SOD1 Kinetics Measurements in ALS Patients

NCT03449212 | Suspended DMC

• 1 other identifier: SOD1-001
• Study Type: observational
• Target: 86
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Amyotrophic Lateral Sclerosis, Familial; Amyotrophic Lateral Sclerosis, Sporadic

Keywords

SOD1; Amyotrophic Lateral Sclerosis; ALS; Kinetics; Amyotrophic Lateral Sclerosis, Familial; Amyotrophic Lateral Sclerosis, Sporadic

Outcome Measures

Primary Outcomes (1)

• 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.

  Assessed over 121 days

Secondary Outcomes (2)

• ALS Functional Rating Scale-Revised (ALSFRS-R)

  Baseline and weeks 1,2, 4, 9 and 17

• Slow Vital Capacity (SVC)

  Baseline and weeks 1,2, 4, 9 and 17

Study Arms (3)

SOD1 ALS

Sporadic ALS

Asymptomatic SOD1 gene carriers

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Known SOD1 positive ALS status, sporadic ALS and SOD1 positive carriers (non-ALS).

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Massachusetts General Hospital: collaborator

Study Sites (1)

Washington University in St. Louis

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

• 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.

  PMID: 37119480 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Plasma, Red Blood Cell (RBC), Cerebral Spinal Fluid (CSF), urine

MeSH Terms

Conditions

Amyotrophic lateral sclerosis 1; Amyotrophic Lateral Sclerosis

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: David Clayson Professor of Neurology

Study Record Dates

• First Submitted: February 6, 2018
• First Posted: February 28, 2018
• Study Start: December 1, 2012
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: July 25, 2024

Record last verified: 2024-07

Locations

US (1)