NCT05145348

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
640

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started Feb 2021

Typical duration for all trials

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 3, 2021

Completed
10 months until next milestone

First Submitted

Initial submission to the registry

December 3, 2021

Completed
3 days until next milestone

First Posted

Study publicly available on registry

December 6, 2021

Completed
7 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2022

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2023

Completed
Last Updated

December 30, 2021

Status Verified

December 1, 2021

Enrollment Period

1.4 years

First QC Date

December 3, 2021

Last Update Submit

December 9, 2021

Conditions

Down SyndromeSARS-CoV-2 Vaccination

Keywords

Down SyndromeSARS-CoV-2 vaccinationImmuneresponse

Outcome Measures

Primary Outcomes (1)

  • Antibody based immune response to vaccination against COVID-19 28 days (t=3) after the second vaccination as compared to controls.

    Participants will be classified as responders or non-responders. The definition of response will be based on the latest available data from the pivotal studies and will be defined prior to data analyses and the first database lock. The percentage of responders in the DS cohort will be compared with the percentage responders in the HS cohort.

    28 days after the second vaccination

Secondary Outcomes (3)

  • Longevity of SARS-CoV-2 specific antibodies

    1 year after the second vaccination

  • SARS-CoV2 specific T cell response

    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

  • Mucosal SARS-CoV-2 specific antibodies

    Mucosal antibodies will be measured 28 days and 12 months after the second vaccination.

Other Outcomes (4)

  • Determination of fucosylation, sialylation, galactosylation and bisection of IgG in patients with a history of COVID-19.

    All time points

  • Age-specific T-cell immunophenotyping

    All time points

  • Neutralizing capacity of SARS-CoV-2 antibodies

    Measurements at baseline, 21-28 days after first vaccination and 28 days, and 12 months after second vaccination.

  • +1 more other outcomes

Study Arms (4)

Down syndrome, adults

Adults and adolescents with Down syndrome \>16 years old.

Biological: Immune response to Sars-CoV-2 vaccinations; including COVID-19 vaccin Moderna, Comirnaty (Pfizer) and Vaxzevria (AstraZeneca)

Healthy control, adults

Healthy adults and adolescents without Down syndrome \> 16 years old. Without any significant comorbidities.

Biological: Immune response to Sars-CoV-2 vaccinations; including COVID-19 vaccin Moderna, Comirnaty (Pfizer) and Vaxzevria (AstraZeneca)

Down syndrome, children

Children with Down syndrome \< 16 years old.

Biological: Immune response to Sars-CoV-2 vaccinations; including COVID-19 vaccin Moderna, Comirnaty (Pfizer) and Vaxzevria (AstraZeneca)

Healthy control, children

Healthy children without Down syndrome \< 16 years old. Without any significant comorbidities.

Biological: Immune response to Sars-CoV-2 vaccinations; including COVID-19 vaccin Moderna, Comirnaty (Pfizer) and Vaxzevria (AstraZeneca)

Interventions

Immune response to Sars-CoV-2 vaccinations; including COVID-19 vaccin Moderna, Comirnaty (Pfizer) and Vaxzevria (AstraZeneca)BIOLOGICAL

The vaccination is not part of the study, but part of the national immunization programme of the Netherlands. Blood will be drawn at 4 time points: baseline (t=1, \<2 months prior to first vaccination); t=2: 21-28 days after first vaccination and prior to second vaccination; t=3: 28 (21-42) days after second vaccination; t=4: 12 months (+/- 1 month) after second vaccination. 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.

Down syndrome, adultsDown syndrome, childrenHealthy control, adultsHealthy control, children

Eligibility Criteria

Age12 Years+
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)
Sampling MethodProbability 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.

You may qualify if:

  • 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.

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

UMC utrecht

Utrecht, 3584 CX, Netherlands

RECRUITING

Related Publications (3)

  • Streng BMM, Hensen LCM, Delemarre EM, Binnendijk RS, Smits G, den Hartog G, van der Klis FR, de Vries E, Burger JA, van Gils MJ, Coppus AMW, Weijerman ME, Lamberts R, de Graaf G, Bont LJ, Wildenbeest JG. Antibody concentration and function following SARS-CoV-2 vaccination decrease with age in adults and children with Down syndrome. Vaccine. 2026 Feb 15;73:128079. doi: 10.1016/j.vaccine.2025.128079. Epub 2025 Dec 24.

    PMID: 41447779DERIVED

  • Hensen LCM, Streng BMM, van Wijk F, Nierkens S, van Binnendijk RS, Buisman AM, Coppus AMW, Geurts van Kessel CH, de Graaf G, van der Klis FR, Lamberts R, Vidarsson G, Ruckwardt TJ, de Vries E, de Vries RD, Weijerman ME, Weinberger DM, Wildenbeest JG, Bont LJ, Delemarre EM. T-cell responses to SARS-CoV-2 vaccinations in adults with Down syndrome - a prospective cohort study. Hum Vaccin Immunother. 2025 Dec;21(1):2583416. doi: 10.1080/21645515.2025.2583416. Epub 2025 Nov 6.

    PMID: 41196011DERIVED

  • 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.

    PMID: 35748853DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Serum, Whole blood, PBMC's, mucosal nose swab

MeSH Terms

Conditions

Down Syndrome

Interventions

BNT162 VaccineChAdOx1 nCoV-19

Condition Hierarchy (Ancestors)

Intellectual DisabilityNeurobehavioral ManifestationsNeurologic ManifestationsNervous System DiseasesAbnormalities, MultipleCongenital AbnormalitiesCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesChromosome DisordersGenetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

mRNA VaccinesNucleic Acid-Based VaccinesVaccines, SyntheticRecombinant ProteinsProteinsAmino Acids, Peptides, and ProteinsVaccinesBiological ProductsComplex MixturesCOVID-19 VaccinesViral VaccinesAntigensBiological FactorsVaccines, DNA

Study Officials

  • Louis J Bont, MD, PhD

    UMC Utrecht

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Joanne G Wildenbeest, MD, PhD

CONTACT

0031887563776J.G.Wildenbeest-2@umcutrecht.nl

Bianca MM Streng, MD

CONTACT

+31650177982b.m.m.streng-3@umcutrecht.nl

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Clinical Professor, Principal investigator

Study Record Dates

First Submitted

December 3, 2021

First Posted

December 6, 2021

Study Start

February 3, 2021

Primary Completion

June 30, 2022

Study Completion

June 30, 2023

Last Updated

December 30, 2021

Record last verified: 2021-12

Locations

NL(1)