Tizanidine for Urinary Retention

Overseen By Jungeun Lee, MS

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: NorthShore University HealthSystem

Disqualifiers: Age <18, Colorectal surgery, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether the medication tizanidine can prevent urinary retention (difficulty urinating) after pelvic reconstructive surgery. Tizanidine, a muscle relaxant, might ease urination by relaxing muscles around the urethra. The trial aims to determine if taking tizanidine before surgery reduces the need for catheters, which can be uncomfortable and cause infections. Women planning to undergo sacrospinous ligament suspension surgery, without a history of urinary retention, might be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that Tizanidine is likely to be safe for humans?

Research shows that Tizanidine is generally well-tolerated by patients. One study with children experiencing urinary problems found that Tizanidine caused few side effects, suggesting it could be a safe option for similar conditions in adults. Tizanidine is also FDA-approved for treating muscle stiffness, indicating it has undergone safety testing in certain situations. However, like any medication, it might still cause some side effects. Common ones include sleepiness or dizziness, but these are usually not serious for most people. Overall, evidence supports that Tizanidine is a low-risk medication when used as directed. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for urinary retention?

Tizanidine is unique because it offers a fresh approach to managing urinary retention by using a muscle relaxant typically employed for spasticity. Unlike standard treatments like catheterization or medications such as alpha-blockers, which primarily target bladder outlet obstruction, Tizanidine acts on the central nervous system to reduce muscle tone and potentially improve bladder function. Researchers are excited because this mechanism might provide relief for patients who do not respond well to existing therapies, offering a new avenue for treating this condition.

What evidence suggests that Tizanidine might be an effective treatment for postoperative urinary retention?

Research suggests that tizanidine, a muscle relaxant, might help prevent urination problems after surgery. It relaxes muscles and blocks certain receptors, which can help the muscles around the urethra relax more easily, potentially improving urine flow. Although no studies have specifically tested tizanidine for this issue, it has been used successfully for other muscle problems, and its low risk makes it a promising option. This trial will investigate the use of tizanidine to reduce urinary retention after surgery, building on early findings in similar situations. ^{1 2 6 7 8}

Who Is on the Research Team?

Claudia Paya Ten, MD

Principal Investigator

Endeavor Health

Are You a Good Fit for This Trial?

This trial is for women who have had a specific pelvic reconstructive surgery called sacrospinous ligament suspension. It's not open to those who haven't had this procedure.

Inclusion Criteria

I have had a procedure to support my pelvic organs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-operative

Tizanidine 2mg is administered preoperatively prior to scheduled sacrospinous ligament suspension

1 day

1 visit (in-person)

Immediate Postoperative

Immediate postoperative evaluation for urinary retention and pain management

1 day

1 visit (in-person)

Follow-up

Participants are monitored for unplanned admissions, office visits, or encounters within 30 days after surgery

30 days

What Are the Treatments Tested in This Trial?

Interventions

• Tizanidine

Trial Overview The study tests if Tizanidine, a muscle relaxant and alpha-adrenergic blocker, can prevent urinary retention—a common issue where patients can't pee after the surgery mentioned above.

How Is the Trial Designed?

Group I: Tizanidine Experimental Treatment 1 Intervention

Tizanidine 2mg will be given preoperatively prior to scheduled sacrospinous ligament suspension

Tizanidine is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Zanaflex for:

• Muscle spasticity

Approved in European Union as Zanaflex for:

• Muscle spasticity

Approved in Canada as Zanaflex for:

• Muscle spasticity

Approved in Japan as Zanaflex for:

• Muscle spasticity

Who Is Running the Clinical Trial?

NorthShore University HealthSystem

Lead Sponsor

Trials

134

Recruited

740,000+

Endeavor Health

Lead Sponsor

Trials

135

Recruited

742,000+

Published Research Related to This Trial

A case of complete urinary retention was linked to a herpes zoster virus (HZV) neurogenic bladder, highlighting a rare but significant complication of HZV infection.

The study discusses various aspects of the disease, including urodynamics and the underlying physiological mechanisms, which are important for understanding how HZV can affect bladder function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Complete urinary retention secondary to lumbosacral zona]. Punga, A., Zemrag, J., Galas, JM., et al.[2006]

Atropa belladonna L. and its active compound atropine were found to induce urinary retention in rats, indicating a significant pharmacological effect.

The study suggests that Atropa belladonna is more effective in causing urinary retention than previously anticipated based on its alkaloid content, highlighting the need for further investigation into its mechanisms of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparative study of Atropa belladonna and atropine on an animal model of urinary retention. Tita, B., Bolle, P., Martinoli, L., et al.[2019]

In a study of 40 children with dysfunctional voiding, tizanidine demonstrated significant improvements in nocturnal enuresis, urgency attacks, and daytime incontinence compared to baseline, indicating its efficacy as a treatment option.

Both tizanidine and doxazosin showed similar overall improvements in symptoms, but tizanidine had a better profile for reducing specific voiding issues, with a low incidence of adverse effects (15% overall), suggesting it is a safe treatment for children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Doxazosin versus tizanidine for treatment of dysfunctional voiding in children: a prospective randomized open-labeled trial. El-Hefnawy, AS., Helmy, T., El-Assmy, MM., et al.[2014]

Tolterodine, a muscarinic receptor antagonist, is the gold standard for treating storage lower urinary tract symptoms (LUTS) in men, offering a better efficacy and adverse event profile compared to earlier antimuscarinics, which often caused issues like dry mouth and cognitive dysfunction.

The extended release (ER) formulation of tolterodine (4 mg once daily) is as effective as the intermediate release (IR) formulation (2 mg twice daily) but has fewer side effects, and combining tolterodine with an alpha-blocker significantly improves treatment efficacy without increasing the risk of acute urinary retention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolterodine in the Treatment of Male LUTS. Gacci, M., Sebastianelli, A., Salvi, M., et al.[2018]

A 57-year-old immunosuppressed male developed urinary retention after a shingles outbreak, highlighting a rare complication of herpes zoster linked to viral infection in the sacral area.

After receiving antiviral and corticosteroid treatment, the patient fully recovered bladder function within 6 weeks, indicating that timely medical intervention can effectively address this complication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Herpes-zoster associated urinary retention in a 57-year-old immunocompromised male. Au, VH., Kazi, A., Bruha, M., et al.[2020]

Two cases of acute urinary retention in Chinese patients were linked to reactivation of sacral herpes zoster, highlighting a rare complication of this viral infection.

Treatment involved indwelling urinary catheterization, antiviral medication (ganciclovir), and physiotherapy with infrared light, which successfully restored the micturition reflex in both patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Herpes zoster-induced acute urinary retention: Two cases and literature review. He, H., Tang, C., Yi, X., et al.[2018]

Long-term use of terazosin, an alpha-blocker, in two children with Hinman's syndrome showed no significant side effects, indicating its safety for treating non-neurogenic bladder dysfunction.

Both children experienced improvement in urgency symptoms and resolution of secondary enuresis, suggesting that terazosin, combined with other therapies, can effectively manage bladder dysfunction and may have lasting benefits even after treatment is stopped.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use and rationale of selective alpha blockade in children with non-neurogenic neurogenic bladder dysfunction. Bogaert, G., Beckers, G., Lombaerts, R.[2019]

In a study of 100 women aged 20 to 70 with lower urinary tract symptoms, terazosin was found to be significantly more effective than placebo, with 80% of terazosin users achieving a quality of life score of 2 or less compared to 55% of placebo users.

Terazosin also led to significant improvements in specific symptoms like frequency and straining, and while there were some adverse events, they were not significantly different from those experienced by the placebo group, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Terazosin therapy for patients with female lower urinary tract symptoms: a randomized, double-blind, placebo controlled trial. Low, BY., Liong, ML., Yuen, KH., et al.[2013]

A case report of a 26-year-old man revealed that acute urinary retention can occur after brief methamphetamine use, highlighting the need for awareness of drug-related causes in younger patients presenting with urinary issues.

The patient experienced significant improvement after catheterization and discontinuation of methamphetamine, suggesting that addressing drug use is crucial in managing urinary retention effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Urinary retention concomitant with methamphetamine use: a case report. Ojo, AO., Ajasa, AL., Oladipupo, RB., et al.[2021]

In a study of 60 men over 50 years old with acute urinary retention (AUR) due to benign prostatic hyperplasia (BPH), silodosin significantly improved the success rate of trial without catheter (TWOC) to 76.7%, compared to 36.7% in the placebo group.

Silodosin was found to be safe, with no reported adverse effects, and it reduced the odds of TWOC failure, indicating its efficacy in managing AUR related to BPH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective randomized placebo-controlled study to assess the safety and efficacy of silodosin in the management of acute urinary retention. Kumar, S., Tiwari, DP., Ganesamoni, R., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06258785

Effect of Tizanidine on Postoperative Urinary Retention ... Tizanidine is a low-risk, well tolerated, cost-effective medication. No study to date has evaluated preoperative administration of tizanidine for postoperative ...

2. clinicaltrial.be clinicaltrial.be/en/details/459385?per_page=20&only_recruiting=0&only_eligible=0&only_active=0

Effect of Tizanidine on Postoperative Urinary Retention A... Tizanidine is a muscle relaxant which can work to alleviate this spasm and, theoretically, prevent postoperative urinary retention. Tizanidine ...

3. withpower.com withpower.com/trial/phase-3-reconstructive-pelvic-surgery-3-2024-a0e05

Tizanidine for Urinary Retention Tizanidine is a muscle relaxant which can work to alleviate this spasm and, theoretically, prevent postoperative urinary retention.

4. goldjournal.net goldjournal.net/article/S0090-4295(11)02579-9/abstract

Doxazosin Versus Tizanidine for Treatment of ... Tizanidine could be a safe and effective treatment of children with dysfunctional voiding due to pelvic floor/skeletal sphincter dysfunction.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4524377/

Tizanidine-induced acute severe cystitis in a female taking ... We report a case of a 26-year-old Asian female on famotidine who presented with acute severe urinary burning after taking tizanidine.

6. go.drugbank.com go.drugbank.com/drugs/DB00697

Tizanidine: Uses, Interactions, Mechanism of Action Improve decision support & research outcomes with our structured adverse effects data. ... Postoperative Urinary Retention (POUR) / Reconstructive Pelvic Surgery ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2006/020397s021,021447s002lbl.pdf

PRESCRIBING INFORMATION Zanaflex Capsules™ 1 ... Tizanidine is a short-acting drug for the management of spasticity. Because of the. 203 short duration of effect, treatment with tizanidine should be reserved ...

8. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK519505/

Tizanidine - StatPearls - NCBI Bookshelf Tizanidine is an FDA-approved drug for managing spasticity. It is a centrally acting alpha-2 receptor agonist. Tizanidine effectively works with spasticity ...