BENITIONSClinical Trial Intelligence

Neurodegenerative Alzheimer's Disease and Amyotrophic Lateral Sclerosis (NADALS) Basket Trial

Phase 1/2 Completed NCT05189106

ConditionAmyotrophic Lateral Sclerosis, Alzheimer Disease, Mild Cognitive Impairment
PhasePhase 1/2
SponsorMassachusetts General Hospital
StatusCompleted
Enrollment17 participants
InterventionsBaricitinib
Start dateDec 5, 2022
Completion dateApr 24, 2025
Results postedJun 30, 2026

Summary

This is an open-label, biomarker-driven basket trial of baricitinib in people with subjective cognitive disorder, mild cognitive impairment, Alzheimer's disease (AD), Amyotrophic lateral sclerosis (ALS), or asymptomatic carriers of an ALS-related gene, such as a hexanucleotide expansion in the C9ORF72 gene, with evidence of abnormal inflammatory signaling in cerebrospinal fluid (CSF) at baseline. Each participant will be treated with baricitinib for 24 weeks; no placebo will be given. Participants will receive baricitinib 2 mg per day by mouth for the first 8 weeks and baricitinib 4 mg per day by mouth for the remaining 16 weeks. This proof of concept trial will ascertain whether baricitinib at 2 mg per day, 4 mg per day, or both reaches therapeutic levels in the CSF and suppresses inflammatory biomarkers associated with type I interferon signaling among the study participants.

CSF Concentration of Baricitinib

Measured at baseline, 8 weeks from baseline, and 16 weeks from baseline. Results reported at the completion of the study. · nmol/L

Participants With Alzheimer's Disease (AD)1.244 ± 0.301 nmol/L
Participants With Amyotrophic Lateral Sclerosis (ALS)1.748 ± 0.282 nmol/L
Participants That Are an Asymptomatic Gene Carrier (AGC) for an ALS-causative Gene0.460 ± 0.797 nmol/L
Participants With Alzheimer's Disease (AD)2.469 ± 0.464 nmol/L
Participants With Amyotrophic Lateral Sclerosis (ALS)3.804 ± 0.489 nmol/L
Participants That Are an Asymptomatic Gene Carrier (AGC) for an ALS-causative Gene1.965 ± 1.228 nmol/L

CSF CCL2 Concentration

Measured at baseline, 8 weeks from baseline, and 16 weeks from baseline. Results reported at the completion of the study. · pg/mL

Participants With Alzheimer's Disease (AD)417.640 pg/mL
Participants With Amyotrophic Lateral Sclerosis (ALS)465.868 pg/mL
Participants That Are an Asymptomatic Gene Carrier (AGC) for an ALS-causative Gene501.728 pg/mL
Participants With Alzheimer's Disease (AD)407.202 pg/mL
Participants With Amyotrophic Lateral Sclerosis (ALS)473.487 pg/mL
Participants That Are an Asymptomatic Gene Carrier (AGC) for an ALS-causative Gene503.127 pg/mL

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