RATIONALE FOR THE PHASE II CLINICAL TRIAL ASSESSING THE SAFETY, TOLERABILITY, AND EFFICACY OF LENALIDOMIDE IN MILD COGNITIVE IMPAIRMENT DUE TO ALZHEIMER’S DISEASE
- Marwan Sabbagh, United States of America
Abstract
Aims
Accumulating evidence indicates that NF-kappa B, TNFα, interleukins (IL-1beta, IL-2, and IL-6), and chemokines (IL-8) are elevated in the blood and central nervous system of AD patients suggestng that inflammation plays a central role in the cause and effect of AD neuropathology. The immunomodulator, anti-cancer agent lenalidomide is a pleiotropic agent that both lowers the expression of TNFα, IL-6, IL-8, and increases the expression of anti-inflammatory cytokines (e.g. IL-10), to modulate both innate and adaptive immune responses. We aim to test the central hypothesis that lenalidomide reduces inflammatory and AD-associated pathological biomarkers, and improves cognition.
Methods
For this, we designed an 18-month, Phase II, double-blind, randomized, placebo controlled, and proof-of-mechanism clinical study in amnestic mild cognitive impairment due to AD; aMCI). The effects of lenalidomide treatment will be assessed after 12 months of treatment and 6 months washout (month 18). The primary aim: to assess the effect of lenalidomide on cognition after 12 months of treatment. The secondary aim is to assess the safety and tolerability of lenalidomide in aMCI patients. The tertiary and exploratory aims: We will investigate the potential of blood inflammatory markers as surrogate markers of the therapeutic efficacy of the study drug.Lenalidomide 10 mg/day vs. placebo taken daily orally (ratio 1:1) in 30 subjects with aMCI due to AD. Age range 50-90 with standard I/E criteria
Results
baseline data and rationale will be presented
Conclusions
Our study should determine whether lenalidomide is safe in AD subjects and whether it can alter the clinical progression of AD when administered before dementia onset