NCT00231140

Pilot-Study of Thalidomide in Amyotrophic Lateral Sclerosis (ALS)

Randomized, Open, Parallel Group Study for the Evaluation of an Oral Dose of 100 mg Thalidomide and Subsequent Dose Escalation of 400 mg Thalidomide in Combination With Riluzole in Patients With Amyotrophic Lateral Sclerosis (ALS)

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (planned)
• Sponsor: Charite University, Berlin, Germany · Academic / Other
• Sex: All
• Age: 25 Years – 80 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Study drug will be provided as 50 mg tablets. Patients will be instructed to take 2 tablets orally once a day during the evening at least 60 minutes after a meal. Thalidomide will be administered starting at 100 mg (Group 1) for 6 weeks. Thereafter, the dose will be increased every week by 50mg until reaching the dose of 400 mg/day. This treatment is continued for 12 weeks. Thalidomide is administered in conjunction with the standard treatment of riluzole (100mg/day).

Conditions

• Amyotrophic Lateral Sclerosis (ALS)

Interventions

Type	Name	Description
DRUG	Thalidomide (drug)

Timeline

• Start date: 2005-12-01
• Completion: 2006-08-01
• First posted: 2005-10-04
• Last updated: 2007-01-19

Locations

1 site across 1 country: Germany