Efficacy of Alpha-blockers (Tamsulosin) in the Treatment of Symptomatic Dysuria in Multiple Sclerosis in Women

Study Overview
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Brief Summary
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Multiple sclerosis (MS) is the leading non-traumatic cause of severe acquired disability in young people. The disease is defined by relapses, which can affect all neurological functions depending on the location of the new inflammatory lesion(s). The disease can thus manifest itself through bladder and bowel disorders (BWS), which affect approximately 80% of MS patients in all stages. Lower urinary tract dysfunction has a significant negative impact on the quality of life of patients and places a significant burden on the healthcare system in terms of resource allocation. In addition, there is a risk of long-term chronic renal failure, an infectious risk (recurrent cystitis and/or pyelonephritis, sometimes life-threatening) and a lithiasis risk. The most frequently observed urinary symptoms are: urinary frequency, urgency with or without urinary incontinence, dysuria and chronic retention of urine. These disorders most often combine bladder hyperactivity and dysuria. This dysuria may be responsible for recurrent urinary tract infections, lithiasis, alteration of renal function. The only therapeutic class currently used to treat dysuria in MS is alpha-blockers. Tamsulosin, alfusozin and doxazosin induce relaxation of the urethral smooth sphincter and prostatic urethral muscle fibers, facilitating the removal of subvesical obstruction and bladder emptying. The study investigators hypothesize that treatment with tamsulosin 0.4 mg daily in adult MS patients with dysuria will result in symptom improvement as assessed by the International Prostate Symptom Score (IPSS) and Urinary Symptom Profile (USP) scores, a decrease in post-void residual, and an improvement in urine flow and quality of life.

Official Title
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Efficacy of Alpha-blockers (Tamsulosin) in the Treatment of Symptomatic Dysuria in Multiple Sclerosis in Women

Conditions
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Multiple Sclerosis, Dysuria, Lower Urinary Tract Symptoms, Voiding Dysfunction, Urinary Retention

Intervention / Treatment
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* Drug: Tamsulosin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient must have given their free and informed consent and signed the consent form The patient must be a member or beneficiary of a health insurance plan Patient with multiple sclerosis (EDSS score < 7.5). Moderate to severe dysuria (IPSS score > 7) due to bladder sphincter dyssynergia confirmed by complete urodynamic workup. Patient under stable treatment. Exclusion Criteria: The subject is participating in another category 1 interventional study, or a trial involving a non-CE marked or CE marked off-label medical device or is in a period of exclusion determined by a previous study The subject refuses to sign the consent It is impossible to give the subject informed information The patient is under safeguard of justice or state guardianship Hypersensitivity to tamsulosin hydrochloride, including angioedema induced by the drug or any of the excipients. History of orthostatic hypotension. Severe hepatic impairment. Concomitant treatment with diclofenac, warfarin, CYP3A4 inhibitors. - Patient with complete urinary retention at the time of the pre-inclusion consultation, requiring management by intermittent self-catheterization or, failing that, an indwelling bladder catheter from the outset. Major medical or psychiatric illness that, in the opinion of the investigator, would place the subject at risk or could compromise compliance with the study protocol. Presence of another neurological pathology (excluding MS). Swallowing problems that compromise oral medication. Scheduled cataract surgery within 4 months. Pregnant, parturient or breastfeeding patient.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: One month of intervention of drug or placebo followed by one month wash-out period and then final one month intervention with the remaining treatment not received in the first cycle.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tamsulosin<br> | Drug: Tamsulosin<br>* One 0.4mg Tamsulosin capsule taken per day for 30 days<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* one placebo capsule per day for 30 days. with identical appearance (color and size) to the experimental drug, composed of microcrystalline cellulose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary symptoms between groups | Measured using the International Prostate Symptom Scale (IPSS), scoring ranging from 0-35 | Start of first intervention phase (Day 0) | 
| Urinary symptoms between groups | Measured using the International Prostate Symptom Scale (IPSS), scoring ranging from 0-35 | End of first intervention phase (Day 30) | 
| Urinary symptoms between groups | Measured using the International Prostate Symptom Scale (IPSS), scoring ranging from 0-35 | Start of first intervention phase (Day 60) | 
| Urinary symptoms between groups | Measured using the International Prostate Symptom Scale (IPSS), scoring ranging from 0-35 | End of first intervention phase (Day 90) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary symptoms between groups | Measured using the Urinary Symptom Profile (USP) questionnaire: score ranging from 0-39 | Start of first intervention phase (Day 0) | 
| Urinary symptoms between groups | Measured using the Urinary Symptom Profile (USP) questionnaire: score ranging from 0-39 | End of first intervention phase (Day 30) | 
| Urinary symptoms between groups | Measured using the Urinary Symptom Profile (USP) questionnaire: score ranging from 0-39 | Start of first intervention phase (Day 60) | 
| Urinary symptoms between groups | Measured using the Urinary Symptom Profile (USP) questionnaire: score ranging from 0-39 | End of first intervention phase (Day 90) | 
| Post-mictional residue between groups | ml, measured with BladderScan | Start of first intervention phase (Day 0) | 
| Post-mictional residue between groups | ml, measured with BladderScan | End of first intervention phase (Day 30) | 
| Post-mictional residue between groups | ml, measured with BladderScan | Start of first intervention phase (Day 60) | 
| Post-mictional residue between groups | ml, measured with BladderScan | End of first intervention phase (Day 90) | 
| Maximum urine flow rate between groups | ml/s | Start of first intervention phase (Day 0) | 
| Maximum urine flow rate between groups | ml/s | End of first intervention phase (Day 30) | 
| Maximum urine flow rate between groups | ml/s | Start of first intervention phase (Day 60) | 
| Maximum urine flow rate between groups | ml/s | End of first intervention phase (Day 90) | 
| Quality of life linked to urinary dysfunction between groups | Qualiveen-30 questionnaire; score 0-4 | Start of first intervention phase (Day 0) | 
| Quality of life linked to urinary dysfunction between groups | Qualiveen-30 questionnaire; score 0-4 | End of first intervention phase (Day 30) | 
| Quality of life linked to urinary dysfunction between groups | Qualiveen-30 questionnaire; score 0-4 | Start of first intervention phase (Day 60) | 
| Quality of life linked to urinary dysfunction between groups | Qualiveen-30 questionnaire; score 0-4 | End of first intervention phase (Day 90) | 
| Quality of life between groups | EQ-5D questionnaire; score 0-100 | Start of first intervention phase (Day 0) | 
| Quality of life between groups | EQ-5D questionnaire; score 0-100 | End of first intervention phase (Day 30) | 
| Quality of life between groups | EQ-5D questionnaire; score 0-100 | Start of first intervention phase (Day 60) | 
| Quality of life between groups | EQ-5D questionnaire; score 0-100 | End of first intervention phase (Day 90) | 
| Fatigue between groups | Modified Fatigue Impact Scale; score 0-84 | Start of first intervention phase (Day 0) | 
| Fatigue between groups | Modified Fatigue Impact Scale; score 0-84 | End of first intervention phase (Day 30) | 
| Fatigue between groups | Modified Fatigue Impact Scale; score 0-84 | Start of first intervention phase (Day 60) | 
| Fatigue between groups | Modified Fatigue Impact Scale; score 0-84 | End of first intervention phase (Day 90) | 
| Drug safety | Yes/no occurence of the following adverse events: headache, asthenia, gastrointestinal disorders, orthostatic hypotension | End of first intervention phase (Day 30) | 
| Drug safety | Yes/no occurence of the following adverse events: headache, asthenia, gastrointestinal disorders, orthostatic hypotension | End of first intervention phase (Day 90) |