Clinical trial NCT05145348: Prospective Monitoring of Antibody Response Following COVID-19 Vaccination in Patients With Down Syndrome.
Official title: Prospective Monitoring of Antibody Response Following COVID-19 Vaccination in Patients With Down Syndrome
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Down Syndrome
SARS-CoV-2 Vaccination
Keywords: Down Syndrome
SARS-CoV-2 vaccination
Immuneresponse
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
name: National Institute for Public Health and the Environment (RIVM)
name: Stichting Downsyndroom (SDS)
name: Sanquin Research & Blood Bank Divisions
First posted: 2021-12-06
Enrollment: 640
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Down syndrome:

The patient population will either live in institutions or outside these facilitys depending on the cognitive functions and additional care needed. Children will mostly live with their parents. All participants will live in the Netherlands

Healthy control:

All healthy control participants will live in the Netherlands, no specific region.

Brief summary: The risk of severe course of SARS-CoV-2 infection in people with Down Syndrome is substantially increased. The risk of death is 3-10 fold higher than in healthy people. SARS-CoV-2 vaccines have been registered for adults and adolescents but none of them have been studied in people with Down Syndrome. Vaccine responses in people with Down Syndrome are known to be suboptimal. Therefor the objective of this study is to assess the immunogenicity of SARS-CoV-2 vaccination in people with Down syndrome.

To do so, the antibody response, cellulair and mucosal immuneresponse in people with Down syndrome after the SARS-CoV-2 vaccination will be evaluated and compared to healthy controls.

Detailed description: All participants will receive two vaccinations against COVID-19 according to the manufacturer's instructions as part of the Dutch SARS-CoV-2 vaccination program (GGD/RIVM). To assess the immune response after vaccination, blood samples will be collected at baseline (i.e. \<2 months prior to first vaccination (t=1)), 21-28 days after first vaccination and prior to second vaccination (t=2), 28 days (3-6 weeks) (t=3) and 12 (+/- 1) months (t=4) after the second vaccination. To evaluate haematological parameters, additional blood samples will be collected at baseline, 21-28 days after the first vaccination and 28 days after the second vaccination. Per visit/time-point maximum 60 ml blood will be drawn. In children the maximum amount of blood taken per visit/time-point will be 0,8 ml/kg up to 60 ml. In addition Mucosal Lining Fluid (MLF) samples will be collected at 28 days (3-6 weeks) (t=3) and 12 (+/- 1) months (t=4) after the second vaccination to evaluate the mucosal immune response after SARS-CoV-2 vaccination. In the pediatric part of the study Mucosal Lining Fluid (MLF) samples will be collected at all timepoints.

Although vaccine administration is not part of this study, vaccine type, batch number and dosing will be registered. This information will be obtained from the "COVID-vaccination information and monitoring system (CIMS)" of the RIVM.

Clinical course including the occurrence of COVID-19 will be monitored during the first year after vaccination. To evaluate vaccination related AEs, patients will be asked to collect solicited local and systemic AEs for 7 days after each vaccination using an online questionnaire, as vaccination related AEs are mainly expected in the first week after vaccination. The link to the online questionnaires will be sent to the emailaddress of the participants and/or their representative/carer. If the participants and/or their representative/carers are not able to fill out the diary online, they will be contacted by phone.

Although this study is not powered to detect differences in protection against COVID-19 between patients and controls, information on incidence of SARS-CoV-2 infection, outcome of COVID-19 will be collected up to 12 months after vaccination for descriptive purposes.

Eligibility criteria: Inclusion Criteria:

* Willing to receive routine COVID-19 vaccination with Pfizer, Moderna or AstraZeneca vaccine.
* Age: ≥12 years or \< 12 years once vaccine is recommended for routine use in the respective age group
* Either Down syndrome (DS) or household contacts without DS of participant with DS.

Exclusion Criteria:

Down syndrome cohort:

* History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (e.g. anaphylaxis) to any component of the study intervention(s).
* Organ transplant recipients
* Active malignancy or completion of treatment for malignancy in previous 3 months
* Infection with Human Immunodeficiency Virus (HIV)
* Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.

Healthy control cohort:

- As in Down Syndrome cohort

Plus:

* Active medical care for inherited or acquired immune deficiency
* Any severe comorbidity for which regular medical care is needed (e.g. heart failure, COPD, diabetes)

Primary outcomes:
measure: Antibody based immune response to vaccination against COVID-19 28 days (t=3) after the second vaccination as compared to controls.
timeFrame: 28 days after the second vaccination
Secondary outcomes:
measure: Longevity of SARS-CoV-2 specific antibodies
timeFrame: 1 year after the second vaccination
measure: SARS-CoV2 specific T cell response
timeFrame: Number of T cells will be measured at baseline, at 21-28 days after the first vaccination and at 28 days after the second vaccination
measure: Mucosal SARS-CoV-2 specific antibodies
timeFrame: Mucosal antibodies will be measured 28 days and 12 months after the second vaccination.
Other outcomes:
measure: Determination of fucosylation, sialylation, galactosylation and bisection of IgG in patients with a history of COVID-19.
timeFrame: All time points
measure: Age-specific T-cell immunophenotyping
timeFrame: All time points
measure: Neutralizing capacity of SARS-CoV-2 antibodies
timeFrame: Measurements at baseline, 21-28 days after first vaccination and 28 days, and 12 months after second vaccination.
measure: Incidence and outcome of SARS-CoV-2 infection
timeFrame: During time period of 12 months after vaccination.
Locations:
city: Utrecht
country: Netherlands
facility: UMC utrecht
Study officials:
affiliation: UMC Utrecht
name: Louis J Bont, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Streng BMM, Bont M, Delemarre EM, Binnendijk RS, Smit G, den Hartog G, Coppus AMW, de Vries E, Weijerman ME, Lamberts R, de Graaf G, van der Klis FR, Vidarsson G, Rave N, Bont LJ, Wildenbeest JG. Decreased Antibody Response After Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination in Patients With Down Syndrome. J Infect Dis. 2022 Sep 4;226(4):673-677. doi: 10.1093/infdis/jiac235.