Analysis of Post-Translational Modifications of a Critical Protein Implicated in Amyotrophic Lateral Sclerosis (SOD1)

• ClinicalTrials.gov Identifier: NCT02228915
• Recruitment Status: Completed
• First Posted: August 29, 2014
• Last Update Posted: October 17, 2018
• Sponsor: University of North Carolina, Chapel Hill
• Information provided by (Responsible Party): University of North Carolina, Chapel Hill

Tracking Information

• First Submitted Date: August 27, 2014
• First Posted Date: August 29, 2014
• Last Update Posted Date: October 17, 2018
• Actual Study Start Date: August 2014
• Actual Primary Completion Date: October 14, 2018 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: August 28, 2014): Post-translational modifications (PTMs) of Cu/Zn superoxide dismutase 1 [ Time Frame: 6 months ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Analysis of Post-Translational Modifications of a Critical Protein Implicated in Amyotrophic Lateral Sclerosis
• Official Title: Analysis of Post-Translational Modifications of a Critical Protein Implicated in Amyotrophic Lateral Sclerosis
• Brief Summary: The purpose of this research study is to discover and quantitate the differences in post-translational modifications found in the Cu, Zn superoxide dismutase (SOD1) of patients with amyotrophic lateral sclerosis (ALS) as compared to healthy individuals. SOD1 is a known genetic cause of ALS. With certain mutations, SOD1 gains a toxic function which leads to motor neuron death.
• Detailed Description: Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease in which mutations in human Cu, Zn Superoxide Dismutase (SOD1) have been identified as a cause of familial ALS (FALS) cases.1-2 It has been shown that mutant SOD1 develops a novel toxic function through experiments demonstrating that many disease mutants maintain enzymatic activity, SOD1-null mice do not exhibit ALS symptoms, and co-expressed wild type protein does not rescue the disease-state.7-11 The majority of cases, however, are not caused directly by mutations of SOD1, instead being caused by a poorly understood interplay of several genes as well as environmental factors, which is often referred to as sporadic ALS (SALS).3 It has been found that FALS and SALS share similar pathology. 4-6 The hSOD1 protein aggregates characteristic of FALS have also been found in SALS patients, furthering the evidence that hSOD1 has an important role in the etiology of ALS in sporadic ALS patients.16-19 The exact mechanism of SOD1-associated toxicity has not yet been elucidated though many disease mutants have been shown to destabilize the SOD1 dimer. In this study we aim to compare the levels of SOD1 post-tra slational modifications in ALS patients to levels in healthy donors and to determine if there are distinct patterns of protein glutathionylation or phosphorylation. Our overall goal is to elucidate a direct mechanism of toxicity in SALS as well as identify potentially critical triggers
• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

A portion of this sample will be stored for future use in study of ALS and how the critical protien affects the disease progression long term. This sample will be stored de-identified; therefore will not be linked to any identifying informaton about the subject. Sample will be stored at the UNC biophysics and Biochemistry lab indefinitely

• Sampling Method: Probability Sample
• Study Population: SALS patients SOD1 associated FALS patients Healthy control
• Condition: ALS
• Intervention: Not Provided
• Study Groups/Cohorts: Not Provided
• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 16, 2018): 21
• Original Estimated Enrollment (submitted: August 28, 2014): 30
• Actual Study Completion Date: October 16, 2018
• Actual Primary Completion Date: October 14, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• SALS patients
• SOD1 associated FALS patients
• Healthy control

Exclusion Criteria: none

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 99 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02228915
• Other Study ID Numbers: 14-1780
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: University of North Carolina, Chapel Hill
• Original Responsible Party: Chafic Karam, MD, University of North Carolina, Chapel Hill, Assistant Professor of Neurology
• Current Study Sponsor: University of North Carolina, Chapel Hill
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Chafic Karam, MD; University of North Carolina, Chapel Hill
• Principal Investigator: Nikolay V Dokholyan, PhD; UNC

• PRS Account: University of North Carolina, Chapel Hill
• Verification Date: November 2017