MEASLES DISEASEMISIA-kNCT06923631
Unravelling the Measles Paradox in Children
An observational study of MEASLES DISEASE, run by Erasmus Medical Center at 1 site in Netherlands.
Trial summary
Measles is caused by measles virus (MeV). The disease is associated with lymphopenia and immune suppression, which is an important cause of measles-associated morbidity and mortality. Measles-induced immune suppression can last several years, whereas measles lymphopenia is usually resolved within two weeks. Read more about this study
- Who is it for?
- Ages 4 to 17 yearsHealthy volunteers can take part
- Conditions the study is for
- MEASLES DISEASE
- How many people
- 100 participants
- Where
- 1 siteNetherlands
- Study dates
- 3 Jan 2026to 1 Apr 2029
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 4 to 17 years
- All sexes
- Healthy volunteers accepted
- Child
Study population: Children in group A will be from 4 up to and including 17 years of age and include children who are not protected against measles. Families willing to participate will self-identify them to the researchers, with the help of schools, Municipal Health Services and regional general practitioners. Children in group B will be from 4 up to and including 17 years of age and have received one or two MMR vaccinations, depending on their age. The children will be recruited from the same geographical regions with low vaccine coverage as the children in group A, for example classmates.
Who may be able to join
- Group A
- Aged 4 - 17 years old
- Susceptible to measles
- No pre-existing immunity against measles (vaccination or earlier infection)
- Group B
- Aged 4 - 17 years old
- Protected against measles due to vaccination or earlier infection
Who cannot join
- A potential subject who meets any of the following criteria will be excluded from participation in this study:
- Diagnosed chronic disease that lasted over 3 months
- Immune suppression (due to medication or underlying disease)
- Group A; Detectable MeV-antibodies in the T1 blood sample
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Unravelling the Measles Paradox in Children: a Disease Associated With Both Immune Suppression and Immune Activation
Measles is caused by measles virus (MeV). The disease is associated with lymphopenia and immune suppression, which is an important cause of measles-associated morbidity and mortality. Measles-induced immune suppression can last several years, whereas measles lymphopenia is usually resolved within two weeks. At the same time, measles induces lifelong immunity. This apparent contradiction, known as the 'measles paradox', was partially solved when investigators demonstrated that MeV infects and depletes pre-existing memory cells, thereby causing 'immune amnesia'. This model is supported by observations in animal models and clinical studies, but several questions remain to be addressed, like the duration of measles-induced amnesia and changes in the immune repertoire after measles. to address the immunological questions regarding MeV infection.
Read the detailed description
Measles is caused by measles virus (MeV). The disease is associated with lymphopenia and immune suppression, which is an important cause of measles-associated morbidity and mortality. Measles-induced immune suppression can last several years, whereas measles lymphopenia is usually resolved within two weeks. At the same time, measles induces lifelong immunity. This apparent contradiction, known as the 'measles paradox', was partially solved when investigators demonstrated that MeV infects and depletes pre-existing memory cells, thereby causing 'immune amnesia'. This model is supported by observations in animal models and clinical studies, but several questions remain to be addressed, like the duration of measles-induced amnesia and changes in the immune repertoire after measles. Recently, investigators have acquired permission to address these remaining questions in 18-25 years old adults (MEC-2024-0230). However, investigators have reservations about the feasibility of including enough participants between 18 and 25 years old that have not been vaccinated against or infected with MeV; it is possible that investigators will not reach sufficient inclusions to address the immunological questions regarding MeV infection in that protocol. Therefore, investigators propose to additionally study these questions in children in the age of 4 up to and including 17.
- Conditions
- MEASLES DISEASE
- Keywords
- measles, immune response
- Medical subject headings
- Measles
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Group A (max 50 inclusions) | Unprotected children with at least one sibling diagnosed with measles | |
| Group B (max 50 inclusions) | Age matched children with detectable immunity to MeV |
What is being measured
The primary outcome is the main question the study is designed to answer.
Compare measles-induced loss of pathogen-specific antibodies
The investigators will measure changes in the immune repertoire using longitudinal samples obtained from children who are infected with MeV. To this end, they will measure pathogen-specific antibody responses (titers) pre- and post-measles and compare these to determine whether measles led to a loss of pathogen-specific antibodies.
Measured: 36 months
Compare measles-induced loss of pathogen-specific T-cells
The investigators will measure changes in the immune repertoire using longitudinal samples obtained from children who are infected with MeV. To this end, they will measure pathogen-specific T-cell responses (frequencies) pre- and post-measles and compare these to determine whether measles led to a loss of pathogen-specific T-cells.
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2025
- Study start3 Jan 2026 (estimated)
- Primary completion1 Apr 2029 (estimated)
- Study completion1 Apr 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (25)Papers the sponsor has linked to this study.
- Other trials for MEASLES DISEASEStudies of the same condition, open and under way.
- More trials run by Erasmus 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
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Erasmus Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Corine Geurts van Kessel, Erasmus Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06923631
- Sponsor's protocol ID
- NL-009458
- Acronym
- MISIA-k
- Status last verified
- Nov 2025
- First submitted
- 27 Mar 2025
- Last updated
- 26 Nov 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
van Velzen E, de Coster E, van Binnendijk R, Hahne S. Measles outbreak in an anthroposophic community in The Hague, The Netherlands, June-July 2008. Euro Surveill. 2008 Jul 31;13(31):18945. No abstract available.
PubMed 18761905Mollema L, Harmsen IA, Broekhuizen E, Clijnk R, De Melker H, Paulussen T, Kok G, Ruiter R, Das E. Disease detection or public opinion reflection? Content analysis of tweets, other social media, and online newspapers during the measles outbreak in The Netherlands in 2013. J Med Internet Res. 2015 May 26;17(5):e128. doi: 10.2196/jmir.3863.
PubMed 26013683Laksono BM, de Vries RD, Verburgh RJ, Visser EG, de Jong A, Fraaij PLA, Ruijs WLM, Nieuwenhuijse DF, van den Ham HJ, Koopmans MPG, van Zelm MC, Osterhaus ADME, de Swart RL. Studies into the mechanism of measles-associated immune suppression during a measles outbreak in the Netherlands. Nat Commun. 2018 Nov 23;9(1):4944. doi: 10.1038/s41467-018-07515-0.
PubMed 30470742Knol M, Urbanus A, Swart E, Mollema L, Ruijs W, van Binnendijk R, Te Wierik M, de Melker H, Timen A, Hahne S. Large ongoing measles outbreak in a religious community in the Netherlands since May 2013. Euro Surveill. 2013 Sep 5;18(36):pii=20580. doi: 10.2807/1560-7917.es2013.18.36.20580.
PubMed 24079377Van Den Hof S, Smit C, Van Steenbergen JE, De Melker HE. Hospitalizations during a measles epidemic in the Netherlands, 1999 to 2000. Pediatr Infect Dis J. 2002 Dec;21(12):1146-50. doi: 10.1097/00006454-200212000-00012.
PubMed 12488666Mina MJ, Kula T, Leng Y, Li M, de Vries RD, Knip M, Siljander H, Rewers M, Choy DF, Wilson MS, Larman HB, Nelson AN, Griffin DE, de Swart RL, Elledge SJ. Measles virus infection diminishes preexisting antibodies that offer protection from other pathogens. Science. 2019 Nov 1;366(6465):599-606. doi: 10.1126/science.aay6485.
PubMed 31672891Rennick LJ, de Vries RD, Carsillo TJ, Lemon K, van Amerongen G, Ludlow M, Nguyen DT, Yuksel S, Verburgh RJ, Haddock P, McQuaid S, Duprex WP, de Swart RL. Live-attenuated measles virus vaccine targets dendritic cells and macrophages in muscle of nonhuman primates. J Virol. 2015 Feb;89(4):2192-200. doi: 10.1128/JVI.02924-14. Epub 2014 Dec 3.
PubMed 25473055de Vries RD, Lemon K, Ludlow M, McQuaid S, Yuksel S, van Amerongen G, Rennick LJ, Rima BK, Osterhaus AD, de Swart RL, Duprex WP. In vivo tropism of attenuated and pathogenic measles virus expressing green fluorescent protein in macaques. J Virol. 2010 May;84(9):4714-24. doi: 10.1128/JVI.02633-09. Epub 2010 Feb 24.
PubMed 20181691Aaby P, Bukh J, Lisse IM, Smits AJ. Measles vaccination and reduction in child mortality: a community study from Guinea-Bissau. J Infect. 1984 Jan;8(1):13-21. doi: 10.1016/s0163-4453(84)93192-x.
PubMed 6699411Sato R, Haraguchi M. Effect of measles prevalence and vaccination coverage on other disease burden: evidence of measles immune amnesia in 46 African countries. Hum Vaccin Immunother. 2021 Dec 2;17(12):5361-5366. doi: 10.1080/21645515.2021.2013078. Epub 2021 Dec 29.
PubMed 34965183Petrova VN, Sawatsky B, Han AX, Laksono BM, Walz L, Parker E, Pieper K, Anderson CA, de Vries RD, Lanzavecchia A, Kellam P, von Messling V, de Swart RL, Russell CA. Incomplete genetic reconstitution of B cell pools contributes to prolonged immunosuppression after measles. Sci Immunol. 2019 Nov 1;4(41):eaay6125. doi: 10.1126/sciimmunol.aay6125.
PubMed 31672862Cox RM, Wolf JD, Lieberman NA, Lieber CM, Kang HJ, Sticher ZM, Yoon JJ, Andrews MK, Govindarajan M, Krueger RE, Sobolik EB, Natchus MG, Gewirtz AT, deSwart RL, Kolykhalov AA, Hekmatyar K, Sakamoto K, Greninger AL, Plemper RK. Therapeutic mitigation of measles-like immune amnesia and exacerbated disease after prior respiratory virus infections in ferrets. Nat Commun. 2024 Feb 8;15(1):1189. doi: 10.1038/s41467-024-45418-5.
PubMed 38331906Laksono BM, Roelofs D, Comvalius AD, Schmitz KS, Rijsbergen LC, Geers D, Nambulli S, van Run P, Duprex WP, van den Brand JMA, de Vries RD, de Swart RL. Infection of ferrets with wild type-based recombinant canine distemper virus overwhelms the immune system and causes fatal systemic disease. mSphere. 2023 Aug 24;8(4):e0008223. doi: 10.1128/msphere.00082-23. Epub 2023 Jun 28.
PubMed 37377421Ward BJ, Johnson RT, Vaisberg A, Jauregui E, Griffin DE. Cytokine production in vitro and the lymphoproliferative defect of natural measles virus infection. Clin Immunol Immunopathol. 1991 Nov;61(2 Pt 1):236-48. doi: 10.1016/s0090-1229(05)80027-3.
PubMed 1914259Hirsch RL, Griffin DE, Johnson RT, Cooper SJ, Lindo de Soriano I, Roedenbeck S, Vaisberg A. Cellular immune responses during complicated and uncomplicated measles virus infections of man. Clin Immunol Immunopathol. 1984 Apr;31(1):1-12. doi: 10.1016/0090-1229(84)90184-3.
PubMed 6230187
Study at a glance
From the registry record, last updated by the sponsor on 26 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Unravelling the Measles Paradox in Children: a Disease Associated With Both Immune Suppression and Immune Activation
- ClinicalTrials.gov ID
- NCT06923631
- Acronym / sponsor ID
- MISIA-k / NL-009458
- Conditions
- MEASLES DISEASE
- Keywords
- measles, immune response
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Erasmus Medical CenterUniversity, hospital or other
- Study start
- 3 Jan 2026 (estimated)
- Primary completion
- 1 Apr 2029 (estimated)
- Study completion
- 1 Apr 2029 (estimated)
- First posted
- 11 Apr 2025 (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.
Measles is caused by measles virus (MeV). The disease is associated with lymphopenia and immune suppression, which is an important cause of measles-associated morbidity and mortality. Measles-induced immune suppression can last several years, whereas measles lymphopenia is usually resolved within two weeks. At the same time, measles induces lifelong immunity. This apparent contradiction, known as the 'measles paradox', was partially solved when investigators demonstrated that MeV infects and depletes pre-existing memory cells, thereby causing 'immune amnesia'. This model is supported by observations in animal models and clinical studies, but several questions remain to be addressed, like the duration of measles-induced amnesia and changes in the immune repertoire after measles. to address the immunological questions regarding MeV infection.
Detailed description
Measles is caused by measles virus (MeV). The disease is associated with lymphopenia and immune suppression, which is an important cause of measles-associated morbidity and mortality. Measles-induced immune suppression can last several years, whereas measles lymphopenia is usually resolved within two weeks. At the same time, measles induces lifelong immunity. This apparent contradiction, known as the 'measles paradox', was partially solved when investigators demonstrated that MeV infects and depletes pre-existing memory cells, thereby causing 'immune amnesia'. This model is supported by observations in animal models and clinical studies, but several questions remain to be addressed, like the duration of measles-induced amnesia and changes in the immune repertoire after measles. Recently, investigators have acquired permission to address these remaining questions in 18-25 years old adults (MEC-2024-0230). However, investigators have reservations about the feasibility of including enough participants between 18 and 25 years old that have not been vaccinated against or infected with MeV; it is possible that investigators will not reach sufficient inclusions to address the immunological questions regarding MeV infection in that protocol. Therefore, investigators propose to additionally study these questions in children in the age of 4 up to and including 17.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A (max 50 inclusions) | – | –Unprotected children with at least one sibling diagnosed with measles |
| Group B (max 50 inclusions) | – | –Age matched children with detectable immunity to MeV |
Who may qualify
- Ages
- 4 to 17 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- Study population
- Children in group A will be from 4 up to and including 17 years of age and include children who are not protected against measles. Families willing to participate will self-identify them to the researchers, with the help of schools, Municipal Health Services and regional general practitioners. Children in group B will be from 4 up to and including 17 years of age and have received one or two MMR vaccinations, depending on their age. The children will be recruited from the same geographical regions with low vaccine coverage as the children in group A, for example classmates.
Key inclusion criteria (7 listed)
- Group A
- Aged 4 - 17 years old
- Susceptible to measles
- No pre-existing immunity against measles (vaccination or earlier infection)
- Group B
Key exclusion criteria (4 listed)
- A potential subject who meets any of the following criteria will be excluded from participation in this study:
- Diagnosed chronic disease that lasted over 3 months
- Immune suppression (due to medication or underlying disease)
- Group A; Detectable MeV-antibodies in the T1 blood sample
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Compare measles-induced loss of pathogen-specific antibodies
Time frame: 36 months
The investigators will measure changes in the immune repertoire using longitudinal samples obtained from children who are infected with MeV. To this end, they will measure pathogen-specific antibody responses (titers) pre- and post-measles and compare these to determine whether measles led to a loss of pathogen-specific antibodies.
Compare measles-induced loss of pathogen-specific T-cells
Time frame: 36 months
The investigators will measure changes in the immune repertoire using longitudinal samples obtained from children who are infected with MeV. To this end, they will measure pathogen-specific T-cell responses (frequencies) pre- and post-measles and compare these to determine whether measles led to a loss of pathogen-specific T-cells.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Nov 2025.
- Background: PubMed 18761905van Velzen E, de Coster E, van Binnendijk R, Hahne S. Measles outbreak in an anthroposophic community in The Hague, The Netherlands, June-July 2008. Euro Surveill. 2008 Jul 31;13(31):18945. No abstract available.
- Background: PubMed 26013683Mollema L, Harmsen IA, Broekhuizen E, Clijnk R, De Melker H, Paulussen T, Kok G, Ruiter R, Das E. Disease detection or public opinion reflection? Content analysis of tweets, other social media, and online newspapers during the measles outbreak in The Netherlands in 2013. J Med Internet Res. 2015 May 26;17(5):e128. doi: 10.2196/jmir.3863.
- Background: PubMed 30470742Laksono BM, de Vries RD, Verburgh RJ, Visser EG, de Jong A, Fraaij PLA, Ruijs WLM, Nieuwenhuijse DF, van den Ham HJ, Koopmans MPG, van Zelm MC, Osterhaus ADME, de Swart RL. Studies into the mechanism of measles-associated immune suppression during a measles outbreak in the Netherlands. Nat Commun. 2018 Nov 23;9(1):4944. doi: 10.1038/s41467-018-07515-0.
- Background: PubMed 24079377Knol M, Urbanus A, Swart E, Mollema L, Ruijs W, van Binnendijk R, Te Wierik M, de Melker H, Timen A, Hahne S. Large ongoing measles outbreak in a religious community in the Netherlands since May 2013. Euro Surveill. 2013 Sep 5;18(36):pii=20580. doi: 10.2807/1560-7917.es2013.18.36.20580.
- Background: PubMed 12488666Van Den Hof S, Smit C, Van Steenbergen JE, De Melker HE. Hospitalizations during a measles epidemic in the Netherlands, 1999 to 2000. Pediatr Infect Dis J. 2002 Dec;21(12):1146-50. doi: 10.1097/00006454-200212000-00012.
- Background: PubMed 31672891Mina MJ, Kula T, Leng Y, Li M, de Vries RD, Knip M, Siljander H, Rewers M, Choy DF, Wilson MS, Larman HB, Nelson AN, Griffin DE, de Swart RL, Elledge SJ. Measles virus infection diminishes preexisting antibodies that offer protection from other pathogens. Science. 2019 Nov 1;366(6465):599-606. doi: 10.1126/science.aay6485.
- Background: PubMed 25473055Rennick LJ, de Vries RD, Carsillo TJ, Lemon K, van Amerongen G, Ludlow M, Nguyen DT, Yuksel S, Verburgh RJ, Haddock P, McQuaid S, Duprex WP, de Swart RL. Live-attenuated measles virus vaccine targets dendritic cells and macrophages in muscle of nonhuman primates. J Virol. 2015 Feb;89(4):2192-200. doi: 10.1128/JVI.02924-14. Epub 2014 Dec 3.
- Background: PubMed 20181691de Vries RD, Lemon K, Ludlow M, McQuaid S, Yuksel S, van Amerongen G, Rennick LJ, Rima BK, Osterhaus AD, de Swart RL, Duprex WP. In vivo tropism of attenuated and pathogenic measles virus expressing green fluorescent protein in macaques. J Virol. 2010 May;84(9):4714-24. doi: 10.1128/JVI.02633-09. Epub 2010 Feb 24.
- Background: PubMed 6699411Aaby P, Bukh J, Lisse IM, Smits AJ. Measles vaccination and reduction in child mortality: a community study from Guinea-Bissau. J Infect. 1984 Jan;8(1):13-21. doi: 10.1016/s0163-4453(84)93192-x.
- Background: PubMed 34965183Sato R, Haraguchi M. Effect of measles prevalence and vaccination coverage on other disease burden: evidence of measles immune amnesia in 46 African countries. Hum Vaccin Immunother. 2021 Dec 2;17(12):5361-5366. doi: 10.1080/21645515.2021.2013078. Epub 2021 Dec 29.
- Background: PubMed 31672862Petrova VN, Sawatsky B, Han AX, Laksono BM, Walz L, Parker E, Pieper K, Anderson CA, de Vries RD, Lanzavecchia A, Kellam P, von Messling V, de Swart RL, Russell CA. Incomplete genetic reconstitution of B cell pools contributes to prolonged immunosuppression after measles. Sci Immunol. 2019 Nov 1;4(41):eaay6125. doi: 10.1126/sciimmunol.aay6125.
- Background: PubMed 38331906Cox RM, Wolf JD, Lieberman NA, Lieber CM, Kang HJ, Sticher ZM, Yoon JJ, Andrews MK, Govindarajan M, Krueger RE, Sobolik EB, Natchus MG, Gewirtz AT, deSwart RL, Kolykhalov AA, Hekmatyar K, Sakamoto K, Greninger AL, Plemper RK. Therapeutic mitigation of measles-like immune amnesia and exacerbated disease after prior respiratory virus infections in ferrets. Nat Commun. 2024 Feb 8;15(1):1189. doi: 10.1038/s41467-024-45418-5.
- WHO measles factsheetLink provided by the sponsor.
- A 30-fold rise of measles cases in 2023 in the WHO European Region warrants urgent actionLink provided by the sponsor.
- Threat assessment brief: Measles on the rise in the EU/EEA - Considerations for public health responseLink provided by the sponsor.
- 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.
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 MEASLES DISEASE, run by Erasmus 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 7 inclusion and 4 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: opening soon, as of the sponsor's last update on 26 Nov 2025. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Dr C.H. Geurts van Kessel (+31643271384, c.geurtsvankessel@erasmusmc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Compare measles-induced loss of pathogen-specific antibodies (time frame: 36 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06923631, which also lists 25 linked publications.
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 26 Nov 2025.