COVID-19GRIPNCT05722717
Genetic Risk Factors for Multi-system Inflammatory Syndrome in Children and Pediatric Post COVID Condition
An observational study of COVID-19 and Post-Acute COVID-19, run by Leiden University Medical Center at 1 site in Netherlands.
Trial 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… Read more about this study
- Who is it for?
- Ages 0 months to 19 yearsHealthy volunteers can take part
- Conditions the study is for
- COVID-19, Post-Acute COVID-19, Post-Acute COVID19 Syndrome
- What is being tested?
- Saliva collection at home
- How many people
- 400 participants
- Where
- 1 siteNetherlands
- Study dates
- 28 Jun 2022to 31 Jan 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 months to 19 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
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.
Who may be able to join
- Children (<19 years) with a history of MIS-C: as defined according to WHO criteria.
- 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.
- '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.
Who cannot join
- No informed consent
- Group 1 (MIS-C): no specific exclusion criteria
- 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.
- 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.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
Leiden University Medical Center
Leiden, South Holland, 2333ZA
Adam Tulling, MD, +31629843439, a.j.tulling@lumc.nl
About this study
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.
Read the 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:
- 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
- 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
- Conditions
- COVID-19, Post-Acute COVID-19, Post-Acute COVID19 Syndrome, Multi-System Inflammatory Syndrome in Children, Pediatric Inflammatory Multisystem Syndrome, Post COVID-19 Condition
- Being tested
- Saliva collection at home
- Keywords
- COVID-19, Post-COVID Condition, MIS-C, PIMS-TS
- Medical subject headings
- COVID-19, Post-Acute COVID-19 Syndrome, pediatric multisystem inflammatory disease, COVID-19 related
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Saliva collection at homeGenetic
Children (with help of their parents) collect their saliva with a saliva collection kit which they send to our research center.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Genetic: Saliva collection at home |
What is being measured
The primary outcome is the main question the study is designed to answer.
Quantity and quality of genetic variants in immunological genes between study groups.
We want to quantify how many immunogenic variants are found between the groups and identify which variants/genes these are.
Measured: 2 year
Secondary outcomes (1)
Correlate genetic findings with clinical characteristics
We want to connect the data found during genetic testing with multiple clinical characteristics already collected in previous studies.
Measured: 2 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2023
- Study start28 Jun 2022
- Primary completion31 Jan 2024 (estimated)
- Study completion31 Jan 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COVID-19Studies of the same condition, open and under way.
- More trials run by Leiden University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development, University Medical Center Groningen, UMC Utrecht, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Responsible party
- Principal investigator, epbuddingh, Leiden University Medical Center
- Investigators
- Emmeline P Buddingh, MD, PhD, Principal investigator, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05722717
- Sponsor's protocol ID
- NL80853.058.22
- Acronym
- GRIP
- Status last verified
- Feb 2023
- First submitted
- 9 Feb 2023
- Last updated
- 10 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genetic Risk Factors for Multi-system Inflammatory Syndrome in Children and Pediatric Post COVID Condition
- ClinicalTrials.gov ID
- NCT05722717
- Acronym / sponsor ID
- GRIP / NL80853.058.22
- Conditions
- COVID-19, Post-Acute COVID-19, Post-Acute COVID19 Syndrome, Multi-System Inflammatory Syndrome in Children, Pediatric Inflammatory Multisystem Syndrome, Post COVID-19 Condition
- Keywords
- COVID-19, Post-COVID Condition, MIS-C, PIMS-TS
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development, University Medical Center Groningen, UMC Utrecht, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Study start
- 28 Jun 2022 (actual)
- Primary completion
- 31 Jan 2024 (estimated)
- Study completion
- 31 Jan 2024 (estimated)
- First posted
- 10 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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
- 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 design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| MIS-C | – | Genetic: Saliva collection at homeChildren with a history of MIS-C: as defined according to WHO criteria, who were 0-18 at the time of MIS-C. |
| Post COVID-Condition | – | Genetic: Saliva collection at homeChildren with post-COVID condition who were 0-18 at the time of SARS-CoV-2 infection: as defined according to the WHO case definition. |
| Control | – | Genetic: Saliva collection at home'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. |
Who may qualify
- Ages
- 0 months to 19 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- 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.
Key inclusion criteria (3 listed)
- Children (<19 years) with a history of MIS-C: as defined according to WHO criteria.
- 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.
- '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.
Key exclusion criteria (5 listed)
- No informed consent
- Group 1 (MIS-C): no specific exclusion criteria
- 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.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Saliva collection at homeChildren (with help of their parents) collect their saliva with a saliva collection kit which they send to our research center. | Genetic | Control, MIS-C, Post COVID-Condition |
Primary outcome
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.
1 secondary outcome
Correlate genetic findings with clinical characteristics
Time frame: 2 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2023.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Emmeline P Buddingh, MD, PhD principal investigator
Leiden University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of COVID-19 and Post-Acute COVID-19, run by Leiden University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Adam J Tulling, MD (629843439 ext. +31, a.j.tulling@lumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Quantity and quality of genetic variants in immunological genes between study groups. (time frame: 2 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2023.