NCT06177028

MCLENA-2: A Phase II Clinical Trial for the Assessment of Lenalidomide in Patients With Mild Cognitive Impairment

MCLENA-2: A Phase II Clinical Trial for the Assessment of Biomarker Trajectory in Patients With Mild Cognitive Impairment Due to Alzheimer's Disease Treated With Lenalidomide (Amendment to IND # 142121)

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 45 (estimated)
• Sponsor: St. Joseph's Hospital and Medical Center, Phoenix · Academic / Other
• Sex: All
• Age: 50 Years – 90 Years
• Healthy volunteers: Accepted

Summary

This is a randomized, double-blind, placebo-controlled, parallel group study. The use of placebo is appropriate to minimize bias related to treatment expectations of the subject, study partner, and site investigator, as well as to changes in the relationship between the subject and study partner that might occur with the initiation of treatment and expectation of improvement in motor symptoms or cognition. Changes in subject/study partner interactions can impact subject mood and might introduce biases that cannot be quantified. The double-blind use of placebo will also prevent bias in the clinical and scientific assessments.

Detailed description

There are currently no FDA-approved medications indicated for the treatment 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 we aim to test the central hypothesis that lenalidomide reduces inflammatory and AD-associated pathological biomarkers in the blood and CSF. For this, we designed a 6-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 continuously for 26 weeks and 4 weeks washout (total of 30 weeks).

Conditions

• Cognitive Impairment, Mild
• Cognitive Dysfunction
• Amyloid Plaque
• Neurodegenerative Disease, Hereditary
• Inflammation, Brain

Interventions

Type	Name	Description
DRUG	Lenalidomide 10 mg	Lenalidomide is a cancer drug, It is also known by it's brand name Revlimid.

Timeline

• Start date: 2025-06-01
• Primary completion: 2026-01-02
• Completion: 2027-01-02
• First posted: 2023-12-20
• Last updated: 2025-05-18

Regulatory

• FDA-regulated drug study