Ignite Creation Date:
2024-10-26 @ 3:42 PM
Last Modification Date:
2024-10-26 @ 3:42 PM
Study NCT ID:
NCT06639282
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-10-09
Brief Title:
Repurposing Siponimod for Alzheimers Disease
Sponsor:
None
Organization:
None
Study Overview
Official Title:
SIPO1-AD a Phase II Clinical Trial for the Assessment of Safety Tolerability and Efficacy of Siponimod in Patients with Mild Alzheimeramp39s Disease Dementia
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
SIPO1-AD
Brief Summary:
Collaboration with multiple sclerosis MS specialty colleagues led us to formulate the central hypothesis that Siponimod could lower the rate of brain atrophy in Alzheimers 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 ie mild AD who will be receiving an escalating dose of Siponimod or placebo in the ratio 21 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 eg 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
Detailed Description:
Alzheimers disease AD is a neurodegenerative disorder with several complex neuropathologies suspected to develop sequentially but that overlap over time as symptoms progress to dementia Thus to be effective future intervention strategies will likely require combination therapies or pleiotropic agents to tackle several AD molecular pathogenic pathways simultaneously For more than a decade our group has been exploring the repurposing of immunomodulators for AD Recent discussions with collaborators who specialize in multiple sclerosis suggest that sphingosine-1-phosphate receptor S1PR modulators are strong candidates for repurposing in AD Indeed S1PR modulators are blood brain barrier BBB penetrant and display pleiotropic actions including immunomodulation and neuroprotective properties S1P is a versatile endogenous molecule that regulates several signaling pathways by binding to five G-protein-coupled receptors which are expressed in high levels in cardiac vascular immune and brain cells This widespread localization of S1PR was the historical basis for Novartis Pharmaceuticals Inc to develop oral formulations of S1PR modulators for multiple sclerosis MS which proved successful and resulted in two marketed oral compounds ie fingolimod and Siponimod In the present project we intend to collaborate with Novartis to use the most recently FDA-approved S1PR modulator Siponimod Based on MS and animal experimentation literature we hypothesize that Siponimod could alter the rate of neurodegeneration as measured by lowering the rate of brain atrophy in mild AD dementia subjects In this Phase II proof-of-concept translational clinical study mild AD dementia subjects will be randomized 21 and will receive gradual titration regimen of Siponimod starting at 025mgday and increasing up to final dosage of 1 mgday N70 or placebo N35 for 12 months This will be followed by a 6-month washout period Siponimod has demonstrated positive immunomodulatory and neuroprotective actions in MS patients and because its toxicity profile is favorable for use in older individuals Siponimod has a strong potential to alter markers of mild AD dementia pathology and disease trajectory
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None