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

Sponsored by:	Charite University, Berlin, Germany
Information provided by:	Charite University, Berlin, Germany
ClinicalTrials.gov Identifier:	NCT00231140

Purpose

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	Intervention	Phase
Amyotrophic Lateral Sclerosis (ALS)	Drug: Thalidomide (drug)	Phase II

Genetics Home Reference related topics: amyotrophic lateral sclerosis

MedlinePlus related topics: Amyotrophic Lateral Sclerosis

Drug Information available for: Thalidomide Riluzole

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Dose Comparison, Parallel Assignment, Safety/Efficacy Study
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)

Further study details as provided by Charite University, Berlin, Germany:

Primary Outcome Measures:

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 Outcome Measures:

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
to determine the number of patients who require continuous non-invasive ventilation or invasive ventilation
to determine the number of patients who require percutanous endoscopic gastrostomy (PEG)
to evaluate the survival time or the time point until invasive ventilation is started

Estimated Enrollment:	40
Study Start Date:	December 2005
Estimated Study Completion Date:	August 2006

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).

Eligibility

Ages Eligible for Study:	25 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00231140

Locations

Germany
Charite University Hospital, Berlin, Germany
Berlin, Germany, 13353

Sponsors and Collaborators

Charite University, Berlin, Germany

Investigators

Study Chair:

Thomas Meyer, MD

Charité University Hospital, Berlin, Germany

More Information

Related Info This link exits the ClinicalTrials.gov site

Study ID Numbers:	THL-ALS01
Study First Received:	September 30, 2005
Last Updated:	January 18, 2007
ClinicalTrials.gov Identifier:	NCT00231140
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Charite University, Berlin, Germany:

ALS, motor neuron disease

Study placed in the following topic categories:

Riluzole
Spinal Cord Diseases
Thalidomide
Central Nervous System Diseases
Sclerosis
Degenerative motor system disease
Neurodegenerative Diseases

Motor neuron disease
Amyotrophic lateral sclerosis
Neuromuscular Diseases
Amyotrophic Lateral Sclerosis
Lou Gehrig's disease
Motor Neuron Disease

Additional relevant MeSH terms:

Anti-Infective Agents
Immunologic Factors
Antineoplastic Agents
Growth Substances
Nervous System Diseases
Physiological Effects of Drugs
Immunosuppressive Agents
Angiogenesis Inhibitors

Pharmacologic Actions
Anti-Bacterial Agents
Pathologic Processes
Therapeutic Uses
Growth Inhibitors
Angiogenesis Modulating Agents
Leprostatic Agents

ClinicalTrials.gov processed this record on January 14, 2009