Neurodegenerative Alzheimer's Disease and Amyotrophic Lateral Sclerosis (NADALS) Basket Trial
United States17 participantsStarted 2022-12-05
Plain-language 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.
Who can participate
Age range18 Years – 90 Years
SexALL
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Inclusion criteria
✓. Must be 55-90 years old, inclusive and have one of the following:
✓. Screening CSF level of CCL2 level ≥ 250 pg/mL
✓. Up-to-date immunization records per CDC guidelines
✓. Must have received the Recombinant Zoster Vaccine (RZV, also known as Shingrix) within 4 years prior to enrollment. Note: Only one dose of RZV is needed prior to the Baseline Visit.
✓. Must be fully vaccinated for COVID-19 per CDC guidelines
✓. For participants with ALS:
Exclusion criteria
✕. Ability to medically undergo LP in the opinion of the investigator (e.g., no bleeding disorder, allergy to local anesthetics, prior lumbar surgery which might make LP difficult, a skin infection at or near the LP site, evidence of high intracranial pressure, or anticipated difficulty getting into position for LP).
✕. Capable of providing informed consent and following study procedures.
✕
What they're measuring
1
CSF Concentration of baricitinib
Timeframe: Measured at baseline, 8 weeks and 16 weeks, results reported at the completion of the study
2
CSF CCL2 Concentration
Timeframe: Measured at baseline, 8 weeks and 16 weeks, results reported at the completion of the study
. Women who are pregnant, breastfeeding, or planning to become pregnant during the trial
✕. Any unstable clinically significant medical condition other than ALS or AD (e.g., within six months of baseline, including but not limited to myocardial infarction, angina pectoris, congestive heart failure, or neoplasm undergoing active treatment).
✕. Active cancer or history of cancer, except for the following: basal cell carcinoma, cervical carcinoma in situ, prostatic carcinoma in situ, or other malignancies curatively treated and with no evidence of disease recurrence for at least 5 years. Active cancer includes cancers with current disease manifestations or therapy that could adversely affect participant safety and longevity, create the potential for drug-drug interactions, or compromise the interpretation of study results.
✕. History of diverticulitis or bowel perforation.
✕. Active ulcerative colitis, Crohn's disease, and history of peptic ulcer disease within the past 5 years or after the age of 65.
✕. Active, serious infection, including localized infection in the opinion of the investigator.