NCT04032626

MCLENA-1: A Clinical Trial for the Assessment of Lenalidomide in Amnestic MCI Patients

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

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 15 (actual)
• Sponsor: St. Joseph's Hospital and Medical Center, Phoenix · Academic / Other
• Sex: All
• Age: 50 Years – 89 Years
• Healthy volunteers: Not accepted

Summary

Accumulating evidence indicates that inflammation is prominent both in the blood and central nervous system (CNS) of Alzheimer's disease (AD) patients. These data suggest that systemic inflammation plays a crucial role in the cause and effects of AD neuropathology. Capitalizing on the experience from a previous clinical trial with thalidomide, here, the investigators hypothesize that modulating both systemic and CNS inflammation via the pleiotropic immunomodulator lenalidomide is a putative therapeutic intervention for AD if administered at a proper time window during the course of the disease.

Detailed description

There are currently no approved treatments to treat the neuroinflammatory aspects of AD. While inflammation is pervasive to many neurological disorders, no clinical trial has yet demonstrated the efficacy of anti-inflammatory agents for AD. Interestingly, chronic peripheral low-grade inflammation is associated with aging and increases the risk for disease and mortality, including AD. Accumulating evidence indicates that nuclear factor-kappa B, tumor necrosis factor alpha (TNFα), interleukins (e.g. IL-1beta, IL-2, and IL-6), and chemokines (e.g. IL-8) are found elevated both in the blood and central nervous system (CNS) of AD patients. These data confirm that inflammation plays a central role in the cause and effect of AD neuropathology. The immunomodulator, anti-cancer agent lenalidomide is one of the very few pleiotropic agents 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. In the current project the investigators aim to test the central hypothesis that lenalidomide reduces inflammatory and AD-associated pathological biomarkers, and improves cognition. For this, the investigators designed an 18-month, Phase II, double-blind, randomized, two-armed, parallel group, placebo controlled, and proof-of-mechanism clinical study in early symptomatic AD subjects (i.e. amnestic mild cognitive impairment; aMCI). The effects of lenalidomide treatment will be assessed after 12 months of treatment and 6 months washout (month 18).

Conditions

• Cognitive Impairment, Mild
• Cognitive Dysfunction
• Amyloid Plaque
• Neurodegeneration
• Inflammation, Brain

Interventions

Type	Name	Description
DRUG	Lenalidomide 10 mg	Lenalid
DRUG	Placebo	Placebo

Timeline

• Start date: 2020-07-22
• Primary completion: 2025-05-31
• Completion: 2025-05-31
• First posted: 2019-07-25
• Last updated: 2025-06-13

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study