NCT06249867
A Study to Assess the Safety, Tolerability, and Pharmacology of Darifenacin in Patients With ALS
Recruiting · Phase 2 · Oliver Blanchard · registry updated 2026-10-09
Inclusion and exclusion lines below are quoted from ClinicalTrials.gov. No match score is shown, because a score needs a person's age, biomarkers, and treatment dates. Confirm the record with the study team.
Amyotrophic lateral sclerosis (ALS) is a progressive neurological disorder characterized by selective death of upper and lower motor neurons, which leads to severe disability and fatal outcomes. One of the major hallmarks of ALS is the denervation of neuromuscular junctions (NMJs), which is one of the earliest events seen in ALS patients and mouse models of ALS. Under healthy conditions, glial cells called Perisynaptic Schwann Cells (PSCs) have a key role in regulating the stability and maintenance of NMJs, but they only participate in NMJ repair once denervation occurs. Denervation and the subsequent decline in synaptic activity triggers a loss of muscarinic acetylcholine receptors (mAChRs) in the PSC, and the resulting decrease in mAChR-mediated gene expression drives the "repair mode" of the PSC. In assessing the NMJ under conditions of ALS, a scarcity of process extensions in PSCs was observed for months prior to disease onset in the superoxide dismutase 1 (SOD1) mouse model of ALS, indicating inadequate glial repair. Collectively, these preclinical findings support the hypothesis that dampening glial mAChRs will restore the anticipated "repair" response of PSCs in the NMJ....
Inclusion
- Able to comprehend and willing to sign an Informed Consent Form (ICF).
- Male or female, ≥ 18 years old and ≤85 years old, at the time of signing the ICF.
- Confirmed diagnosis of familial or sporadic ALS, defined as meeting the probable, laboratory-supported probable, or definite criteria for a diagnosis of ALS according to the World Federation of Neurology Modified El Escorial criteria (1).
- ALS duration of less than 36 months from the symptom onset.
- FVC of ≥ 50 %.
- Able to swallow tablets without crushing.
Exclusion
- Patients with, or at risk for, the following conditions:
- Untreated or uncontrolled narrow-angle glaucoma;
- Gastric retention
- Urinary retention
- Liver disease
- Patients with a known history of severe allergic or anaphylactic reactions to antimuscarinic medications