ICE-MRI Bladder Permeability Assay for Interstitial Cystitis

Recruiting in Palo Alto (17 mi)

Overseen by Christopher Chermansky, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: Christopher J Chermansky, MD

Must not be taking: Analgesics, Anti-inflammatories

Disqualifiers: Urinary incontinence, Urologic malignancy, Diabetes, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

Each participant will be asked to participate in this research study which distinguishes different types of Interstitial Cystitis/Bladder Pain Syndrome. Research studies include only people who wish to participate. The study team members will explain the study to each participant, and all questions about the study will be answered. Each participant will be given adequate time when deciding to participate in this study. Should the participant consent to participate, then the participant will agree to undergo have a single Magnetic Resonance Imaging (MRI) test that involves the use of radio waves and a powerful magnet which are linked to a computer that looks at the bladder. The MRI test is being performed to see if the bladder is leaky, which would suggest Interstitial Cystitis (IC). The MRI test involves placing Gadobutrol and Ferumoxytol into the bladder using a sterile catheter, a small hollow tube through which fluids pass. Preliminary data suggests that IC patients with Hunners lesions have increased Gadobutrol in the bladder wall lining.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any pain relievers or anti-inflammatory drugs, including steroids, for one week before the MRI test.

What data supports the effectiveness of the drug Ferumoxytol, Feraheme, Gadobutrol, Gadavist, Gadobutrol Injection for treating interstitial cystitis?

The research suggests that contrast-enhanced MRI using gadobutrol and ferumoxytol can help measure bladder permeability and inflammation, which are important in understanding interstitial cystitis. This imaging approach may aid in assessing the condition and evaluating potential therapies, although direct evidence of the drug's effectiveness for treatment is not provided. ^{1 2 3 4 5}

Is the ICE-MRI Bladder Permeability Assay for Interstitial Cystitis safe for humans?

Gadobutrol, used in MRI scans, is generally well tolerated and has a lower risk of causing nephrogenic systemic fibrosis (a rare but serious condition) compared to other similar agents. Ferumoxytol is also considered safe and is used as an alternative in patients with kidney issues, as it does not carry the same risks as gadolinium-based agents. ^{6 7 8 9 10}

How does the ICE-MRI Bladder Permeability Assay treatment differ from other treatments for interstitial cystitis?

The ICE-MRI Bladder Permeability Assay is unique because it uses a novel contrast mixture in MRI to assess bladder permeability and inflammation, which is not a standard diagnostic or treatment approach for interstitial cystitis. This method provides a non-invasive way to visualize and measure changes in the bladder wall, potentially offering insights into the condition that other treatments do not. ^{2 3 4 5 11}

Research Team

Christopher Chermansky, MD

Principal Investigator

University of Pittsburgh

Eligibility Criteria

This trial is for adults aged 18-80 with Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS), experiencing pain related to bladder filling and relief upon emptying. It includes those with Hunner lesions or without, and control subjects without cystoscopic abnormalities. Excluded are individuals with urinary issues like incontinence, UTI history, spinal cord injury, urologic cancer history, certain surgeries or treatments, high creatinine levels, diabetes, untreated hypertension, proteinuria; also excluded are those who can't have an MRI due to metal implants or claustrophobia.

Inclusion Criteria

I wake up to urinate more than once a night.

I am between 18 and 80 years old and have been diagnosed with IC/BPS, with or without Hunner lesions.

I experience pain in my lower abdomen or pelvic area that gets better after I urinate.

Exclusion Criteria

You are afraid of small or enclosed spaces.

I have had multiple urinary tract infections.

I cannot stop taking pain or anti-inflammatory medication for a week before an MRI.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Cystoscopy

Cystoscopy performed if not done within the last 6 months to determine type of Interstitial Cystitis

2-4 weeks after visit 1

1 visit (in-person)

MRI Imaging

Participants undergo a single MRI test to assess bladder permeability using contrast agents

90 minutes

1 visit (in-person)

Follow-up

Participants are monitored for any immediate adverse effects post-MRI

1 week

Treatment Details

Interventions

• Ferumoxytol (Iron Supplement)
• Gadobutrol (Contrast Agent)

Trial Overview The study tests the use of ICE-MRI Bladder Permeability Assay using Gadobutrol and Ferumoxytol to identify leakiness in the bladder wall lining which may indicate IC/BPS. Participants will undergo a single MRI scan where these substances are introduced into the bladder via catheter to assess differences between types of IC/BPS.

Participant Groups

Group I: ICE-MRI Experimental Treatment 2 Interventions

Participants will undergo a single Magnetic Resonance Imaging study: a single breath-hold pre-contrast image followed by sterile placement of a temporary urethral catheter for instillation of a 50 milliliter (mL) solution containing Gadobutrol (302mg) plus ferumoxytol (5 mM) and a second, single breath hold post-contrast image.

Who Is Running the Clinical Trial?

Christopher J Chermansky, MD

Lead Sponsor

Trials

3

Recruited

50+

Lipella Pharmaceuticals, Inc.

Industry Sponsor

Trials

4

Recruited

70+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Dr. Jeanne Marrazzo

National Institutes of Health (NIH)

Chief Medical Officer

MD from University of California, Los Angeles

Dr. Jay Bhattacharya

National Institutes of Health (NIH)

Chief Executive Officer

MD, PhD from Stanford University

Findings from Research

The intravesical ethanol test was conducted on 3 patients with interstitial cystitis, but it failed to detect any levels of ethanol, indicating that it may not be an effective measure of bladder hyperpermeability.

Despite the lack of detectable ethanol, the test did not cause significant pain or irritative symptoms, suggesting that it is safe to perform, but further investigation with higher ethanol concentrations may be needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravesical ethanol test: an ineffective measure of bladder hyperpermeability. Gordon, Z., Parsons, CL., Monga, M.[2019]

Quantitative T1 relaxometry using a novel contrast mixture (NCM) effectively measures bladder wall permeability and chronic inflammation in irradiated mice, showing significant differences in T1 relaxation times before and after contrast instillation.

The study found that gadobutrol permeability was nearly twofold higher in the urothelium of irradiated mice compared to controls, and MRI results correlated with histological findings of inflammation and bladder wall thickening, indicating the method's potential for assessing bladder conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Virtual measurements of paracellular permeability and chronic inflammation via color coded pixel-wise T1 mapping. Singh, N., Zabbarova, I., Ikeda, Y., et al.[2022]

A new contrast-enhanced magnetic resonance imaging (CE-MRI) technique has been developed to assess bladder wall hyperpermeability (BWH) in patients with interstitial cystitis/bladder pain syndrome (IC/BPS), which could help in diagnosing and evaluating the severity of the condition.

MRI methodologies, including molecular-targeted MRI (mt-MRI) and diffusion-weighted imaging (DWI), show promise in identifying biomarkers and structural changes associated with IC/BPS, potentially paving the way for future clinical trials and therapeutic assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MRI as a Tool to Assess Interstitial Cystitis Associated Bladder and Brain Pathologies. Towner, RA., Smith, N., Saunders, D., et al.[2021]

A study measuring bladder permeability in 10 interstitial cystitis patients compared to 9 healthy volunteers found no significant difference in permeability between the two groups, suggesting that increased bladder permeability is not a characteristic of interstitial cystitis.

The research involved direct measurement using a radionuclide infusion method, and while individual variability was noted, the overall results did not support the idea that interstitial cystitis patients have a more permeable bladder than symptom-free individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bladder permeability in interstitial cystitis is similar to that of normal volunteers: direct measurement by transvesical absorption of 99mtechnetium-diethylenetriaminepentaacetic acid. Chelsky, MJ., Rosen, SI., Knight, LC., et al.[2019]

Gadobutrol, a second-generation gadolinium-based contrast agent, is effective for enhancing MRI images across various medical fields, allowing for better visualization of pathological lesions and improved diagnostic capabilities.

It is generally well tolerated in a wide range of patients, including those with renal or hepatic impairments, and has a lower risk of causing nephrogenic systemic fibrosis compared to older linear GBCAs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gadobutrol: a review of its use for contrast-enhanced magnetic resonance imaging in adults and children. Scott, LJ.[2021]

In a study involving ten pediatric patients with chronic kidney disease, ferumoxytol was successfully used as a contrast agent for MR angiography, showing clear and diagnostic images without complications.

Ferumoxytol presents a promising alternative to gadolinium-based contrast agents, which can pose serious risks like nephrogenic systemic fibrosis in patients with kidney issues, highlighting its potential safety and efficacy in this vulnerable population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-resolution, whole-body vascular imaging with ferumoxytol as an alternative to gadolinium agents in a pediatric chronic kidney disease cohort. Nayak, AB., Luhar, A., Hanudel, M., et al.[2021]

Ferumoxytol (FE) can provide comparable image quality to gadolinium-based contrast agents (GBCAs) in first pass magnetic resonance angiography (MRA), despite GBCAs showing significantly higher contrast-to-noise ratios (CNR).

In a study involving 12 healthy volunteers, optimized doses of FE (4 mg/kg and 2 mg/kg) were evaluated, revealing that while FE had lower CNR, it maintained image quality and did not show a decrease in CNR five minutes post-injection, suggesting its potential as a safe alternative to GBCAs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crossover comparison of ferumoxytol and gadobenate dimeglumine for abdominal MR-angiography at 3.0 tesla: Effects of contrast bolus length and flip angle. Schubert, T., Motosugi, U., Kinner, S., et al.[2018]

In a study involving 53 prostate cancer patients, gadobutrol showed significantly higher relative peak enhancement compared to Gd-DTPA in dynamic contrast-enhanced MRI (DCE-MRI), indicating it may provide better imaging quality.

Despite the enhanced peak with gadobutrol, there were no significant differences in the types of enhancement curves or pharmacokinetic parameters between the two contrast media, suggesting similar overall performance in assessing prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dynamic contrast enhanced MRI of the prostate: comparison of gadobutrol and Gd-DTPA. Durmus, T., Vollnberg, B., Schwenke, C., et al.[2022]

In a study involving 229 adult patients with suspected brain tumors, gadobutrol and gadoteridol were found to provide similar effectiveness in enhancing MR imaging for lesion detection and characterization, despite gadobutrol being at a higher concentration.

There were no significant differences in adverse events between the two contrast agents, indicating that both are safe options for patients undergoing brain imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are there differences between macrocyclic gadolinium contrast agents for brain tumor imaging? Results of a multicenter intraindividual crossover comparison of gadobutrol with gadoteridol (the TRUTH study). Maravilla, KR., Smith, MP., Vymazal, J., et al.[2021]

Combined contrast-enhanced magnetic resonance imaging (CCE-MRI) using gadolinium and iron oxide-based agents effectively segmented the bladder wall from the bladder lumen in a study involving adult female Sprague-Dawley rats.

The technique showed a significant increase in image contrast, with the normalized signal in the bladder wall rising from 0.46 in the control group to 0.73 in the injury group, indicating its potential for detecting bladder injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel contrast mixture improves bladder wall contrast for visualizing bladder injury. Tyagi, P., Janicki, JJ., Hitchens, TK., et al.[2018]

References

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

Intravesical ethanol test: an ineffective measure of bladder hyperpermeability. [2019]

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

Virtual measurements of paracellular permeability and chronic inflammation via color coded pixel-wise T1 mapping. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

MRI as a Tool to Assess Interstitial Cystitis Associated Bladder and Brain Pathologies. [2021]

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

Bladder permeability in interstitial cystitis is similar to that of normal volunteers: direct measurement by transvesical absorption of 99mtechnetium-diethylenetriaminepentaacetic acid. [2019]

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

A Feasibility Study to Determine Whether Clinical Contrast Enhanced Magnetic Resonance Imaging can Detect Increased Bladder Permeability in Patients with Interstitial Cystitis. [2018]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Gadobutrol: a review of its use for contrast-enhanced magnetic resonance imaging in adults and children. [2021]

7. Germany pubmed.ncbi.nlm.nih.gov

High-resolution, whole-body vascular imaging with ferumoxytol as an alternative to gadolinium agents in a pediatric chronic kidney disease cohort. [2021]

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

Crossover comparison of ferumoxytol and gadobenate dimeglumine for abdominal MR-angiography at 3.0 tesla: Effects of contrast bolus length and flip angle. [2018]

9. Germany pubmed.ncbi.nlm.nih.gov

Dynamic contrast enhanced MRI of the prostate: comparison of gadobutrol and Gd-DTPA. [2022]

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

Are there differences between macrocyclic gadolinium contrast agents for brain tumor imaging? Results of a multicenter intraindividual crossover comparison of gadobutrol with gadoteridol (the TRUTH study). [2021]

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

Novel contrast mixture improves bladder wall contrast for visualizing bladder injury. [2018]