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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

Authors Decourt B, Wilson J, Ritter A, Dardis C, DiFilippo FP, Zhuang X, Cordes D, Lee G, Fulkerson ND, St Rose T, Hartley K, Sabbagh MN

Received 4 July 2019

Accepted for publication 9 October 2019

Published 7 January 2020 Volume 2020:12 Pages 1—13


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Professor Arthur Frankel

Boris Decourt,1 Jeffrey Wilson,2 Aaron Ritter,1 Christopher Dardis,3 Frank P DiFilippo,4 Xiaowei Zhuang,1 Dietmar Cordes,1 Garam Lee,1 Nadia D Fulkerson,1 Tessa St Rose,1 Katurah Hartley,1 Marwan N Sabbagh1

1Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA; 2Department of Economics W. P. Carey School of Business, Arizona State University, Tempe, AZ, USA; 3Barrow Neurological Institute, Phoenix, AZ, USA; 4Cleveland Clinic Department of Nuclear Medicine, Cleveland, OH, USA

Correspondence: Marwan N Sabbagh
Cleveland Clinic Lou Ruvo Center for Brain Health, 888 W.Bonneville Avenue, Las Vegas 89106, NV, USA
Tel +1-702-483-6029
Fax +1-702-722-6584

Abstract: 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.

Keywords: Alzheimer’s disease, biomarkers, brain amyloid, brain imaging, clinical trial, cognition, cytokines, dementia, hematologic changes, immunomodulation, inflammation, lenalidomide

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