ICE-MRI Bladder Permeability Assay for Interstitial Cystitis

Overseen By Vickie Polanco-Garcia

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Christopher J Chermansky, MD

Must not be taking: Analgesics, Anti-inflammatories

Disqualifiers: Urinary incontinence, Urologic malignancy, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to better understand Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) by examining bladder permeability, or how "leaky" the bladder is. Participants will undergo an MRI scan using special contrast agents, Ferumoxytol (Feraheme) and Gadobutrol (Gadavist or Gadobutrol Injection), to determine if these agents enter the bladder wall, which could indicate IC. The trial focuses on individuals diagnosed with IC/BPS who experience pain related to bladder storage, urgency, or frequent nighttime urination. Participants should not have conditions like urinary tract infections or a history of urologic cancer. As an Early Phase 1 trial, this research seeks to understand how these agents work in people, offering participants a chance to contribute to pioneering research.

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 prior data suggests that this MRI technique is safe for assessing bladder permeability?

Research has shown that Gadobutrol is generally safe for MRI scans. Most allergic reactions occur within 30 minutes, though some may appear days later. Serious issues, such as seizures, are rare and typically involve direct brain exposure, which this trial does not include.

The safety of Ferumoxytol remains under study. Previous research has indicated its safety for MRI scans, and it is being compared to other common MRI agents for confirmation.

This trial uses both Gadobutrol and Ferumoxytol. Both have demonstrated safety for medical imaging. However, as with any medical procedure, a small risk of side effects exists. Participants will receive close monitoring to ensure their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for interstitial cystitis focus on alleviating symptoms through oral medications, bladder instillations, or nerve stimulation. But the ICE-MRI Bladder Permeability Assay is different because it seeks to improve diagnosis and understanding of the condition rather than directly treating symptoms. Researchers are excited about this method because it uses a novel combination of contrast agents, ferumoxytol and gadobutrol, delivered directly into the bladder, allowing for a detailed MRI assessment of bladder permeability. This could lead to more precise targeting of treatments and better understanding of disease mechanisms, potentially transforming how interstitial cystitis is managed in the future.

What evidence suggests that this MRI technique is effective for identifying Interstitial Cystitis?

In this trial, participants will undergo an ICE-MRI procedure using a combination of Gadobutrol and Ferumoxytol to better understand interstitial cystitis (IC). Research has shown that using Gadobutrol and Ferumoxytol together can highlight changes in how the bladder wall allows substances to pass through. Studies have found that IC patients with Hunner's lesions—painful sores in the bladder—tend to have more Gadobutrol in their bladder wall. This suggests that these substances in imaging can identify specific bladder changes related to IC. Gadobutrol and Ferumoxytol enhance MRI scans to create clearer pictures of the bladder, aiding in the diagnosis and understanding of IC severity. Early evidence suggests this method might effectively distinguish different types of bladder pain syndrome, helping to provide targeted treatment. ^{6 7 8 9 10}

Who Is on the Research Team?

Christopher Chermansky, MD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

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

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Ferumoxytol
• Gadobutrol

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

This study demonstrates that contrast-enhanced magnetic resonance imaging (MRI) can effectively quantify bladder permeability in patients with interstitial cystitis, showing significant differences in signal intensity between affected and control bladders.

The findings suggest that increased bladder permeability may be linked to the symptoms of interstitial cystitis, providing a potential objective measure for diagnosing and monitoring treatment in bladder pain patients.

NCBI (Pubmed)

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. Towner, RA., Wisniewski, AB., Wu, DH., et al.[2018]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6234747/

Recent advances in imaging and understanding interstitial ... This review will cover recent developments in imaging methods, such as magnetic resonance imaging, that advance the understanding of IC/BPS and guide drug ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12199307/

Unraveling the complexity of bladder-centric chronic pain by ... This article aims to delve into the pathophysiology of bladder-centric chronic pain within the context of the challenging diagnosis of IC/BPS.

3. nature.com nature.com/articles/s41598-021-98504-9

Functional and histologic imaging of urinary bladder wall ... T1 mapping of urinary bladder wall at 9.4 T was performed pre- and post- instillation of 4 mM Gadobutrol in a mixture with 5 mM Ferumoxytol.

4. researchgate.net researchgate.net/publication/328846080_Recent_advances_in_imaging_and_understanding_interstitial_cystitis

Recent advances in imaging and understanding interstitial ... Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating condition associated with intense pelvic pain and bladder storage ...

5. mdpi.com mdpi.com/1718-7729/30/5/350

Intravesical Contrast-Enhanced MRI: A Potential Tool for ... Transurethral instillation of 0.05 mL Gadobutrol (4 mM) and Ferumoxytol (5 mM) for a 30 min period accomplishes voxel-wise T1 mapping at a ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2011/201277s000lbl.pdf

Gadavist (gadobutrol) injection - accessdata.fda.gov Most hypersensitivity reactions to Gadavist have occurred within half an hour after administration. Delayed reactions can occur up to several days after ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5582910/

Novel contrast mixture improves bladder wall ... CCE-MRI following instillation of contrast mixture identifies bladder wall changes likely associated with bladder injury with improved image contrast. Keywords: ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10156572/

Ferumoxytol vs Gadolinium Agents for Contrast Enhanced MRI Multicenter pooled analysis of safety data relating to the diagnostic use of ferumoxytol is underway. In March of 2015, the FDA issued a ...

9. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2019/201277s017lbl.pdf

GADAVIST (gadobutrol) injection, for intravenous use The safety and effectiveness of Gadavist have been established in pediatric patients, including term neonates, for use with. MRI to detect and visualize areas ...

10. radiologysolutions.bayer.com radiologysolutions.bayer.com/products/contrast-agents/gadavist-injection-pi

Gadavist (gadobutrol) injection pi Intrathecal administration of gadolinium-based contrast agents (GBCAs) can cause serious adverse reactions including death, coma, encephalopathy, and seizures.