Repurposing Siponimod for Alzheimer's Disease
Eligible age
50–85 yrs
Accepts
All genders
Locations
1 state
Healthy volunteers
No
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About this study
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.
Sponsor: St. Joseph's Hospital and Medical Center, Phoenix
You may qualify if…
- ✓ 1. Male or female at least 50 years of age, but less than 85 (84 at time of screening)
- ✓ 2. Females must be of non-childbearing potential or have negative pregnancy test at time of screening. Women of non-childbearing potential are defined as women who are either permanently sterilized (hysterectomy, bilateral oophorectomy or bilateral salpingectomy) or who are postmenopausal. Women will be considered postmenopausal if they have been amenorrheic for \>12 months prior to the planned date of enrollment.
- ✓ 3. Must have a diagnosis of mild Alzheimer's Dementia determined by medical record review.
- ✓ 4. Vision and hearing must be sufficient to comply with study procedures.
- ✓ 5. Be able to take oral medications.
- ✓ 6. Must be able to attend all study visits indicated in the schedule of visits.
- ✓ 7. Must have a collateral informant/study partner who has significant direct contact with the patient at least 10 hours per week and who is willing to accompany the patient to specified clinic visits, supervise administration of all study medication, and be available for telephone visits/interviews.
- ✓ 8. Documented Mini Mental State Exam (MMSE) score between 20-26 at Screening Visit Day 1.
You may not qualify if…
- ✕ 1. Taking one of the following medications: Medications for treatment of cancer or other drugs that weaken the immune system (ex. Natalizumab and Rituximab), Amiodarone, Bishydroxycoumarin, Chloramphenicol, Cimetidine, Fluconazole, Fluvastatin, Miconazole, Phenylbutazone, Sulphinpyrazone, Sulphadiazine, Sulphamethizole, Sulfamethoxazole, Sulphaphenazole, Trimethoprim, and Zafirlukast.
- ✕ 2. Current active infection in participants including, but not limited to, herpes zoster, herpes infection, bronchitis, sinusitis, upper respiratory infection and fungal skin infection. Siponimod may increase the risk in participants with active infections.
- ✕ 3. If participant received mRNA COVID-19 vaccination, must have received last dose at least 3 months prior to first dose of study drug/placebo.
- ✕ 4. Current evidence or history within the last 3 years of a neurological or psychiatric illness that could contribute to dementia, including (but not limited to) epilepsy, focal brain lesion, Parkinson's disease, seizure disorder, or head injury with loss of consciousness.
- ✕ 5. Meets DSM IV criteria for any major psychiatric disorder including psychosis, major depression and bipolar disorder.
- ✕ 6. Known history of or self-reported active alcohol and/ or substance abuse within the past three years.
- ✕ 7. Isolated living circumstances which would prohibit a study partner from providing sufficient and credible information about the participant.
- ✕ 8. Poorly controlled hypertension
Where it's recruiting
Phoenix
Source: ClinicalTrials.gov · NCT06639282 · last updated 2026-03-04