Amyotrophic Lateral Sclerosis, FamilialNCT03449212
SOD1 Kinetics Measurements in ALS Patients
An observational study of Amyotrophic Lateral Sclerosis, Familial and Amyotrophic Lateral Sclerosis, Sporadic, run by Washington University School of Medicine at 1 site in United States.
Trial summary
Washington University in St. Louis is seeking participants with ALS for a study to determine the half-life of the protein SOD1 in the cerebral spinal fluid. Mutations in the SOD1 gene are known to cause some forms of familial ALS. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Amyotrophic Lateral Sclerosis, Familial, Amyotrophic Lateral Sclerosis, Sporadic
- How many people
- 86 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2012to Dec 2026
- 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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Known SOD1 positive ALS status, sporadic ALS and SOD1 positive carriers (non-ALS).
Who may be able to join
- Males or females of any race aged 18 or older
- Positive for SOD1 mutation (SOD1 ALS only)
- Diagnosed with Definite, Probable or Possible ALS in accordance with El Escorial criteria (ALS and SOD1 Positive ALS only)
- Able to hold position and breathe comfortably for the duration of the LP procedure as determined by the LP physician or Nurse Practitioner
- Subjects must be able to provide informed consent
Who cannot join
- Invasive ventilator dependence, such as tracheostomy
- Medically unable to undergo lumbar puncture (LP) as determined by the investigator (i.e.,bleeding disorder, allergy to local anesthetics, a skin infection at or near the LP site, or evidence of high intracranial pressure).
- Any active dermatologic disease.
- Any connective tissue disease including systemic lupus erythematous, Sjögren's syndrome, scleroderma or mixed connective tissue disease.
- Any known or suspected abnormal CSF pressure or intracranial/intraspinal tumors.
- Use of anticoagulant medication (eg. warfarin, dalteparin, enoxaparin, rivaroxaban, fondaparinux, dabigatran) that cannot be safely withheld until coagulation parameters have normalized prior to lumbar puncture and for up to a week following the lumbar puncture.
Show all 12Show fewer
- Blood dyscrasia, abnormal bleeding diathesis, or the use of dialysis for renal failure.
- Clinical judgment of the Site Investigator that the subject would be unable to undergo multiple lumbar punctures.
- Safety lab values greater than 2X the upper limit of normal
- Allergy to Lidocaine
- Pregnancy
- Any contraindication for lumbar puncture
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University in St. Louis
St Louis, Missouri, 63110
About this study
Washington University in St. Louis is seeking participants with ALS for a study to determine the half-life of the protein SOD1 in the cerebral spinal fluid. Mutations in the SOD1 gene are known to cause some forms of familial ALS. Researchers are developing a treatment to reduce the level of SOD1 in familial ALS, but need to know more about how long SOD1 stays in the body ("half-life") to help determine if the new treatment is effective.
Read the detailed description
Background: Novel targeted therapeutic strategies are being developed for genetic subsets of ALS, such as those caused by dominantly inherited mutations in the superoxide dismutase 1 gene (SOD1). Investigators have developed an antisense oligonucleotide (ASO) inhibitor of SOD1 biosynthesis for ALS patients who carry mutations in SOD1. This ASO is now ready for clinical trial (ClinicalTrials.gov #NCT02623699). The initial success of the ASO will depend on showing a pharmacodynamics result on SOD1 in participants, and thus a key challenge in applying this targeted therapy involves rigorous examination of pharmacodynamics markers.
The Investigator's previous data suggest that SOD1 in the cerebral spinal fluid (CSF) will be an excellent pharmacodynamics marker for an SOD1-focused therapeutic approach. However, one of the central missing components in understanding SOD1 as a marker is SOD1 CSF half-life data. The half-life of this protein will aid in clinical trial planning since half-life influences the amount of SOD1 protein reduction by ASO and thus dictates the optimal timing of drug administration and CSF collection for pharmacodynamics measures.
Objectives:
- Enroll a total of 86 ALS participants
- Determine the kinetics for total SOD1 protein, as well as the wild type and mutant protein separately
- Determine this in patients with known SOD1 mutation as well as sporadic ALS patients Eligibility
- Adults over age 18
- fALS with confirmed genetic testing showing a mutation in the SOD1 gene; asymptomatic SOD1 gene carriers and sporadic ALS patients.
Measures: The key outcome of this study is to determine the half-life of the SOD1 protein in symptomatic and asymptomatic ALS patients which will provide critical information to inform future therapeutic studies in ALS. For ALS patients, The Investigators will also perform Slow Vital Capacity testing and the ALSFRS-R at the screening visit and at each lumbar puncture visit.
Measures: Participants will have up to 7 in-person visits over 4 months. The study involves labeling or marking SOD1 with a special type of leucine. Leucine is an essential amino acid that is found in the foods we eat. This method involves an overnight stay for a 16 hour intravenous infusion of labeled leucine along with a collection blood and urine followed by 5 lumbar punctures scheduled over the period of 4 months.
At each subsequent visit, subjects will undergo a blood draw, urine collection, lumbar puncture, a questionnaire (ALS Functional Rating Scale) which measures motor function, and a breathing test to determine Slow Vital Capacity (SVC) measurements.
Analysis: In addition to determining the half-life of the SOD1 protein in ALS patients, the Investigators will also analyze the kinetics of wild type SOD1 protein separately from mutant SOD1 protein to determine differences in half life. The Investigators will also compare CSF Tau half-life between ALS patients and controls as a disease specificity control. The Investigators hope to correlate this data with clinical measures which may reveal other important hypotheses regarding SOD1 kinetic rates and disease manifestations.
- Keywords
- SOD1, Amyotrophic Lateral Sclerosis, ALS, Kinetics, Amyotrophic Lateral Sclerosis, Familial, Amyotrophic Lateral Sclerosis, Sporadic
- Medical subject headings
- Amyotrophic lateral sclerosis 1, Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| SOD1 ALS | Not described | |
| Sporadic ALS | Not described | |
| Asymptomatic SOD1 gene carriers | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary outcome measurement will be the determination of the SOD1 half-life in the CSF of each subject.
The half-life of total SOD1 protein will be determined in ALS patients using peptides that do not contain SOD1 mutation. The Investigators will analyze the kinetics of wild type SOD1 protein separately from mutant SOD1 protein using the mutation-containing peptide in order to determine differences in half-life using the stable isotope labeling kinetics (SILK) method of mass spectrometry.
Measured: Assessed over 121 days
Secondary outcomes (2)
ALS Functional Rating Scale-Revised (ALSFRS-R)
12 questions about patient's ability to function in certain activities of daily living. Each question is out of 4 with 4 being normal and 0 being completely impaired.
Measured: Baseline and weeks 1,2, 4, 9 and 17
Slow Vital Capacity (SVC)
Measurement of the maximum amount of air that can be exhaled following a deep breath.
Measured: Baseline and weeks 1,2, 4, 9 and 17
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2018
- Study startDec 2012
- Primary completionDec 2025 (estimated)
- Study completionDec 2026 (estimated)
Why it stopped: COVID-19 pandemic
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, FamilialStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 86 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Massachusetts General Hospital
- Responsible party
- Principal investigator, Timothy M. Miller, MD, PhD, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03449212
- Sponsor's protocol ID
- SOD1-001
- Status last verified
- Jul 2024
- First submitted
- 6 Feb 2018
- Last updated
- 25 Jul 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Ly CV, Ireland MD, Self WK, Bollinger J, Jockel-Balsarotti J, Herzog H, Allred P, Miller L, Doyle M, Anez-Bruzual I, Trikamji B, Hyman T, Kung T, Nicholson K, Bucelli RC, Patterson BW, Bateman RJ, Miller TM. Protein kinetics of superoxide dismutase-1 in familial and sporadic amyotrophic lateral sclerosis. Ann Clin Transl Neurol. 2023 Jun;10(6):1012-1024. doi: 10.1002/acn3.51784. Epub 2023 Apr 29.
PubMed 37119480
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- SOD1 Kinetics Measurements in ALS Patients
- ClinicalTrials.gov ID
- NCT03449212
- Acronym / sponsor ID
- SOD1-001
- Keywords
- SOD1, Amyotrophic Lateral Sclerosis, ALS, Kinetics, Amyotrophic Lateral Sclerosis, Familial, Amyotrophic Lateral Sclerosis, Sporadic
- Study type
- Observational
- Recruitment status
- SuspendedReason stopped: COVID-19 pandemic
- Enrolment
- 86 participants (estimated)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- Massachusetts General Hospital
- Study start
- Dec 2012 (actual)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 28 Feb 2018 (actual)
- 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.
Washington University in St. Louis is seeking participants with ALS for a study to determine the half-life of the protein SOD1 in the cerebral spinal fluid. Mutations in the SOD1 gene are known to cause some forms of familial ALS. Researchers are developing a treatment to reduce the level of SOD1 in familial ALS, but need to know more about how long SOD1 stays in the body ("half-life") to help determine if the new treatment is effective.
Detailed description
Background: Novel targeted therapeutic strategies are being developed for genetic subsets of ALS, such as those caused by dominantly inherited mutations in the superoxide dismutase 1 gene (SOD1). Investigators have developed an antisense oligonucleotide (ASO) inhibitor of SOD1 biosynthesis for ALS patients who carry mutations in SOD1. This ASO is now ready for clinical trial (ClinicalTrials.gov #NCT02623699). The initial success of the ASO will depend on showing a pharmacodynamics result on SOD1 in participants, and thus a key challenge in applying this targeted therapy involves rigorous examination of pharmacodynamics markers.
The Investigator's previous data suggest that SOD1 in the cerebral spinal fluid (CSF) will be an excellent pharmacodynamics marker for an SOD1-focused therapeutic approach. However, one of the central missing components in understanding SOD1 as a marker is SOD1 CSF half-life data. The half-life of this protein will aid in clinical trial planning since half-life influences the amount of SOD1 protein reduction by ASO and thus dictates the optimal timing of drug administration and CSF collection for pharmacodynamics measures.
Objectives:
- Enroll a total of 86 ALS participants
- Determine the kinetics for total SOD1 protein, as well as the wild type and mutant protein separately
- Determine this in patients with known SOD1 mutation as well as sporadic ALS patients Eligibility
- Adults over age 18
- fALS with confirmed genetic testing showing a mutation in the SOD1 gene; asymptomatic SOD1 gene carriers and sporadic ALS patients.
Measures: The key outcome of this study is to determine the half-life of the SOD1 protein in symptomatic and asymptomatic ALS patients which will provide critical information to inform future therapeutic studies in ALS. For ALS patients, The Investigators will also perform Slow Vital Capacity testing and the ALSFRS-R at the screening visit and at each lumbar puncture visit.
Measures: Participants will have up to 7 in-person visits over 4 months. The study involves labeling or marking SOD1 with a special type of leucine. Leucine is an essential amino acid that is found in the foods we eat. This method involves an overnight stay for a 16 hour intravenous infusion of labeled leucine along with a collection blood and urine followed by 5 lumbar punctures scheduled over the period of 4 months.
At each subsequent visit, subjects will undergo a blood draw, urine collection, lumbar puncture, a questionnaire (ALS Functional Rating Scale) which measures motor function, and a breathing test to determine Slow Vital Capacity (SVC) measurements.
Analysis: In addition to determining the half-life of the SOD1 protein in ALS patients, the Investigators will also analyze the kinetics of wild type SOD1 protein separately from mutant SOD1 protein to determine differences in half life. The Investigators will also compare CSF Tau half-life between ALS patients and controls as a disease specificity control. The Investigators hope to correlate this data with clinical measures which may reveal other important hypotheses regarding SOD1 kinetic rates and disease manifestations.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| SOD1 ALS | – | – |
| Sporadic ALS | – | – |
| Asymptomatic SOD1 gene carriers | – | – |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Known SOD1 positive ALS status, sporadic ALS and SOD1 positive carriers (non-ALS).
Key inclusion criteria (5 listed)
- Males or females of any race aged 18 or older
- Positive for SOD1 mutation (SOD1 ALS only)
- Diagnosed with Definite, Probable or Possible ALS in accordance with El Escorial criteria (ALS and SOD1 Positive ALS only)
- Able to hold position and breathe comfortably for the duration of the LP procedure as determined by the LP physician or Nurse Practitioner
- Subjects must be able to provide informed consent
Key exclusion criteria (12 listed)
- Invasive ventilator dependence, such as tracheostomy
- Medically unable to undergo lumbar puncture (LP) as determined by the investigator (i.e.,bleeding disorder, allergy to local anesthetics, a skin infection at or near the LP site, or evidence of high intracranial pressure).
- Any active dermatologic disease.
- Any connective tissue disease including systemic lupus erythematous, Sjögren's syndrome, scleroderma or mixed connective tissue disease.
- Any known or suspected abnormal CSF pressure or intracranial/intraspinal tumors.
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
The primary outcome measurement will be the determination of the SOD1 half-life in the CSF of each subject.
Time frame: Assessed over 121 days
The half-life of total SOD1 protein will be determined in ALS patients using peptides that do not contain SOD1 mutation. The Investigators will analyze the kinetics of wild type SOD1 protein separately from mutant SOD1 protein using the mutation-containing peptide in order to determine differences in half-life using the stable isotope labeling kinetics (SILK) method of mass spectrometry.
2 secondary outcomes
ALS Functional Rating Scale-Revised (ALSFRS-R)
Time frame: Baseline and weeks 1,2, 4, 9 and 17
Slow Vital Capacity (SVC)
Time frame: Baseline and weeks 1,2, 4, 9 and 17
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2024.
- Results publication: PubMed 37119480Ly CV, Ireland MD, Self WK, Bollinger J, Jockel-Balsarotti J, Herzog H, Allred P, Miller L, Doyle M, Anez-Bruzual I, Trikamji B, Hyman T, Kung T, Nicholson K, Bucelli RC, Patterson BW, Bateman RJ, Miller TM. Protein kinetics of superoxide dismutase-1 in familial and sporadic amyotrophic lateral sclerosis. Ann Clin Transl Neurol. 2023 Jun;10(6):1012-1024. doi: 10.1002/acn3.51784. Epub 2023 Apr 29.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Amyotrophic Lateral Sclerosis, Familial and Amyotrophic Lateral Sclerosis, Sporadic, run by Washington University School of Medicine 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 5 inclusion and 12 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: paused, as of the sponsor's last update on 25 Jul 2024. 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?
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?
The primary outcome measurement will be the determination of the SOD1 half-life in the CSF of each subject. (time frame: Assessed over 121 days). 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 NCT03449212, 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 25 Jul 2024.