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

NCT00231140 | Terminated Phase 2

• 1 other identifier: THL-ALS01
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Amyotrophic Lateral Sclerosis (ALS)

Keywords

ALS, motor neuron disease

Outcome Measures

Primary Outcomes (2)

• to evaluate the long-term safety and tolerability of thalidomide

• to compare the total number of adverse events (AE), abnormal laboratory tests, and number of patients who completed the study between groups

Secondary Outcomes (8)

• to evaluate the clinical effect of two oral doses of the thalidomide on the rate of functional decline in ALS patients measured by the ALS Functional Rating Scale-revised (ALS-FRS-R) over a 24 week treatment period

• to investigate the effects of thalidomide on pulmonary function (forced vital capacity) over a 24 week treatment period

• to evaluate the sleep quality and somnolence using the Epworth Sleeping Scale: ESS ≥ 18

• to evaluate the frequency and severity of sensory neuropathy using the inflammatory neuropathy cause and treatment sensory sum score - ISS ≥ 4

• to evaluate the frequency of thrombotic events

Interventions

Thalidomide (drug) DRUG

Eligibility Criteria

• Age: 25 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patients aged 25 and 80 years
• female patients who are either postmenopausal for at least 24 month or who are willing and able to practice the methods of contraception following the Pharmion-Risk Managment Program (PRMP)
• Male patients who are willing and able to practice the methods of contraception along with their female partners of childbearing potential following the PRMP
• Clinical diagnosis of probable and definite ALS
• Sporadic or familial ALS
• Onset of pareses for no more than 4 years
• Vital capacity equal to or more than 65% of the predicted value
• Treatment with riluzole 100mg/day
• Patients who are willing to give informed consent

You may not qualify if:

• pregnancy or breast feeding
• female patients who are unwilling or unable to practice the methods of contraception following the Pharmion-Risk Managment Program (PRMP)
• Male patients who are willing and able to practice the methods of contraception along with their female partners of childbearing potential following the PRMP
• Patients unlikely to comply with the PRMP and other study requirements
• Patients with significant sensory abnormalities, dementia, uncompensated medical illnesses and psychiatric disorders
• Laboratory abnormalities consistent with clinically significant cardiovascular, respiratory, haematological, metabolic, hepatic and renal disease
• Infectious disease including HIV, hepatitis B and C
• monoclonal gammopathy of unknown significance (MGUS)
• History of substance abuse within the past year
• History of recurrent thrombosis
• Continuous non-invasive ventilation (ventilation-free interval equal to or less than 2 hours daily)
• Tracheotomy and invasive ventilation
• Treatment with investigational drug within 3 months prior to screening
• patients with clinically signifikant sensory polyneuropathy (inflammatory neuropathy cause and treatment sensory sum score - ISS ≥ 2)
• patients with sleep disorder (Epworth Sleeping Scale-ESS ≥ 10)

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead

Study Sites (1)

Charite University Hospital, Berlin, Germany

Berlin, State of Berlin, 13353, Germany

Location

Related Publications (1)

• Meyer T, Maier A, Borisow N, Dullinger JS, Splettstosser G, Ohlraun S, Munch C, Linke P. Thalidomide causes sinus bradycardia in ALS. J Neurol. 2008 Apr;255(4):587-91. doi: 10.1007/s00415-008-0756-3. Epub 2008 Apr 21.

  PMID: 18425621 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Motor Neuron Disease

Interventions

Thalidomide; Pharmaceutical Preparations

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Thomas Meyer, MD

  Charité University Hospital, Berlin, Germany

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 30, 2005
• First Posted: October 4, 2005
• Study Start: December 1, 2005
• Study Completion: August 1, 2006
• Last Updated: January 19, 2007

Record last verified: 2007-01

Locations

DE (1)