Bladder Instillations vs. Pelvic Floor Therapy for Interstitial Cystitis

Overseen By Lydia Kosovich, RN

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: William Beaumont Hospitals

Disqualifiers: Bladder cancer, Pregnancy, Neurologic disorder, 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: 17

Duration: 8 weeks

128 Participants Needed

Trial Summary

What is the purpose of this trial?

Women with interstitial cystitis/bladder pain syndrome (IC/BPS) have debilitating urinary frequency and urgency, and chronic pelvic or bladder pain perceived to be related to the bladder. Although many clinicians think that IC/BPS symptoms result from a bladder problem, tight pelvic floor muscles can cause similar symptoms and might be responsible for ICBPS symptoms instead of the bladder. Inadequate assessment of the problem leads to delays in treatment and often years of suffering. This clinical trial will test a bladder directed therapy (bladder instillations) compared to a course of pelvic floor physical therapy (PFPT) to assess the role of the pelvic floor as a major contributor to pelvic pain and voiding dysfunction in adult women with non-ulcerative IC/BPS. Early assessment of the pelvic floor muscles in patients with IC/BPS symptoms may prevent common delays in proper diagnosis and allow for early, more effective treatment.

Will I have to stop taking my current medications?

The trial requires that you do not start any new medications that affect bladder or muscle function, and ideally, you should stay on a stable dose of your current medications throughout the trial.

What data supports the effectiveness of bladder instillations as a treatment for interstitial cystitis?

Research shows that bladder instillation therapy, which involves putting medication directly into the bladder, is a common treatment for interstitial cystitis, especially when other treatments haven't worked. Studies have explored the safety and potential benefits of using liposomes (tiny fat particles) in bladder instillations, suggesting it could be a promising option. ^{1 2 3 4 5}

Is bladder instillation therapy or pelvic floor muscle training safe for humans?

Bladder instillation therapy, which involves putting medication directly into the bladder, is commonly used for interstitial cystitis/bladder pain syndrome and is generally considered safe. Pelvic floor muscle training, which includes exercises to strengthen pelvic muscles, is also safe and effective for conditions like urinary incontinence and pelvic organ prolapse. ^{2 3 6 7 8}

How is the treatment of bladder instillations and pelvic floor therapy unique for interstitial cystitis?

Bladder instillations involve directly introducing medication into the bladder, which can provide targeted relief for interstitial cystitis when other treatments fail. Pelvic floor therapy focuses on strengthening and relaxing the muscles around the bladder, offering a non-drug approach to managing symptoms. ^{1 2 3 9 10}

Research Team

Kenneth M Peters, MD

Principal Investigator

Beaumont Hospital-Royal Oak

Eligibility Criteria

This trial is for women aged 18-85 with interstitial cystitis/bladder pain syndrome (IC/BPS) symptoms for at least 6 months. They must not be pregnant, breastfeeding, or starting new medications affecting bladder/muscle function and should maintain a stable dose of current meds.

Inclusion Criteria

I am female.

I agree not to start new meds that could affect my bladder or muscles and to keep my other meds stable.

I am using birth control, am surgically sterile, or have not had a period for 12 months.

Exclusion Criteria

I haven't had bladder treatments for IC/BPS symptoms in the last 3 months.

You are unable to tolerate having one or two fingers inserted into your vagina for examination.

I've had physical therapy with internal manual techniques for my symptoms in the last 3 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either bladder instillations or pelvic floor physical therapy twice weekly for 8 weeks

8 weeks

16 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

1 visit (in-person)

Treatment Details

Interventions

• Bladder Instillations
• Pelvic Floor Physical Therapy

Trial Overview The study compares bladder instillations (bladder directed therapy) with pelvic floor physical therapy to see which is more effective in treating pelvic pain and voiding dysfunction caused by IC/BPS in adult women without ulcerative conditions.

Participant Groups

Group I: Pelvic Floor Physical Therapy Active Control 1 Intervention

One hour of pelvic floor physical therapy twice weekly for 8 weeks

Group II: Bladder Instillations Active Control 1 Intervention

Bladder instillation of lidocaine, kenalog, heparin sulphate, and bicarbonate twice weekly for 8 weeks

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

Approved in United States as Bladder Instillations for:

• Interstitial cystitis/bladder pain syndrome (IC/BPS)

Approved in Canada as Bladder Instillations for:

• Interstitial cystitis/bladder pain syndrome (IC/BPS)

Approved in European Union as Bladder Instillations for:

• Interstitial cystitis/bladder pain syndrome (IC/BPS)

Who Is Running the Clinical Trial?

William Beaumont Hospitals

Lead Sponsor

Trials

153

Recruited

113,000+

Baylor College of Medicine

Collaborator

Trials

1,044

Recruited

6,031,000+

Findings from Research

Intravesical instillation of botulinum toxin A (BoNTA) is the most effective treatment for interstitial cystitis/painful bladder syndrome (IC/PBS), showing an 81.7% probability of being the best option based on global response assessments from a network meta-analysis of 16 trials involving 905 patients.

Both BoNTA and bacillus Calmette-Guerin (BCG) treatments significantly improve bladder capacity and urinary urgency symptoms compared to placebo, while pentosan polysulfate (PPS) effectively reduces urinary frequency and urgency in IC/PBS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravesical treatment for interstitial cystitis/painful bladder syndrome: a network meta-analysis. Zhang, W., Deng, X., Liu, C., et al.[2018]

In a study involving 14 subjects with interstitial cystitis/bladder pain syndrome, intravesical instillation of sphingomyelin liposomes was found to be safe, with no treatment-related adverse events reported during the 4-week treatment period.

The treatment led to significant improvements in pain and urinary urgency, as measured by visual analog scales and symptom indices, indicating potential efficacy for managing symptoms of IC/BPS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal bladder instillations for IC/BPS: an open-label clinical evaluation. Peters, KM., Hasenau, D., Killinger, KA., et al.[2021]

Bladder instillation therapy is an effective treatment for interstitial cystitis/bladder pain syndrome (IC/BPS) in patients who have not responded to other treatments, with three recommended medications: dimethyl sulfoxide, heparin, and lidocaine.

The review also highlights the need for further research into bladder instillation strategies and potential new therapies, as current recommendations are based on existing evidence but do not encompass all possible treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current recommendations for bladder instillation therapy in the treatment of interstitial cystitis/bladder pain syndrome. Colaco, MA., Evans, RJ.[2021]

The O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI) and Interstitial Cystitis Problem Index (ICPI) effectively measure treatment outcomes for interstitial cystitis (IC) after hydrodistention (HD) and bladder training (BT), showing significant improvement in scores from pre-treatment to three months post-treatment.

In a study of 108 patients, the average scores for both ICSI and ICPI dropped dramatically after treatment, indicating that these questionnaires are not only useful for screening but also for assessing the efficacy of IC treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of treatment outcomes of interstitial cystitis with hydrodistention and bladder training by O'Leary-Sant Interstitial Cystitis Symptom and Problem Indices. Huang, MC., Hsieh, CH., Chang, WC., et al.[2019]

Intravesical therapy, particularly using liposomes and polymers, has shown promise in enhancing the delivery and efficacy of treatments for urinary tract disorders like interstitial cystitis and overactive bladder, with improvements noted in rodent models.

The review highlights the potential of repurposing existing drugs, such as tacrolimus, for intravesical use, which may lead to better clinical outcomes and safety profiles for patients with lower urinary tract conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in intravesical therapy for urinary tract disorders. Tyagi, P., Kashyap, M., Hensley, H., et al.[2018]

Biofeedback pelvic floor muscle training (PFMT) was found to be effective for treating dysfunctional voiding (DV) in women, with 80.6% of participants showing significant improvements in symptoms and quality of life after a 3-month program involving 31 patients.

Improvements were also noted in uroflowmetry parameters, such as maximum flow rate and voiding efficiency, but a history of recurrent urinary tract infections within the past year negatively impacted treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic efficacy of biofeedback pelvic floor muscle exercise in women with dysfunctional voiding. Chiang, CH., Jiang, YH., Kuo, HC.[2021]

Unsupervised behavioral and pelvic floor muscle training (B-PFMT) programs significantly improve urinary incontinence (UI) outcomes and pelvic floor muscle strength in middle-aged women, as shown in a review of 13 studies, including 10 randomized controlled trials.

Two months after the intervention, participants experienced a reduction in incontinent episodes and improved quality of life scores, indicating the effectiveness of B-PFMT for managing UI symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unsupervised behavioral and pelvic floor muscle training programs for storage lower urinary tract symptoms in women: a systematic review. Wu, C., Newman, DK., Palmer, MH.[2021]

Pelvic floor muscle training (PFMT) is an effective and comprehensive treatment for pelvic floor disorders like urinary incontinence and pelvic organ prolapse, involving exercises tailored by trained clinicians.

Despite its proven efficacy and cost-effectiveness, PFMT is not widely adopted as a first-line treatment in the USA, highlighting a gap in clinical practice that could improve women's health outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pelvic Floor Muscle Training: Underutilization in the USA. Lamin, E., Parrillo, LM., Newman, DK., et al.[2018]

In a study involving 5 female patients with interstitial cystitis, prolonged intravesical instillation of resiniferatoxin (RTX) significantly reduced urinary frequency from 11.3 to 7.4 and nocturia from 3.6 to 1.2 after 30 days, indicating its efficacy in managing symptoms.

Patients also experienced a significant decrease in pain scores from 6.7 to 2.4, with effects lasting up to three months, and no side effects were reported during or after the treatment, highlighting the safety of this delivery method.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravesical infusion of resiniferatoxin by a temporary in situ drug delivery system to treat interstitial cystitis: a pilot study. Lazzeri, M., Spinelli, M., Beneforti, P., et al.[2019]

A new non-invasive method for instilling bladder cocktails through a specially designed adapter allows for effective treatment of interstitial cystitis/bladder pain syndrome without the need for catheterization, achieving a 98% success rate in female patients and 100% in male patients.

This method significantly reduces pain and complications associated with traditional catheterization, as no infections or adverse effects were reported, making it a preferred option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Minimally invasive device for intravesical instillation by urological syringe adapter (MID-ii U.S.A.) for catheter-free instillation therapy of the bladder in interstitial cystitis/bladder pain syndrome. Lovasz, S.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

Intravesical treatment for interstitial cystitis/painful bladder syndrome: a network meta-analysis. [2018]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Liposomal bladder instillations for IC/BPS: an open-label clinical evaluation. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Current recommendations for bladder instillation therapy in the treatment of interstitial cystitis/bladder pain syndrome. [2021]

4. China (Republic : 1949- ) pubmed.ncbi.nlm.nih.gov

Assessment of treatment outcomes of interstitial cystitis with hydrodistention and bladder training by O'Leary-Sant Interstitial Cystitis Symptom and Problem Indices. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Advances in intravesical therapy for urinary tract disorders. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Therapeutic efficacy of biofeedback pelvic floor muscle exercise in women with dysfunctional voiding. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Unsupervised behavioral and pelvic floor muscle training programs for storage lower urinary tract symptoms in women: a systematic review. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Pelvic Floor Muscle Training: Underutilization in the USA. [2018]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Intravesical infusion of resiniferatoxin by a temporary in situ drug delivery system to treat interstitial cystitis: a pilot study. [2019]

10. Australia pubmed.ncbi.nlm.nih.gov

Minimally invasive device for intravesical instillation by urological syringe adapter (MID-ii U.S.A.) for catheter-free instillation therapy of the bladder in interstitial cystitis/bladder pain syndrome. [2020]