Motor Neuron DiseaseNCT01143428
Oxidative Stress in Motor Neuron Disease: COSMOS Add-On Study
An observational study of Motor Neuron Disease and Primary Lateral Sclerosis, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
Background: Primary lateral sclerosis (PLS) is a disorder in which nerve cells in the brain that control movement degenerate. The cause of PLS is not known, but some research has suggested that environmental factors that produce oxidative stress trigger PLS in people who carry certain genes. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Motor Neuron Disease, Primary Lateral Sclerosis
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 13 May 2010to 3 Aug 2015
- Phase
- Observational
- 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 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients will be included if they:
- Are 20 years or older
- Have PLS, that is pure UMN dysfunction (spasticity, pathological hyperreflexia, pathological reflexes with or without motor weakness) of undetermined etiology
- Have been evaluated at NIH and are being willing to return for active follow-up for 3 years
- Had PLS symptom onset at least 5 years prior to the study enrollment but not more than 15 years
- Have normal nerve conduction studies and normal needle electrode examination performed within 12 months of the time of enrollment in this study
Show all 10Show fewer
- Have no other definable diseases causing spasticity such as structural brain or spinal cord disease, metabolic diseases, paraneoplastic syndromes, hereditary diseases, infectious diseases, or other significant neurological abnormalities
- Have a reliable family caregiver who can assist in providing responses on telephone interviews and questionnaires if the proband has problems with speaking or writing
- Are fluent in English
- Ability to provide his/her own informed consent
Who cannot join
- Patients will be excluded if they:
- Have EMG evidence of active denervation or fasciculations in more than a few muscles with chronic neurogenic motor unit potentials at the time of enrollment
- Have only lower extremity involvement
- Have major medical diseases (e.g. active cancer, dialysis) that have required active medical treatment within the past 6 months
- Are participating in clinical treatment trials at the time of enrollment and acquisition of baseline biological samples (participation in clinical trials after the baseline visit is permitted)
- Are unwilling or unable to return for follow-up visits
- Have pacemakers or other implanted electrical devices, which might make TMS unsafe will be excluded from TMS testing
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Oxidative Stress in Motor Neuron Disease: COSMOS-PLS Add-On Study
Background:
- Primary lateral sclerosis (PLS) is a disorder in which nerve cells in the brain that control movement degenerate. The cause of PLS is not known, but some research has suggested that environmental factors that produce oxidative stress trigger PLS in people who carry certain genes. Oxidative stress is caused when the body makes chemicals called "free radicals" faster than its natural systems can break them down. Oxidative stress can be triggered by exposures to chemicals related to the bodily effects of lead, smoking, alcohol consumption, physical activity, and psychological stress. Chemicals produced by the body during oxidative stress can be measured in the blood and urine. Researchers are interested in studying the physical, neurological, and chemical effects of PLS to better understand the effects of oxidative stress on the disorder.
Read more
Objectives:
- To study the relation of oxidative stress to the diagnosis and progression of motor neuron disease.
Eligibility:
- Individuals 20 years of age or older who have been diagnosed with PLS, and have had symptoms of PLS for at least 5 but not more than 8 years and been previously enrolled in 01-N-0145 Screening: Neurologic Disorders with Muscle Stiffness
Design:
- Participants will have an initial study visit and three follow-up visits. Each visit will require approximately 3 days of testing at the National Institutes of Health Clinical Center.
- As part of this study, participants will have the following tests and procedures:
- Neurological examination to test muscle strength, sensation, coordination, and reflexes, as well as clarity of speech
- Tests of memory, attention, concentration, and thinking
- Surveys on oxidative stress, including questions on life, mood, jobs held, and habit
- Electromyography to record the electrical activity of muscles
- Transcranial magnetic stimulation to measure electrical activity translated from their brain to the muscles
- Blood, urine, and skin biopsy samples for testing and sample collection
- After the initial visit, participants will have three more visits, once each in the following 3 years.
Read the detailed description
Objective
Primary lateral sclerosis (PLS) and amyotrophic lateral sclerosis (ALS) are motor neuron disorders with different phenotypes that progress at very different rates. ALS is a rapidly progressive disease with a median survival less than 5 years. Patients with PLS have a slowly progressive course with a normal lifespan. One hypothesis is that oxidative stress affects the way in which different motor neuron disorders progress. To test this hypothesis, exposures to putative triggers of oxidative stress and biomarkers that may reflect oxidative stress will be assessed in patients with motor neuron disorders. A multicenter effort (the COSMOS study) has been initiated to accumulate sufficient numbers of ALS patients to address this hypothesis. As an add-on study, PLS patients will also be assessed in the multicenter effort. The objective of this protocol is to enroll PLS patients in this multicenter effort. The goal is to assess environmental factors and markers of oxidative stress in patients with established PLS.
Study Population
15 adult patients with PLS who have symptoms of pure upper motor neuron dysfunction for at least 5 but not more than 15 years.
Design
Patients will undergo a standard battery of clinical, physiological, and cognitive screening tests at enrollment, with scheduled follow-up evaluation visits every 12 months for 36 months. Blood and urine samples will be sent to collaborators at Columbia University for analysis of markers of oxidative injury and genetic risk factors. Patients will complete a self-administered nutritional survey and will be interviewed by phone by Columbia University investigators using questionnaires to assess environmental, occupational, lifestyle and psychosocial factors thought to be triggers of oxidative stress.
Outcome Measures
The Columbia University collaborators will combine data from several centers in a regression model correlating the slope of decline of the ALS-FRS score with an index of oxidative stress.
- Conditions
- Motor Neuron Disease, Primary Lateral Sclerosis
- Keywords
- Motor Neuron Disease, Primary Lateral Sclerosis, Oxidative Stress, Physiology, PLS
- Medical subject headings
- Motor Neuron Disease
What is being measured
The primary outcome is the main question the study is designed to answer.
Decline in ALSFRS score
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2010 (estimated)
- Study start13 May 2010
- Study completion3 Aug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Motor Neuron DiseaseStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The 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
- Observational
- Time perspective
- Other
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Mary Kay Floeter, M.D., Principal investigator, National Institute of Neurological Disorders and Stroke (NINDS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01143428
- Sponsor's protocol ID
- 100121
- Other IDs
- 10-N-0121
- Status last verified
- 3 Aug 2015
- First submitted
- 11 Jun 2010
- Last updated
- 5 Nov 2019
- Results posted
- No
Publications
Gordon PH, Cheng B, Katz IB, Mitsumoto H, Rowland LP. Clinical features that distinguish PLS, upper motor neuron-dominant ALS, and typical ALS. Neurology. 2009 Jun 2;72(22):1948-52. doi: 10.1212/WNL.0b013e3181a8269b.
PubMed 19487653Strong MJ, Gordon PH. Primary lateral sclerosis, hereditary spastic paraplegia and amyotrophic lateral sclerosis: discrete entities or spectrum? Amyotroph Lateral Scler Other Motor Neuron Disord. 2005 Mar;6(1):8-16. doi: 10.1080/14660820410021267.
PubMed 16036421Tartaglia MC, Rowe A, Findlater K, Orange JB, Grace G, Strong MJ. Differentiation between primary lateral sclerosis and amyotrophic lateral sclerosis: examination of symptoms and signs at disease onset and during follow-up. Arch Neurol. 2007 Feb;64(2):232-6. doi: 10.1001/archneur.64.2.232.
PubMed 17296839
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Oxidative Stress in Motor Neuron Disease: COSMOS-PLS Add-On Study
- ClinicalTrials.gov ID
- NCT01143428
- Acronym / sponsor ID
- 100121
- Conditions
- Motor Neuron Disease, Primary Lateral Sclerosis
- Keywords
- Motor Neuron Disease, Primary Lateral Sclerosis, Oxidative Stress, Physiology, PLS
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 13 May 2010
- Study completion
- 3 Aug 2015
- First posted
- 14 Jun 2010 (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.
Background:
- Primary lateral sclerosis (PLS) is a disorder in which nerve cells in the brain that control movement degenerate. The cause of PLS is not known, but some research has suggested that environmental factors that produce oxidative stress trigger PLS in people who carry certain genes. Oxidative stress is caused when the body makes chemicals called "free radicals" faster than its natural systems can break them down. Oxidative stress can be triggered by exposures to chemicals related to the bodily effects of lead, smoking, alcohol consumption, physical activity, and psychological stress. Chemicals produced by the body during oxidative stress can be measured in the blood and urine. Researchers are interested in studying the physical, neurological, and chemical effects of PLS to better understand the effects of oxidative stress on the disorder.
Objectives:
- To study the relation of oxidative stress to the diagnosis and progression of motor neuron disease.
Eligibility:
- Individuals 20 years of age or older who have been diagnosed with PLS, and have had symptoms of PLS for at least 5 but not more than 8 years and been previously enrolled in 01-N-0145 Screening: Neurologic Disorders with Muscle Stiffness
Design:
- Participants will have an initial study visit and three follow-up visits. Each visit will require approximately 3 days of testing at the National Institutes of Health Clinical Center.
- As part of this study, participants will have the following tests and procedures:
- Neurological examination to test muscle strength, sensation, coordination, and reflexes, as well as clarity of speech
- Tests of memory, attention, concentration, and thinking
- Surveys on oxidative stress, including questions on life, mood, jobs held, and habit
- Electromyography to record the electrical activity of muscles
- Transcranial magnetic stimulation to measure electrical activity translated from their brain to the muscles
- Blood, urine, and skin biopsy samples for testing and sample collection
- After the initial visit, participants will have three more visits, once each in the following 3 years.
Detailed description
Objective
Primary lateral sclerosis (PLS) and amyotrophic lateral sclerosis (ALS) are motor neuron disorders with different phenotypes that progress at very different rates. ALS is a rapidly progressive disease with a median survival less than 5 years. Patients with PLS have a slowly progressive course with a normal lifespan. One hypothesis is that oxidative stress affects the way in which different motor neuron disorders progress. To test this hypothesis, exposures to putative triggers of oxidative stress and biomarkers that may reflect oxidative stress will be assessed in patients with motor neuron disorders. A multicenter effort (the COSMOS study) has been initiated to accumulate sufficient numbers of ALS patients to address this hypothesis. As an add-on study, PLS patients will also be assessed in the multicenter effort. The objective of this protocol is to enroll PLS patients in this multicenter effort. The goal is to assess environmental factors and markers of oxidative stress in patients with established PLS.
Study Population
15 adult patients with PLS who have symptoms of pure upper motor neuron dysfunction for at least 5 but not more than 15 years.
Design
Patients will undergo a standard battery of clinical, physiological, and cognitive screening tests at enrollment, with scheduled follow-up evaluation visits every 12 months for 36 months. Blood and urine samples will be sent to collaborators at Columbia University for analysis of markers of oxidative injury and genetic risk factors. Patients will complete a self-administered nutritional survey and will be interviewed by phone by Columbia University investigators using questionnaires to assess environmental, occupational, lifestyle and psychosocial factors thought to be triggers of oxidative stress.
Outcome Measures
The Columbia University collaborators will combine data from several centers in a regression model correlating the slope of decline of the ALS-FRS score with an index of oxidative stress.
Study design
- Time perspective
- Other
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Are 20 years or older
- Have PLS, that is pure UMN dysfunction (spasticity, pathological hyperreflexia, pathological reflexes with or without motor weakness) of undetermined etiology
- Have been evaluated at NIH and are being willing to return for active follow-up for 3 years
- Had PLS symptom onset at least 5 years prior to the study enrollment but not more than 15 years
- Have normal nerve conduction studies and normal needle electrode examination performed within 12 months of the time of enrollment in this study
Key exclusion criteria (7 listed)
- Have EMG evidence of active denervation or fasciculations in more than a few muscles with chronic neurogenic motor unit potentials at the time of enrollment
- Have only lower extremity involvement
- Have major medical diseases (e.g. active cancer, dialysis) that have required active medical treatment within the past 6 months
- Are participating in clinical treatment trials at the time of enrollment and acquisition of baseline biological samples (participation in clinical trials after the baseline visit is permitted)
- Are unwilling or unable to return for follow-up visits
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Decline in ALSFRS score
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2019.
- Background: PubMed 19487653Gordon PH, Cheng B, Katz IB, Mitsumoto H, Rowland LP. Clinical features that distinguish PLS, upper motor neuron-dominant ALS, and typical ALS. Neurology. 2009 Jun 2;72(22):1948-52. doi: 10.1212/WNL.0b013e3181a8269b.
- Background: PubMed 16036421Strong MJ, Gordon PH. Primary lateral sclerosis, hereditary spastic paraplegia and amyotrophic lateral sclerosis: discrete entities or spectrum? Amyotroph Lateral Scler Other Motor Neuron Disord. 2005 Mar;6(1):8-16. doi: 10.1080/14660820410021267.
- Background: PubMed 17296839Tartaglia MC, Rowe A, Findlater K, Orange JB, Grace G, Strong MJ. Differentiation between primary lateral sclerosis and amyotrophic lateral sclerosis: examination of symptoms and signs at disease onset and during follow-up. Arch Neurol. 2007 Feb;64(2):232-6. doi: 10.1001/archneur.64.2.232.
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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.
Mary Kay Floeter, M.D. principal investigator
National Institute of Neurological Disorders and Stroke (NINDS)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Motor Neuron Disease and Primary Lateral Sclerosis, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
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 10 inclusion and 7 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: finished, as of the sponsor's last update on 5 Nov 2019. 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 United States. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Decline in ALSFRS score. 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 NCT01143428, which also lists 3 linked publications.
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 5 Nov 2019.