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Understanding Clinical Phenotype and Collecting Biomarker Samples in C9ORF72 ALS

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02686268
Recruitment Status : Completed
First Posted : February 19, 2016
Last Update Posted : October 4, 2018
Sponsor:
Collaborators:
Cedars-Sinai Medical Center
UMC Utrecht
Johns Hopkins University
Massachusetts General Hospital
University of Massachusetts, Amherst
Biogen
ALS Association
Columbia University
Information provided by (Responsible Party):
Timothy M. Miller, MD, PhD, Washington University School of Medicine

Tracking Information
First Submitted Date February 11, 2016
First Posted Date February 19, 2016
Last Update Posted Date October 4, 2018
Study Start Date February 2015
Actual Primary Completion Date December 31, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: January 5, 2017)
Collection of clinical data and biomarker samples [ Time Frame: December 2017 ]
The primary outcome measures will be the collection of clinical data (ALSFRS, ALS-CBS and SVC) to determine rates of disease progression and collection of biomarkers samples (blood, CSF) to be correlated with the clinical measures.
Original Primary Outcome Measures
 (submitted: February 18, 2016)
Collection of clinical data and biomarker samples [ Time Frame: February 2018 ]
The primary outcome measures will be the collection of clinical data (ALSFRS, ALS-CBS and SVC) to determine rates of disease progression and collection of biomarkers samples (blood, CSF) to be correlated with the clinical measures.
Change History Complete list of historical versions of study NCT02686268 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: January 5, 2017)
Correlation of repeat expansion size with clinical outcome measures and determination of C9ORF72 patients eligibility for clinical trials [ Time Frame: December 2017 ]
The secondary outcome measures include determination of the C9ORF72 hexanucleotide repeat expansion size and correlating this with the outcome measures of disease progression collected (ALSFRS-R/month, decrease in SVC/month and ALS Cognitive Screen) and determination of C9ORF72 ALS patients that may be available for a clinical trial.
Original Secondary Outcome Measures
 (submitted: February 18, 2016)
Correlation of repeat expansion size with clinical outcome measures and determination of C9ORF72 patients eligibility for clinical trials [ Time Frame: February 2018 ]
The secondary outcome measures include determination of the C9ORF72 hexanucleotide repeat expansion size and correlating this with the outcome measures of disease progression collected (ALSFRS-R/month, decrease in SVC/month and ALS Cognitive Screen) and determination of C9ORF72 ALS patients that may be available for a clinical trial.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Understanding Clinical Phenotype and Collecting Biomarker Samples in C9ORF72 ALS
Official Title Understanding Clinical Phenotype and Collecting Biomarker Samples in C9ORF72 ALS
Brief Summary This research study is being performed to better understand a specific form of Amyotrophic Lateral Sclerosis (ALS) caused by a mutation (or abnormality) of the C9ORF72 gene. This mutation is the most common genetic cause of ALS, and is present in 40% of ALS patients with a family history of ALS and 5-10% of ALS patients without a family history of ALS.
Detailed Description

Individuals diagnosed with ALS, who are confirmed to carry the Chromosome 9 Open Reading Frame 72 (C9ORF72) gene mutation by CLIA-certified lab results, are eligible for enrollment. Researchers want to understand the natural history of C9ORF72 related ALS in terms of measures of rate of progression as well as understanding how the size of the hexanucleotide repeat expansion influences disease parameters. The investigators hope that the intense study of patients with the C9ORF72 mutation will ultimately help us develop treatments for this common form of ALS.

Objectives:

  • Enroll a total of 120 C9ORF72 ALS participants with known mutation at the time of enrollment.
  • Determine the C9ORF72 hexanucleotide repeat expansion size in all subjects
  • Define ALS disease course
  • Determine to what degree the disease course correlates with expansion size
  • Collect biomarker samples (blood, DNA and CSF)

Eligibility:

- Adults over age 18 with known C9ORF72 ALS status

Design:

Participants will have up to 9 in-person visits (this includes two Optional visits for lumbar puncture procedures) and 5 telephone interviews over 3 years. Each in-person visit may be tied to a regular clinic visit if subject is local (except for the optional lumbar puncture visits) or if the subject is from out of town one initial visit can be set up with all other visits performed via a telephone call and medical records review.

At each in town visit, subjects will undergo a blood draw (optional lumbar puncture) and two questionnaires (ALS Functional Rating Scale - revised ALSFRS-R) which measures motor function and the ALS-Cognitive Behavioral Screen (ALS-CBS) which will detect signs of Frontal Temporal Dementia and a breathing test to determine Slow Vital Capacity (SVC) measurements.

For out of town subjects - blood draws can be scheduled locally and sent to the study site for analysis. The ALSFRS-R can be performed over the phone along with other study related questions.

The C9ORF72 mutation is called a "dominant" mutation, which means that their children have a 50% chance of inheriting the gene. Most people who inherit the C9ORF72 mutation will develop either ALS or the related disease called fronto-temporal dementia. However, it may be possible for someone to test positive for the C9ORF72 gene mutation and never develop symptoms. Furthermore, in addition to C9ORF72, there are many other gene mutations that can cause ALS. This study will not test these other genes, and therefore a negative test result for the C9ORF72 mutation will not exclude the possibility that you have a heritable form of ALS.

In order to understand the natural history of C9ORF72 related ALS in terms of measures of rate of progression, the investigators need to understand how the size of the hexanucleotide repeat expansion influences disease parameters. A C9ORF72-focused clinical trial defining an accurate historical control population, will be critical since there may not be enough subjects for a placebo controlled trial. To be ready for upcoming therapeutic trials, the investigators need to start the detailed characterization of the C9ORF72 patients immediately.

Study Type Observational
Study Design Observational Model: Case-Only
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Whole blood (DNA, Southern Blots), Serum, PBMCs (for reprogramming into iPSCs), and Cerebral Spinal Fluid (CSF)
Sampling Method Non-Probability Sample
Study Population Known positive C9ORF72 ALS status upon enrollment
Condition C9ORF72 Amyotrophic Lateral Sclerosis (ALS)
Intervention Not Provided
Study Groups/Cohorts Individuals diagnosed with known positive C9ORF72 ALS
Individuals diagnosed with known positive C9ORF72 ALS
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: February 6, 2018)
128
Original Estimated Enrollment
 (submitted: February 18, 2016)
80
Actual Study Completion Date October 2, 2018
Actual Primary Completion Date December 31, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion:

  1. Males or females of any race aged 18 or older
  2. Known positive C9ORF72 ALS status via CLIA-certified lab results.
  3. Capable of providing informed consent and following study procedures. In the event that an individual lacks the ability to provide informed consent, informed consent may be sought from the individual's legal, surrogate representative.
  4. Geographically accessible to the site.

Exclusion:

  1. Geographically inaccessible to the site
  2. C9ORF72 ALS negative via CLIA-certified lab results
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Netherlands,   United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT02686268
Other Study ID Numbers 14LGCA123
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement
Plan to Share IPD: No
Plan Description:

The study design has a robust plan to share de-identified data (but personally identifiable data will not be shared). When study information is shared, it will be "de-identified", meaning that the study will remove all personal identifiers so that all collected data and samples are stored under a unique subject ID study code ("coded"). In other words, the study has been designed to keep personal details separate from all samples and study information.

The results of this trial will be published in peer-reviewed journals. No personal identifiers will be included.

Responsible Party Timothy M. Miller, MD, PhD, Washington University School of Medicine
Study Sponsor Washington University School of Medicine
Collaborators
  • Cedars-Sinai Medical Center
  • UMC Utrecht
  • Johns Hopkins University
  • Massachusetts General Hospital
  • University of Massachusetts, Amherst
  • Biogen
  • ALS Association
  • Columbia University
Investigators
Principal Investigator: Timothy M Miller, MD, PhD Washington University School of Medicine
PRS Account Washington University School of Medicine
Verification Date October 2018