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

January 18, 2007 updated by: Charite University, Berlin, Germany

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)

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment

40

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Berlin, Germany, 13353
        • Charité University Hospital, Berlin, Germany

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

25 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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

Outcome Measure
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Charite University, Berlin, Germany

Investigators

  • Study Chair: Thomas Meyer, MD, Charité University Hospital, Berlin, Germany

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2005

Study Completion

August 1, 2006

Study Registration Dates

First Submitted

September 30, 2005

First Submitted That Met QC Criteria

September 30, 2005

First Posted (Estimate)

October 4, 2005

Study Record Updates

Last Update Posted (Estimate)

January 19, 2007

Last Update Submitted That Met QC Criteria

January 18, 2007

Last Verified

January 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • THL-ALS01

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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