Amyotrophic Lateral Sclerosis (ALS)Phase 2NCT00231140
Pilot-Study of Thalidomide in Amyotrophic Lateral Sclerosis (ALS)
A Phase 2 study testing Thalidomide (drug) in people with Amyotrophic Lateral Sclerosis (ALS), run by Charite University, Berlin, Germany at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 25 to 80 years
- Conditions the study is for
- Amyotrophic Lateral Sclerosis (ALS)
- What is being tested?
- Thalidomide (drug)
- How many people
- 40 participants
- Where
- 1 siteGermany
- Study dates
- Dec 2005to Aug 2006
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
Show all 15Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
Germany1 site
Charite University Hospital, Berlin, Germany
Berlin, State of Berlin, 13353
About this 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)
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.
Read the 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)
- Being tested
- Thalidomide (drug)
- Keywords
- ALS, motor neuron disease
- Medical subject headings
- Amyotrophic Lateral Sclerosis, Motor Neuron Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Thalidomide (drug)Drug
What is being measured
The primary outcome is the main question the study is designed to answer.
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
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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2005 (estimated)
- Study startDec 2005
- Study completionAug 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Amyotrophic Lateral Sclerosis (ALS)Studies of the same condition, open and under way.
- More trials run by Charite University, Berlin, GermanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants
Sponsor and investigators
- Lead sponsor
- Charite University, Berlin, Germany
- Sponsor type
- University, hospital or other
- Investigators
- Thomas Meyer, MD, Study chair, Charité University Hospital, Berlin, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00231140
- Sponsor's protocol ID
- THL-ALS01
- Status last verified
- Jan 2007
- First submitted
- 30 Sep 2005
- Last updated
- 19 Jan 2007
- Results posted
- No
Publications
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.
PubMed 18425621
Study at a glance
From the registry record, last updated by the sponsor on 19 Jan 2007. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT00231140
- Acronym / sponsor ID
- THL-ALS01
- Conditions
- Amyotrophic Lateral Sclerosis (ALS)
- Keywords
- ALS, motor neuron disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 40 participants
- Lead sponsor
- Charite University, Berlin, GermanyUniversity, hospital or other
- Study start
- Dec 2005
- Study completion
- Aug 2006
- First posted
- 4 Oct 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
Who may qualify
- Ages
- 25 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Thalidomide (drug) | Drug | – |
Primary outcome
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
8 secondary outcomes
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
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jan 2007.
- Derived from this study: PubMed 18425621Meyer 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.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thomas Meyer, MD study chair
Charité University Hospital, Berlin, Germany
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Thalidomide (drug) in people with Amyotrophic Lateral Sclerosis (ALS), run by Charite University, Berlin, Germany at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Jan 2007. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
to evaluate the long-term safety and tolerability of thalidomide. The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00231140, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jan 2007.