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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00231140
Recruitment Status : Terminated
First Posted : October 4, 2005
Last Update Posted : January 19, 2007
Information provided by:
Charite University, Berlin, Germany

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.

Condition or disease Intervention/treatment Phase
Amyotrophic Lateral Sclerosis (ALS) Drug: Thalidomide (drug) Phase 2

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).

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Study Type : Interventional  (Clinical Trial)
Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Study Start Date : December 2005
Study Completion Date : August 2006

Primary Outcome Measures :
  1. to evaluate the long-term safety and tolerability of thalidomide
  2. to compare the total number of adverse events (AE), abnormal laboratory tests, and number of patients who completed the study between groups

Secondary Outcome Measures :
  1. 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
  2. to investigate the effects of thalidomide on pulmonary function (forced vital capacity) over a 24 week treatment period
  3. to evaluate the sleep quality and somnolence using the Epworth Sleeping Scale: ESS ≥ 18
  4. to evaluate the frequency and severity of sensory neuropathy using the inflammatory neuropathy cause and treatment sensory sum score - ISS ≥ 4
  5. to evaluate the frequency of thrombotic events
  6. to determine the number of patients who require continuous non-invasive ventilation or invasive ventilation
  7. to determine the number of patients who require percutanous endoscopic gastrostomy (PEG)
  8. to evaluate the survival time or the time point until invasive ventilation is started

Information from the National Library of Medicine

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Ages Eligible for Study:   25 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00231140

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Charite University Hospital, Berlin, Germany
Berlin, Germany, 13353
Sponsors and Collaborators
Charite University, Berlin, Germany
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Study Chair: Thomas Meyer, MD Charité University Hospital, Berlin, Germany
Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information Identifier: NCT00231140    
Other Study ID Numbers: THL-ALS01
First Posted: October 4, 2005    Key Record Dates
Last Update Posted: January 19, 2007
Last Verified: January 2007
Keywords provided by Charite University, Berlin, Germany:
ALS, motor neuron disease
Additional relevant MeSH terms:
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Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents