The Neuromuscular Junction: A Shared Vulnerability in Aging and Disease.
Kathryn R Moss, Fereshteh B Darvishi, Yomna Badawi...
https://pubmed.ncbi.nlm.nih.gov/41224659Actively Recruiting
Phase 2
Age: 18Years - 85Years
All Genders
ID06249867
A Randomized, Double-blind, Phase 2 Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of 15 mg Darifenacin Daily in Patients With Amyotrophic Lateral Sclerosis
Led by Oliver Blanchard · Updated on 2025-09-05
30
Participants Needed
2
Research Sites
4 weeks
Total Duration
On this page
Sponsors
O
Oliver Blanchard
Lead Sponsor
U
Université de Montréal
Collaborating Sponsor
AI-Summary
What this Trial Is About
Amyotrophic lateral sclerosis (ALS) is a progressive neurological disease that causes the death of motor neurons, leading to severe disability and often fatal outcomes. A key early feature of ALS is the loss of connection at neuromuscular junctions (NMJs), where specialized glial cells called Perisynaptic Schwann Cells (PSCs) normally help maintain and repair these connections. Research suggests that reducing activity of muscarinic acetylcholine receptors (mAChRs) on PSCs may restore their ability to repair NMJs, which could improve function and quality of life for ALS patients. This Phase 2 trial aims to test the safety, tolerability, and effects of the drug Darifenacin, a selective M3 muscarinic receptor antagonist, in adults with ALS. Participants will be randomly assigned to receive either Darifenacin or a placebo in a double-blind manner. The treatment begins with a two-week titration period where patients take 7.5 mg daily, followed by 22 weeks at an increased dose of 15 mg daily (two 7.5 mg tablets). Depending on individual response, dose adjustments or temporary stops may occur for safety reasons. The study evaluates how Darifenacin impacts patient safety, muscle strength, neurological function, depression levels, and NMJ innervation. Throughout the 24-week trial, patients will attend regular clinical assessments to monitor their physical and neurological status, muscle strength, and other health measures including depression and respiratory function. Researchers will track outcomes such as safety and tolerability, pharmacokinetics, and functional rating scales specific to ALS. Optional muscle biopsies may be performed with additional safety precautions. The total participation spans approximately six months, with close monitoring to evaluate the drug's impact on ALS progression and patient well-being.
CONDITIONS
Brief Title
A Study to Assess the Safety, Tolerability, and Pharmacology of Darifenacin in Patients With ALS
Who Can Participate
Age: 18Years - 85Years
All Genders
Eligibility Criteria
You may qualify if you...
- Able to understand and willing to sign informed consent.
- Male or female aged 18 to 85 years at consent.
- Confirmed diagnosis of familial or sporadic ALS by established criteria.
- ALS symptoms started less than 36 months ago.
- Forced Vital Capacity (FVC) of 50% or higher.
- Able to swallow tablets without crushing.
- Female participants must not be breastfeeding, have a negative pregnancy test, not intend to become pregnant, and agree to use contraception during the study.
- Male participants with partners who may become pregnant must agree to use reliable birth control and avoid donating sperm during the study.
- On stable dosing of standard ALS treatments (Riluzole, Edaravone, Albrioza) for at least 30 days before randomization.
- For optional biopsy, normal platelet or coagulation tests and ability to abstain from anticoagulants as directed.
You will not qualify if you...
- Untreated or uncontrolled narrow-angle glaucoma, gastric retention, urinary retention, or liver disease.
- History of severe allergic reactions to antimuscarinic drugs.
- Diagnosis of other neurodegenerative diseases such as Multiple Sclerosis, Parkinson's, Myasthenia Gravis, or Alzheimer's disease.
- Severe liver impairment or abnormal liver enzymes.
- History or positive test for hepatitis B or C.
- Any medical condition posing added risk or interfering with trial participation.
- Currently enrolled in another clinical trial with investigational treatment.
- Treatment with investigational drugs within 1 month before study.
- Previous treatment with darifenacin.
- History of drug or alcohol abuse.
- Pregnant, breastfeeding, or intending to conceive during study.
- Abnormal ECG placing participant at risk.
- Use of strong CYP3A4 inducers or inhibitors or certain CYP2D6 substrates.
- Botulinum injections within past 6 months.
- Use of antimuscarinic medications for overactive bladder within 30 days prior.
- For biopsy participants, use of anticoagulants or bleeding risks including anatomical abnormalities or abnormal coagulation tests.
AI-Screening
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Your Study Journey
Screening
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Treatment
Duration - 24 weeks
Participants receive daily doses of either darifenacin or placebo tablets. The first 2 weeks serve as a titration period with a lower dose, followed by 22 weeks of increased dose or matching placebo.
Regular clinical assessments at scheduled visits during treatment
Trial Site Locations
Total: 2 locations
1
Ottawa Hospital Research Institute
Ottawa, Ontario, Canada, K1Y 4E9
Actively Recruiting
2
Montreal Neurological Institute
Montreal, Quebec, Canada, H3A 2B4
Actively Recruiting
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Research Team
N
Nisha Pulimood, PhD
G
Gabriele Riva, PhD
How is the study designed?
Study Type
INTERVENTIONAL
Masking
QUADRUPLE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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