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Longitudinal Study of Innate Lymphoid Cells in Peripheral Blood in ALS

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ClinicalTrials.gov Identifier: NCT03090932
Recruitment Status : Terminated (Study recruitment, data and sample collection terminated due to COVID-19. Data analysis continues.)
First Posted : March 27, 2017
Last Update Posted : January 12, 2022
Sponsor:
Information provided by (Responsible Party):
Benjamin Murdock, University of Michigan

Tracking Information
First Submitted Date March 14, 2017
First Posted Date March 27, 2017
Last Update Posted Date January 12, 2022
Actual Study Start Date January 18, 2016
Actual Primary Completion Date November 13, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: December 17, 2020)
Total number of classical NK (natural killer) cells; total number of CD3+ CD4+ CD8+ cells [ Time Frame: Every 28 days (+/- 5 days) for 12 total visits over 36 months ]
Total number of classical NK cells; total number of CD3+ CD4+ CD8+ cells
Original Primary Outcome Measures
 (submitted: March 20, 2017)
Total number of classical NK (natural killer) cells; total number of CD3+ CD4+ CD8+ cells [ Time Frame: Every 28 days (+/- 3 days) for 12 months ]
Total number of classical NK cells; total number of CD3+ CD4+ CD8+ cells
Change History
Current Secondary Outcome Measures
 (submitted: December 17, 2020)
Cytokine expression [ Time Frame: Every 28 days (+/- 5 days) for 12 total visits over 36 months ]
Cytokine expression levels of these cell populations using qPCR, RNA-Seq, or Luminex.
Original Secondary Outcome Measures
 (submitted: March 20, 2017)
Cytokine expression [ Time Frame: Every 28 days (+/- 3 days) for 12 months ]
Cytokine expression levels of these cell populations using qPCR, RNA-Seq, or Luminex.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Longitudinal Study of Innate Lymphoid Cells in Peripheral Blood in ALS
Official Title Longitudinal Study of Innate Lymphoid Cells in Peripheral Blood in ALS
Brief Summary Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by progressive muscle weakness and eventual death. Studies demonstrate that the immune system plays a key role in ALS progression; however, the role of the immune system is unclear, as various aspects can play both a beneficial and detrimental role in the disease course. Attempts to universally suppress the immune system in ALS patients have at best had negligible effects on progression or at worst accelerated the disease. Thus, there is a critical need to identify immune cell populations to serve as biomarkers and therapeutic targets.
Detailed Description

Application - HUM00107546

Study Title:

Longitudinal Study of Innate Lymphoid Cells in Peripheral Blood in ALS

Full Study Title:

Longitudinal Study of Innate Lymphoid Cells in Peripheral Blood in ALS

If there are other U-M studies related to this project, enter the eResearch ID number (HUM#) or IRBMED Legacy study number. Examples of related projects include, but are not limited to:

00028826 - Epidemological Risk Factors and The Genetics of ALS

Principal Investigator:

  • Benjamin Murdock, PhD

Study Team Members:

  • Eva Feldman, MD, PhD Co-Investigator
  • Stephen Goutman, MD Co-Investigator
  • Claudia Figueroa-Romero, Research Investigator
  • Crystal Pacut, Biorepository Coordinator
  • Jayna Duell, Study Coordinator
  • Blake Swihart, Study Coordinator
  • Adam Patterson, Biostatistician

Project Summary:

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by progressive muscle weakness and eventual death. Studies demonstrate that the immune system plays a key role in ALS progression; however, the role of the immune system is unclear, as various aspects can play both a beneficial and detrimental role in the disease course. Attempts to universally suppress the immune system in ALS patients have at best had negligible effects on progression or at worst accelerated the disease. Alternatively, augmenting or depleting specific immune cell populations in ALS mouse models alters the disease course and slows progression. Thus, there is a critical need to identify immune cell populations to serve as biomarkers and therapeutic targets.

Neuroinflammation is a hallmark of ALS in both human patients and mouse models. While clinical symptoms result from motor neuron degeneration, it is becoming increasingly clear that the immune system plays a key role in pathology. A variety of insults give rise to identical immune responses which go on to produce the characteristic clinical and histopathological manifestations of motor neuron disease. This makes the immune system an attractive target for therapeutics, as the wide variety of potential ALS sources all funnel through a common immunological pathway over the course of disease. The investigators recent studies have demonstrated that ALS patients have increased levels of several subpopulations of innate lymphoid cells (ILCs) in their peripheral blood. A subset of patients has ILC levels 5-10 times greater than those found in healthy control patients. The differences seen in the ILC levels in peripheral blood are much greater differences seen in other immune cell populations during ALS. Thus, these cell populations are attractive candidates for use as biomarkers or therapeutic targets.

The proposed study can be broken into three broad phases which will applicable to each patient: recruitment, sample collection, and analysis. Following diagnosis of disease, ALS patients who live within 1 hour of the University of Michigan will be called by our clinical coordinator and enrolled in the study (recruitment). Following enrollment in the study, each of the patients will be visited once every 28 ± 5 days for a year after the initial visit by a Michigan Institute for Clinical & Health Research (MICHR) clinical research unit; this unit will take 20 ml of blood per patient. Samples will then be returned to the University of Michigan. ILCs will be isolated from peripheral blood using fluorescence-activated cell sorting (FACS) and the mRNA of each ILC population will be collected and cytokine production analyzed using multiplex (analysis). On the day of collection, a clinician or clinical coordinator from the University of Michigan Comprehensive ALS Clinic (UMCAC) will contact the patient to complete an ALSFRS-R questionnaire to assess the physical deterioration of the patients.

The study will also incorporate control subjects. The control subjects will have blood taken once a month for 12 total visits over 36 months, but will not complete the ALSFRS-R questionnaire as they will not have been diagnosed with ALS and therefore the questionnaire does not fit; 20ml of blood will be taken per visit.

Subjects need to live within approximately 60 miles of the University of Michigan.

Study Type Observational
Study Design Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Innate lymphoid cells from whole blood
Sampling Method Non-Probability Sample
Study Population ALS patients (200) and matched controls (75)
Condition Amyotrophic Lateral Sclerosis
Intervention Other: Blood draw
Research subjects will have two tubes of blood drawn, approximately 20mL.
Study Groups/Cohorts Not Provided
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 Terminated
Actual Enrollment
 (submitted: December 22, 2021)
66
Original Estimated Enrollment
 (submitted: March 20, 2017)
25
Actual Study Completion Date November 13, 2020
Actual Primary Completion Date November 13, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Age 18 years or older.
  • Clinically definite, probable, probable laboratory supported, or possible ALS by El Escorial criteria
  • Fluency in English at the 6th grade level or higher.
  • Able to communicate sufficiently well by speaking
  • Able to communicate over the phone.
  • Capable of providing informed consent.
  • Lives geographically accessible to the University of Michigan

Exclusion Criteria:

  • Unable to provide informed consent.
  • Clinically significant dementia, as judged by the site investigator.
  • Other neurological or psychiatric disorders which are expected to impair cognitive function.
  • Other serious and uncontrolled medical disorders.
  • History of autoimmune disease.
  • Use of prednisone, IVIG, or immunosuppression within the last 12 months.
  • Not geographically accessible to the University of Michigan
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 80 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
Removed Location Countries  
 
Administrative Information
NCT Number NCT03090932
Other Study ID Numbers HUM00107546
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: Undecided
Current Responsible Party Benjamin Murdock, University of Michigan
Original Responsible Party Benjamin Murdock, University of Michigan, Post-Doctoral Fellow
Current Study Sponsor University of Michigan
Original Study Sponsor Same as current
Collaborators Not Provided
Investigators
Principal Investigator: Ben Murdock, PhD University of Michigan
PRS Account University of Michigan
Verification Date December 2021