Oxidative Stress in Motor Neuron Disease: COSMOS Add-On Study
| Status: | Completed |
|---|---|
| Conditions: | Neurology, Psychiatric |
| Therapuetic Areas: | Neurology, Psychiatry / Psychology |
| Healthy: | No |
| Age Range: | 20 - Any |
| Updated: | 2/28/2019 |
| Start Date: | May 13, 2010 |
| End Date: | August 3, 2015 |
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.
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.
- 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.
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.
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.
- INCLUSION CRITERIA:
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
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
EXCLUSION CRITERIA:
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
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
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