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Genetic Risk Factors for Multi-system Inflammatory Syndrome in Children and Pediatric Post COVID Condition (GRIP)

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ClinicalTrials.gov Identifier: NCT05722717
Recruitment Status : Recruiting
First Posted : February 10, 2023
Last Update Posted : February 10, 2023
Sponsor:
Collaborators:
ZonMw: The Netherlands Organisation for Health Research and Development
University Medical Center Groningen
UMC Utrecht
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Information provided by (Responsible Party):
epbuddingh, Leiden University Medical Center

Tracking Information
First Submitted Date February 9, 2023
First Posted Date February 10, 2023
Last Update Posted Date February 10, 2023
Actual Study Start Date June 28, 2022
Estimated Primary Completion Date January 31, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: February 9, 2023)		 Quantity and quality of genetic variants in immunological genes between study groups. [ Time Frame: 2 year ]
We want to quantify how many immunogenic variants are found between the groups and identify which variants/genes these are.
Original Primary Outcome Measures Same as current
Change History No Changes Posted
Current Secondary Outcome Measures
 (submitted: February 9, 2023)		 Correlate genetic findings with clinical characteristics [ Time Frame: 2 year ]
We want to connect the data found during genetic testing with multiple clinical characteristics already collected in previous studies.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Genetic Risk Factors for Multi-system Inflammatory Syndrome in Children and Pediatric Post COVID Condition
Official Title Genetic Risk Factors for Multi-system Inflammatory Syndrome in Children and Pediatric Post COVID Condition
Brief Summary We will perform Whole Exome Sequencing on DNA from saliva. We will include: Children with a history of MIS-C; children with post-COVID condition; and controls in order to identify rare, high impact genetic variants in immunological genes and pathways in children with a history of MIS-C or pediatric post-COVID condition.
Detailed Description

Rationale:

Following infection with SARS-CoV-2, some children develop the potentially life-threatening disease Multi-System Inflammatory Syndrome in Children (MIS-C) and some children develop post-COVID condition (formerly 'long COVID'). It is unknown why some children develop severe or prolonged symptoms after SARS-CoV-2 infection, while most children have asymptomatic or mild disease. We hypothesize that rare variants in genes associated with the immune system predispose children to develop MIS-C or post-COVID condition after infection with SARS-CoV-2.

Objective:

Primary objective: To identify rare, high impact genetic variants in immunological genes and pathways in children with a history of MIS-C or pediatric post-COVID condition.

Secondary objectives: To analyze the clinical characteristics and long-term effects of pediatric COVID-19 and MIS-C. To characterize the functional and clinical impact of genetic variants in MIS-C and post-COVID condition and identify targets for therapy.

Study design:

We will do an observational study. We will perform Whole Exome Sequencing (WES) using Next Generation Sequencing (NGS) on DNA from blood or saliva. We will include: (1) MIS-C cases: Children with a history of MIS-C; (2) post-COVID condition cases: Children with post-COVID condition; and (3) Controls: SARS-CoV-2 exposed age-matched control group: children who were infected with SARS-CoV-2 but did not develop moderate to severe COVID-19, MIS-C or post-COVID condition.

Study population:

Children 0-19 years old with a history of MIS-C (n=100), post-COVID condition (n=100), or uncomplicated SARS-CoV-2 infection (n=200).

Main study parameters/endpoints:

  1. To evaluate if some children with MIS-C or post-COVID condition have an inborn error of immunity by determining the presence of pathogenic or likely pathogenic variants in immunological genes
  2. To evaluate if a larger proportion of cases with MIS-C or post-COVID condition have rare and presumably deleterious variants in immunological genes than children with an asymptomatic or mild infection
Study Type Observational
Study Design Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Saliva
Sampling Method Non-Probability Sample
Study Population Children with a history of MIS-C or Post-COVID Condition and children with a known SARS-CoV-2 infection without severe disease course.
Condition
  • COVID-19
  • Post-Acute COVID-19
  • Post-Acute COVID19 Syndrome
  • Multi-System Inflammatory Syndrome in Children
  • Pediatric Inflammatory Multisystem Syndrome
  • Post COVID-19 Condition
  • Post-COVID-19 Syndrome
Intervention Genetic: Saliva collection at home
Children (with help of their parents) collect their saliva with a saliva collection kit which they send to our research center.
Study Groups/Cohorts
  • MIS-C
    Children with a history of MIS-C: as defined according to WHO criteria, who were 0-18 at the time of MIS-C.
    Intervention: Genetic: Saliva collection at home
  • Post COVID-Condition
    Children with post-COVID condition who were 0-18 at the time of SARS-CoV-2 infection: as defined according to the WHO case definition.
    Intervention: Genetic: Saliva collection at home
  • Control
    'Exposed' control group: children with a history of proven SARS-CoV-2 infection (RT-PCR, antigen test or serology positive) who were 0-18 at the time of SARS-CoV-2 infection.
    Intervention: Genetic: Saliva collection at home
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 Recruiting
Estimated Enrollment
 (submitted: February 9, 2023)		 400
Original Estimated Enrollment Same as current
Estimated Study Completion Date January 31, 2024
Estimated Primary Completion Date January 31, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  1. Children (<19 years) with a history of MIS-C: as defined according to WHO criteria.
  2. Children (<19 years) with post-COVID condition: as defined according to the WHO case definition. This includes a history of probable or confirmed prior SARS-CoV-2 infection, with signs and symptoms (including fatigue, shortness of breath, cognitive dysfunction) that are present after 12 weeks, last at least 2 months, have an impact on daily functioning and are not explained by an alternative diagnosis.
  3. 'Exposed' control group: children (<19 years of age): a history of proven SARS-CoV-2 infection (RT-PCR, antigen test or serology positive). If the child has been vaccinated against SARS-CoV-2, the first documented infection must have been prior to the vaccination.

Exclusion Criteria:

  1. No informed consent
  2. Group 1 (MIS-C): no specific exclusion criteria

  3. Group 2 (post-COVID condition): other plausible cause of symptoms AND/OR a history compatible with chronic fatigue syndrome prior to infection with SARS-CoV-2.

    Children with a history of MIS-C who suffer prolonged signs and symptoms will be included in the MIS-C group.

  4. Group 3 ('exposed' control group): MIS-C or post-COVID condition; AND/OR Moderate or severe course of COVID-19, as defined in the COPP-study (N20.043) (need for supplemental oxygen and/or intensive care admission because of COVID-19 and/or death) AND/OR first degree relative with long COVID or MIS-C.
Sex/Gender
Sexes Eligible for Study: All
Ages 0 Months to 19 Years   (Child, Adult)
Accepts Healthy Volunteers Yes
Contacts
Contact: Adam J Tulling, MD 629843439 ext +31 a.j.tulling@lumc.nl
Contact: Emmeline P Buddingh, MD, PhD 715262822 ext +31 E.P.Buddingh@lumc.nl
Listed Location Countries Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number NCT05722717
Other Study ID Numbers NL80853.058.22
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 epbuddingh, Leiden University Medical Center
Original Responsible Party Same as current
Current Study Sponsor Leiden University Medical Center
Original Study Sponsor Same as current
Collaborators
  • ZonMw: The Netherlands Organisation for Health Research and Development
  • University Medical Center Groningen
  • UMC Utrecht
  • Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Investigators
Principal Investigator: Emmeline P Buddingh, MD, PhD Leiden University Medical Center
PRS Account Leiden University Medical Center
Verification Date February 2023