Pilot-Study of Thalidomide in Amyotrophic Lateral Sclerosis (ALS)
Status:
Terminated
Trial end date:
2006-08-01
Target enrollment:
Participant gender:
Summary
Neuroinflammation has recently emerged as a significant contributor to motor neuron damage.
ALS tissue is characterized by inflammatory changes that are observed in both sporadic and
familial ALS and in the ALS superoxide dismutase 1 (SOD1) transgenic mouse model. They
include an accumulation of large numbers of activated microglia and astrocytes.
Proinflammatory cytokines, such as tumor necrosis factor (TNF-), are robustly upregulated in
ALS. The receptor for tumor necrosis factor- (TNF-R1) is elevated at late presymptomatic as
well as symptomatic phases of disease. TNF acts as a principal driver for neuroinflammation
in ALS, while several co-stimulating cytokines and chemokines act to potentiate the TNF
effects [4-6].
We propose an investigational therapy of ALS with oral administration of thalidomide. The
rationale for this study is based on the anti-inflammatory properties of thalidomide through
the modulation of inflammatory cytokines such as TNF. The primary aim of the trial is to
determine whether treatment with thalidomide is safe and well tolerated in conjunction with
riluzole and whether patients with ALS can tolerate daily doses of up to 400 mg. The trial is
designed as feasibility study in planning for a larger phase IIb/III trial of efficacy.