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

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.

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis; Lower Urinary Tract Symptoms; Urinary Retention; Voiding Dysfunction; Dysuria
• Intervention / Treatment: Drug: Tamsulosin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Stéphane DROUPY; Phone Number: 04.66.68.32.30; Email: stephane.droupy@chu-nimes.fr

Study Locations

• France
  • Nîmes, France
    • Recruiting
    • CHU de Nîmes
    • Sub-Investigator: Eric Thouvenot
    • Sub-Investigator: Giovanni Castelnovo
    • Sub-Investigator: Kamel Ben Naoum
    • Contact: Anissa Megzari; Phone Number: 04.66.68.42.36; Email: drc@chu-nimes.fr
    • Principal Investigator: Stephane DROUPY

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nīmes
• Investigators: Principal Investigator: Stéphane DROUPY, CHU de Nîmes

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2022
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: June 27, 2022
• First Submitted That Met QC Criteria: June 27, 2022
• First Posted (Actual): June 30, 2022

Study Record Updates

• Last Update Posted (Actual): June 25, 2024
• Last Update Submitted That Met QC Criteria: June 24, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Urologic Diseases; Urological Manifestations; Urination Disorders; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Multiple Sclerosis; Sclerosis; Lower Urinary Tract Symptoms; Urinary Retention; Dysuria; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Urological Agents; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Tamsulosin
• Other Study ID Numbers: NIMAO/2021-1/EB-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No