MCLENA-1: A Phase II Clinical Trial for the Assessment of Safety, Tolerability, and Efficacy of Lenalidomide in Patients with Mild Cognitive Impairment Due to Alzheimer’s Disease
| Autor: | Christopher Dardis, Xiaowei Zhuang, Boris Decourt, Garam Lee, Jeffrey R. Wilson, Dietmar Cordes, Marwan N. Sabbagh, Katurah Hartley, Nadia D Fulkerson, Tessa St Rose, Aaron Ritter, Frank P. DiFilippo |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Oncology
cognition medicine.medical_specialty Population lenalidomide brain imaging Neuropathology immunomodulation Article 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Dementia Pharmacology (medical) education Adverse effect Pharmacology Toxicology and Pharmaceutics (miscellaneous) Lenalidomide education.field_of_study hematologic changes business.industry biomarkers clinical trial medicine.disease cytokines 3. Good health Clinical trial Thalidomide Tolerability inflammation 030220 oncology & carcinogenesis brain amyloid business Alzheimer’s disease 030217 neurology & neurosurgery medicine.drug dementia |
| Zdroj: | Open access journal of clinical trials |
| ISSN: | 1179-1519 |
| Popis: | With the general population reaching higher ages, a surge in Alzheimer's disease (AD) incidence will happen in the coming decades, putting a heavy burden on families and healthcare systems Worldwide. This emphasizes the pressing need for AD therapeutic interventions. Accumulating evidence indicates that inflammation is prominent both in the blood and central nervous system of AD sufferers. These data suggest that systemic inflammation plays a crucial role in the cause and effects of AD neuropathology. Capitalizing on our experience from a previous clinical trial with thalidomide, we hypothesize that modulating inflammation via the pleiotropic immunomodulator lenalidomide may alter AD if administered during a proper time window in the course of the disease. Thus, in this Phase II, proof-of mechanism study, 30 amnestic mild cognitive impairment (aMCI) subjects will be treated with lenalidomide at 10 mg/day for 12 months on a 1:1 ratio, followed by a 6 months washout period. The primary objective of this study is to investigate the effect of lenalidomide on cognition, which is assessed at regular intervals. The secondary objective is to assess the safety and tolerability of lenalidomide in aMCI patients evaluated through adverse events, vital signs, clinical biochemistry, and physical and neurological examinations. Tertiary objectives are to analyze the effects of lenalidomide on brain amyloid loads (Florbetapir PET imaging) and neurodegeneration (volumetric MRI) by comparing pre- and post-dosing data. Finally, exploratory objectives will investigate whether blood inflammatory markers can serve as surrogate markers of therapeutic efficacy. 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. If effective, lenalidomide would become the first drug capable of delaying the trajectory of AD, which could lead the way to find additional, less toxic treatments in the near future. |
| Databáze: | OpenAIRE |
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