Trospium for Urinary Incontinence

Overseen By Becky Clarkson, PhD

Age: 18+

Sex: Female

Trial Phase: Phase 4

Sponsor: Becky Clarkson

Must not be taking: Anticholinergics

Disqualifiers: Impaired mobility, Neurological condition, Prolapse, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

220 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a randomized double-blind crossover trial of trospium and placebo in women with urgency urinary incontinence, with evaluation (history, physical, incontinence evaluation and brain MRI) at baseline, and after each course of therapy. The investigators will evaluate functional brain changes in relation to bladder improvement in order to improve our knowledge of the brain's role in the continence mechanism.

Will I have to stop taking my current medications?

If you are currently taking anticholinergic medications, you will need to stop them for 4 weeks before joining the trial. The protocol does not specify other medication restrictions, but any drug interactions or expected medication changes during the study may affect eligibility.

What evidence supports the effectiveness of the drug trospium chloride for urinary incontinence?

Research shows that trospium chloride is effective in reducing symptoms of overactive bladder, such as frequent urination and urgency, and it has been used successfully in Europe for over 10 years. It also has a better safety profile compared to another similar drug, oxybutynin, making it a favorable option for treating urinary incontinence. ^{1 2 3 4 5}

Is trospium safe for humans?

Trospium chloride, used for overactive bladder, has been shown to have a favorable safety profile with a low incidence of side effects, especially on the central nervous system. It has been well tolerated in studies, even when used in combination with other medications, and has been prescribed in Europe for over 20 years. ^{1 2 4 6 7}

How does the drug trospium differ from other treatments for urinary incontinence?

Trospium is unique because it is an anticholinergic drug that specifically targets overactive bladder symptoms and has been shown to be effective in both normal and obese patients. It is known for its favorable safety profile and minimal side effects, making it suitable for long-term use, especially in preparation for surgical interventions. ^{1 2 4 8 9}

Research Team

Becky Clarkson, PhD

Principal Investigator

University of Pittsburgh

Eligibility Criteria

This trial is for women over 60 with urgency urinary incontinence (UUI) or urge-predominant mixed incontinence, occurring at least five times a week for more than three months despite treatment. Participants must not have certain medical conditions like spinal cord injury, severe pelvic issues, or be on conflicting medications.

Inclusion Criteria

I have had frequent urges to urinate or accidents for more than 3 months, despite treatment.

I am 60 years old or older.

Exclusion Criteria

I have bowel control issues and symptoms of colitis or IBS.

I have had radiation in my pelvic area or have advanced cancer in my uterus or bladder.

I have previously been treated for urinary incontinence with Botox or nerve stimulation.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Evaluation

Evaluation including history, physical, incontinence evaluation, and brain MRI

1 week

1 visit (in-person)

Treatment Phase 1

Participants receive either placebo or trospium for 12 weeks

12 weeks

Regular visits for monitoring

Treatment Phase 2

Crossover to receive the alternate treatment (trospium or placebo) for 12 weeks

12 weeks

Regular visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Placebo oral tablet
• Trospium

Trial Overview The study tests the effectiveness of Trospium against a placebo in managing UUI symptoms and examines how the brain responds to these treatments using MRI scans. It's a randomized double-blind crossover trial, meaning participants will receive both the drug and placebo at different times without knowing which one they're taking.

Participant Groups

Group I: Trospium/Placebo Experimental Treatment 2 Interventions

Trospium first for 12 weeks followed by Placebo for 12 weeks

Group II: Placebo/Trospium Experimental Treatment 2 Interventions

Placebo first for 12 weeks followed by Trospium for 12 weeks.

Trospium is already approved in United States, European Union for the following indications:

Approved in United States as Sanctura for:

• Overactive bladder syndrome (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency

Approved in European Union as Regurin for:

• Overactive bladder syndrome (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency

Who Is Running the Clinical Trial?

Becky Clarkson

Lead Sponsor

Trials

1

Recruited

220+

Neil M. Resnick

Lead Sponsor

Trials

1

Recruited

220+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Findings from Research

Obesity is linked to a more severe state of overactive bladder (OAB), as shown in a study of 1,165 subjects, indicating that overweight and obese patients may experience worse symptoms.

Trospium chloride XR, taken once daily, was found to be significantly more effective than a placebo in reducing OAB symptoms, such as toilet voids and urgency, in obese patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obesity is associated with a more severe overactive bladder disease state that is effectively treated with once-daily administration of trospium chloride extended release. Chancellor, MB., Oefelein, MG., Vasavada, S.[2013]

Trospium chloride (Sanctura) is effective in relieving symptoms of overactive bladder (OAB) and has a favorable safety profile, with adverse events similar to placebo except for minor issues like dry mouth and constipation.

It is fast-acting and does not interact with other medications metabolized by cytochrome P450, making it a safe and convenient treatment option for the approximately 17% of US adults affected by OAB.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trospium chloride: an anticholinergic quaternary ammonium compound for the treatment of overactive bladder. Zinner, NR.[2019]

Trospium chloride (Spazmex) is effective in treating neurogenic overactive bladder in patients with Parkinson's disease, as shown by a significant reduction in urination frequency and improvement in quality of life over a 52-week treatment period involving 60 patients.

Long-term use of trospium chloride does not negatively impact cognitive functions, making it a safe first-line treatment option for urologic symptoms in Parkinson's disease patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Long-term safety and efficacy of trospium chloride for the treatment of neurogenic overactive bladder due to Parkinson's disease is there an effect on cognitive status?] Korshunova, ES., Andreev, MN., Korshunov, MN., et al.[2023]

In a study involving 20 women with imperative voiding syndrome, the combination of Spasmex (trospium chloride) and alpha 1-adrenoblockers significantly improved clinical symptoms, with a twofold improvement observed after 4 weeks of treatment.

The treatment also increased the mean effective capacity of the urinary bladder by 25%, and it was well tolerated with no reported side effects, indicating its safety and efficacy for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Combined treatment of voiding disorders in women with m-cholinolytic and alpha 1-adrenoblocker]. Danilov, VV., Vol'nykh, IIu., Abdullaeva, CK., et al.[2016]

Trospium chloride, administered at 20 mg twice daily for 52 weeks, demonstrated significant efficacy in reducing micturition frequency, incontinence, and urgency events in patients with urge syndrome, with a notable increase in bladder capacity by 115 ml after treatment.

Trospium chloride had a better tolerability profile compared to oxybutynin, with lower rates of adverse events (64.8% vs. 76.7%) and a significantly reduced risk of dryness of the mouth, making it a safer option for long-term therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Controlled, double-blind, multicentre clinical trial to investigate long-term tolerability and efficacy of trospium chloride in patients with detrusor instability. Halaska, M., Ralph, G., Wiedemann, A., et al.[2022]

Trospium chloride is an effective treatment for overactive bladder symptoms, such as urge incontinence and urinary frequency, with a unique pharmacologic profile that sets it apart from other antimuscarinic agents.

The drug has a low incidence of central nervous system side effects, making it a safer option for patients, and it demonstrates quick onset of action for relieving urgency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trospium chloride: Distinct among other anticholinergic agents available for the treatment of overactive bladder. Staskin, DR.[2013]

In a large observational study involving 669 patients with idiopathic overactive bladder, an individualized dosing approach for trospium chloride was found to be effective and safe over a 12-week period.

Patients adjusted their doses based on treatment response and side effects, with the majority receiving doses between 45 mg and 60 mg per day, highlighting the importance of personalized treatment in managing symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[High doses of trospium chloride in patients with idiopathic overactive bladder. Data of large-scale, multicenter observational program Resource]. Krivoborodov, GG., Tur, EI., Efremov, NS., et al.[2017]

Non-invasive uroflowmetric monitoring shows that hyperactive bladder and stress urinary incontinence in women share similar functional disorders, indicating a need for comprehensive assessment before surgery.

Long-term treatment with M-cholinolytics, specifically spasmex (trospium chloride), is recommended for patients, as it has minimal side effects and significantly improves conditions for planning surgical interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[M-cholinolytic spasmex and its role in preoperative preparation of patients with urine incontinence]. Danilov, VV., Danilova, TI.[2013]

In a study using isolated human detrusor smooth muscle strips, trospium chloride and tolterodine were found to be more effective than oxybutynin and flavoxate in relaxing muscle tension caused by muscarinic stimulation, indicating their potential superiority in treating urinary incontinence.

All tested drugs, including flavoxate, oxybutynin, tolterodine, and trospium chloride, demonstrated concentration-dependent effects in reducing muscle contractions, with trospium chloride and tolterodine showing the most pronounced effects, supporting their use in managing overactive bladder symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Responses of isolated normal human detrusor muscle to various spasmolytic drugs commonly used in the treatment of the overactive bladder. Uckert, S., Stief, CG., Odenthal, KP., et al.[2015]

References

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

Obesity is associated with a more severe overactive bladder disease state that is effectively treated with once-daily administration of trospium chloride extended release. [2013]

2. England pubmed.ncbi.nlm.nih.gov

Trospium chloride: an anticholinergic quaternary ammonium compound for the treatment of overactive bladder. [2019]

3. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Long-term safety and efficacy of trospium chloride for the treatment of neurogenic overactive bladder due to Parkinson's disease is there an effect on cognitive status?] [2023]

4. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Combined treatment of voiding disorders in women with m-cholinolytic and alpha 1-adrenoblocker]. [2016]

5. Germany pubmed.ncbi.nlm.nih.gov

Controlled, double-blind, multicentre clinical trial to investigate long-term tolerability and efficacy of trospium chloride in patients with detrusor instability. [2022]

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

Trospium chloride: Distinct among other anticholinergic agents available for the treatment of overactive bladder. [2013]

7. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[High doses of trospium chloride in patients with idiopathic overactive bladder. Data of large-scale, multicenter observational program Resource]. [2017]

8. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[M-cholinolytic spasmex and its role in preoperative preparation of patients with urine incontinence]. [2013]

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

Responses of isolated normal human detrusor muscle to various spasmolytic drugs commonly used in the treatment of the overactive bladder. [2015]