Bladder Wall in Patients With Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) (HA-IC/BPSPilot)

June 14, 2026 updated by: Sverdlovsk Regional Clinical Hospital No.1

The goal of this pilot clinical trial is to learn if injecting hyaluronic acid into the bladder wall is safe and if it works to reduce pain and urinary frequency in people with interstitial cystitis (IC), also called bladder pain syndrome (BPS).

Who can take part? Adults aged 18 and older who have IC/BPS that did not get better after at least two standard treatments (such as diet changes, oral drugs, or bladder instillations) for 6 months or more.

Main questions the study aims to answer:

What side effects (medical problems) do participants have after the injection procedure?

Does the injection lower pain and reduce how often a person needs to urinate, compared to before the treatment?

What will happen in the study? There is no comparison group or placebo (a look-alike substance with no drug). All participants receive the same treatment.

Participants will:

Have a one-time procedure under intravenous anesthesia (medicine that puts them to sleep)

Receive 20 small injections of hyaluronic acid into the bladder wall using a thin tube with a camera (cystoscope)

Have small tissue samples taken from the bladder (biopsy) during the same procedure

Keep a 3-day diary of their urination

Fill out short questionnaires about pain, symptoms, and quality of life

Return for follow-up visits at 1 day, 1 week, 4 weeks, 3 and 6 months after the injection.

At the 4-week visit, participants will have cystoscopy with bladder biopsy and may receive a second injection if the first one helped.

Possible benefits We cannot guarantee that this experimental treatment will help everyone. However, based on years of experience with similar hyaluronic acid injections in other body parts, researchers hope that injecting the substance directly into the bladder wall will give longer-lasting relief than standard bladder instillations.

Risks and side effects

The most common expected side effects are:

Blood in the urine for a few hours or days (usually goes away on its own) Temporary increase in pain or burning when urinating Infection (unlikely; the team will give antibiotics to lower the risk) Serious problems such as bladder wall puncture or allergic reaction are very rare.

Participation is voluntary People can join or leave the study at any time without giving a reason. Refusing or stopping will not affect their regular medical care at the hospital.

Confidentiality All personal information will be kept private. Results will only be shared in combined, anonymous form (no names or identifying details).

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Study design in detail This is a prospective, open-label, single-center, pilot phase I-II clinical trial. No randomization or blinding is applied. All enrolled participants receive the same intervention. The study aims to enroll 10-20 evaluable participants with refractory interstitial cystitis/bladder pain syndrome (IC/BPS).

Rationale for submucosal injection of non-cross-linked hyaluronic acid Hyaluronic acid (HA) is a natural component of the extracellular matrix. Intravesical HA instillations are a standard therapy for IC/BPS but require frequent administration (up to 3 times per week for ≥6 months) and provide only temporary relief in many patients. Submucosal injection is hypothesized to achieve a higher and more prolonged local concentration of HA in the lamina propria, enhancing glycosaminoglycan layer repair, reducing inflammation, and stimulating fibroblast activity and neocollagenesis. This technique is technically identical to endoscopic botulinum toxin injection, which has an established safety profile in the bladder.

Extrapolated safety evidence

The safety of submucosal non-cross-linked HA injection is supported by extensive experience in other mucosal sites:

Laryngoplasty (vocal cords): no serious adverse events (SAEs) in published case series; histological evidence of biocompatibility without chronic inflammation or necrosis.

Vulvovaginal atrophy and provoked vestibulodynia: randomized and retrospective studies show only transient edema and pain (10-25%), no SAEs.

Non-surgical rhinoplasty: serious complication rate <0.05% with proper technique.

Endoscopic treatment of vesicoureteral reflux (VUR): >20 years of experience with dextranomer/hyaluronic acid copolymer (Deflux®) in >2500 patients - obstruction requiring intervention occurs in <1% of ureters; long-term follow-up (≥10 years) shows no malignancy or delayed tissue damage.

Intervention details

Device: Flexible or rigid cystoscope.

Injection needle: 23-25 Gauge, length 4 mm (standard endoscopic injection needle).

Product: Non-cross-linked hyaluronic acid (marketing authorization No. РЗН 2024/22715, Russian Federation). Each milliliter contains 10 mg of sodium hyaluronate.

Injection protocol: 20 submucosal injections of 0.5 mL each, evenly distributed over the bladder wall (trigone avoided). Total volume injected = 10 mL.

Anesthesia: Intravenous general anesthesia.

Post-procedure care: No indwelling catheter. Single dose of perioperative antibiotic (cephalosporin) for infection prophylaxis.

Optional repeat procedure Participants who show a positive clinical response (e.g., ≥2-point reduction in VAS pain score at week 4) may be offered a second identical injection at the week-4 visit (V4). This decision is made jointly by the investigator and the participant.

Histological and endoscopic evaluation

At baseline (V1) and at week 4 (V4, before optional repeat injection), punch biopsies are taken from predetermined sites (e.g., posterior wall, lateral wall). Tissue samples are fixed in formalin and stained with hematoxylin and eosin (H&E) and, if feasible, with alcian blue or for mast cell markers (c-kit/tryptase).

Endoscopic images and videos are recorded at V1 and V4 to assess changes in glomerulations, Hunner's lesions, and overall mucosal appearance.

Statistical analysis plan

Primary analysis (safety): Descriptive statistics - frequency and percentage of participants with adverse events (AEs) grade ≥2 according to CTCAE v5.0, and frequency of SAEs.

Secondary analysis (efficacy): Continuous variables (VAS, ICSI, PUF, functional bladder capacity, voiding frequency) are compared between baseline and follow-up time points (week 4, month 3) using paired t-test (if normally distributed) or Wilcoxon signed-rank test (if non-normal). Categorical variables (PGI-I response) are reported as proportions with exact 95% confidence intervals.

Missing data: No imputation for missing values; analysis is per protocol.

Software: SPSS (version 26 or later) or R.

Significance level: α = 0.05 (two-sided), no adjustment for multiple comparisons (pilot, exploratory).

Data monitoring and quality control The study is conducted at a single tertiary care center (Sverdlovsk Regional Clinical Hospital No. 1, Yekaterinburg). An independent data safety monitoring board (DSMB) is not planned because this is a low-risk pilot study. However, all adverse events are reviewed weekly by the principal investigator. Serious adverse events are reported to the local ethics committee within 24 hours. Source data verification will be performed by the sponsor (the institution) according to its standard operating procedures.

Duration of participation Each participant is expected to be in the study for approximately 6 months (screening through month-6 follow-up). The optional repeat injection extends active treatment to 2 injections (day 0 and week 4).

Funding and sponsorship The study is investigator-initiated and funded by the Sverdlovsk Regional Clinical Hospital No. 1. No commercial funding is involved.

Study Type

Interventional

Enrollment (Estimated)

15

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Men and women aged ≥ 18 years.
  • Confirmed diagnosis of Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) based on cystoscopic findings (glomerulations after hydrodistension or Hunner's lesions).
  • Refractory to at least 2 lines of standard therapy (e.g., dietary modifications, oral medications, intravesical hyaluronic acid instillations, hydrodistension) for ≥ 6 months.
  • Pain score ≥ 4 on a 0-10 Visual Analog Scale (VAS) at screening.
  • Ability and willingness to provide written informed consent and to complete a 3-day voiding diary.

Exclusion Criteria:

  • Active urinary tract infection (bacteriuria > 10⁴ CFU/mL).
  • History of genital herpes.
  • Severe renal failure (eGFR < 30 mL/min/1.73 m²).
  • Known allergy to hyaluronic acid or any component of the study product.
  • Pregnancy or breastfeeding.
  • Psychiatric disorders or substance abuse that would interfere with study participation.
  • Participation in another clinical study within 30 days prior to enrollment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Hyaluronic Acid Injection Group
Participants receive a single session of 20 submucosal injections of non-cross-linked hyaluronic acid into the bladder wall, with optional repeat at week 4.
Drug: Hyaluronic Acid (HA)
Non-cross-linked hyaluronic acid solution 10 mg/mL for submucosal injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Treatment-Related Adverse Events
Time Frame: From day of procedure up to 30 days
Adverse events (AEs) are assessed and graded using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. The analysis includes all participants who received at least one injection. The total number and proportion of participants experiencing any AE, as well as AEs of Grade 2 or higher, will be reported. This includes pre-specified expected events such as transient hematuria, urinary tract infection, and injection site pain. Higher scores on the CTCAE scale represent a more severe adverse event.
From day of procedure up to 30 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Interstitial Cystitis Symptom Index (ICSI) and Problem Index (ICPI) Scores
Time Frame: Baseline, Week 4, Month 3
Validated questionnaires (O'Leary-Sant) measuring symptom severity and bother. ICSI ranges 0-19, ICPI ranges 0-16. Higher scores indicate worse symptoms. A reduction of ≥30% from baseline is considered a response.
Baseline, Week 4, Month 3
Change in Pelvic Pain and Urgency/Frequency (PUF) Score
Time Frame: Baseline, Week 4, Month 3
Validated questionnaire assessing pelvic pain, urgency, and frequency. Total score ranges 0-35 (or 0-39 depending on version). Higher scores indicate greater symptom burden. A reduction of ≥30% from baseline is considered a response.
Baseline, Week 4, Month 3
Change in Pain Intensity Measured by Visual Analog Scale (VAS)
Time Frame: Baseline (screening), Week 4, Month 3
Pain intensity is assessed using a 0-10 Visual Analog Scale (VAS), where 0 = no pain and 10 = worst possible pain. A reduction of ≥2 points from baseline is considered a clinical response.
Baseline (screening), Week 4, Month 3
Change in Functional Bladder Capacity
Time Frame: Baseline, Week 4, Month 3
Assessed by 3-day voiding diary (average voided volume per micturition). Measured in milliliters (mL). An increase of ≥30 mL from baseline is considered a response.
Baseline, Week 4, Month 3
Patient Global Impression of Improvement (PGI-I)
Time Frame: Week 4, Month 3
A single-item scale where participants rate their overall change in bladder condition since treatment on a 7-point scale: 1 = very much better, 2 = much better, 3 = a little better, 4 = no change, 5 = a little worse, 6 = much worse, 7 = very much worse. Response is defined as a score of 1-3 (improvement).
Week 4, Month 3
Change in Quality of Life Measured by Short Form-36 (SF-36)
Time Frame: Baseline, Week 4, Month 3
Validated 36-item questionnaire assessing physical and mental health components. Scores are transformed to a 0-100 scale, with higher scores indicating better quality of life.
Baseline, Week 4, Month 3

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sverdlovsk Regional Clinical Hospital No.1

Investigators

  • Study Chair: Igor V Bazhenov, Professor, MD, Sverdlovsk Regional Clinical Hospital No.1

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 1, 2026

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

January 1, 2027

Study Registration Dates

First Submitted

June 14, 2026

First Submitted That Met QC Criteria

June 14, 2026

First Posted (Actual)

June 18, 2026

Study Record Updates

Last Update Posted (Actual)

June 18, 2026

Last Update Submitted That Met QC Criteria

June 14, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • U7-2026

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

This is a pilot phase I study with a small sample size. The informed consent form does not include provisions for sharing individual participant data with external researchers, and there is no established infrastructure at our institution for de-identifying and transferring such data. Therefore, there is no plan to make IPD available.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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