Actively Recruiting
Repurposing Siponimod for Alzheimer's Disease
Led by St. Joseph's Hospital and Medical Center, Phoenix · Updated on 2026-03-04
105
Participants Needed
1
Research Sites
213 weeks
Total Duration
On this page
Sponsors
S
St. Joseph's Hospital and Medical Center, Phoenix
Lead Sponsor
T
Texas Tech University Health Sciences Center
Collaborating Sponsor
AI-Summary
What this Trial Is About
Collaboration with multiple sclerosis (MS) specialty colleagues led us to formulate the central hypothesis that Siponimod could lower the rate of brain atrophy in Alzheimer's disease (AD) subjects. To test our central hypothesis, we will carry out an 18-month Phase II, double-blind, randomized, twoarmed, placebo controlled, proof-of-concept clinical study in early AD subjects (i.e. mild AD) who will be receiving an escalating dose of Siponimod or placebo in the ratio 2:1 for 12 months, followed by a 6-month washout period. The primary outcome measures are safety and tolerability of Siponimod in mild AD subjects. The secondary outcome measures are the rates of brain atrophy derived from volumetric MRI (vMRI) as a proxy for neurodegeneration conducted at baseline, 6, 12, and 18 months. The tertiary outcome measures are the changes in cognition and the levels of AD-associated (e.g., Aβ and tau) and inflammatory biomarkers in CSF after Siponimod exposure. In an exploratory effort, we will also measure plasma inflammatory markers during the entire duration of the study to investigate whether one or more of these markers can be used as dynamic surrogate markers of treatment response. Using our unique experience with the repurposing of immunomodulatory drugs for AD (and NCT #04032626), in the present project we are using elements of clinical trial design that we believe were successful and made some adjustments to fit the pharmacologic and toxic properties of Siponimod.
CONDITIONS
Official Title
Repurposing Siponimod for Alzheimer's Disease
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Male or female aged 50 to less than 85 years at screening
- Females must be of non-childbearing potential or have a negative pregnancy test at screening
- Diagnosis of mild Alzheimer's dementia confirmed by medical records
- Sufficient vision and hearing to comply with study procedures
- Ability to take oral medications
- Willingness and ability to attend all study visits
- Have a study partner who has significant contact (at least 10 hours/week) and can assist with visits and medication
- Mini Mental State Exam (MMSE) score between 20 and 26 at screening
- Brain CT or MRI within 12 months before screening showing no significant lesions
- Hachinski ischemic score less than 4
- Geriatric depression scale less than 10
- Proof of prior varicella immunization (VZV IgG)
- Capacity to provide informed consent or have a legally authorized representative
- No active suicidality on Columbia-Suicide Severity Rating Scale
- Stable prostate cancer allowed at discretion of Medical Monitor
- On or previously on monoclonal antibody treatment for Alzheimer's for more than 6 months allowed if other criteria met
You will not qualify if you...
- Taking certain medications including cancer treatments, immune suppressants, amiodarone, and others listed
- Current active infections such as herpes, bronchitis, sinusitis, or fungal skin infections
- Received mRNA COVID-19 vaccination within 3 months prior to first dose
- History or current neurological or psychiatric illness contributing to dementia within last 3 years
- Major psychiatric disorders including psychosis, major depression, bipolar disorder
- Active alcohol or substance abuse within past 3 years
- Living alone without a study partner able to provide information
- Poorly controlled hypertension
- Known heart block or recent heart attack within last year
- Severe pulmonary disease requiring frequent hospitalization
- Untreated obstructive sleep apnea
- Thyroid disease unless stable on treatment for at least 6 months
- Active cancer within 5 years except non-melanoma skin tumors
- Low lymphocyte or neutrophil counts or history of such
- History or current blood clots
- Significant liver or kidney disease
- Blood disorders such as unexplained anemia or low platelet count
- Use of investigational drugs within 30 days or five half-lives
- Unwilling or unable to undergo CT or MRI imaging
- Investigator judgment that participation is not in participant's best interest
- Specific genetic profile CYP2C9*3/*3 genotype
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 1 location
1
St. Joseph's Hospital and Medical Center
Phoenix, Arizona, United States, 85013
Actively Recruiting
Research Team
M
Marwan N Sabbagh, MD
CONTACT
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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