ClinicalTrials.gov record NCT05656365

Evaluating the Genetics and Immunology of Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA) Syndrome and Other Tonsil Disorders

Record copied from ClinicalTrials.gov: Oct 10, 2026AI summaries generated: Sep 17, 2026

Evaluating the Genetics and Immunology of Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA) Syndrome and Other Tonsil Disorders

StatusRecruitingThe study is currently enrolling participants. Only the study team can say whether a particular person can join.
Study typeObservationalA study in which researchers do not assign participants to a treatment or other intervention. They observe or measure what happens, which may include study visits, tests, questionnaires or a review of medical records.
AgeUnder 1 month old to 99 years old
SexAll
LocationUnited States
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

This prospective observational study collects blood, swabs, saliva, stool and leftover surgical tissue from people with PFAPA or other tonsil disorders. It is open to people aged 1 month and older with PFAPA or other tonsil-related symptoms. Most participants provide samples once; some may have optional follow-up visits over as long as 10 years.

What it is studying. The study is collecting specimens and medical data to learn which genetic, immune, cellular, molecular, and microbial features are seen in PFAPA and other tonsil disorders. Researchers plan to identify genetic risk variants, describe immune cell types and gene expression (including single-cell analyses), and profile microbiota from tonsils, throat, nose, and stool. The study also collects information on clinical outcomes after tonsillectomy and other treatments.

What the researchers hope to learn. To collect samples and data to understand immunologic mechanisms and genetic and microbial risk factors for PFAPA and other tonsil disorders; to identify genetic risk variants; to characterize immune cell populations, gene expression (including single-cell), epigenetic features, protein expression, and microbiota; and to characterize clinical outcomes after tonsillectomy and other treatments.

What this study is about

The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.

Background: Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) is the most common periodic fever syndrome of childhood. Symptoms can include swelling of the glands in the throat, mouth ulcers, and tonsillitis. Removal of the tonsils can stop the periodic flareups. But researchers do not know how PFAPA develops. In this natural history study, researchers will collect specimens and data from people with PFAPA to see what they might have in common. Objective: To collect blood and other specimens from people with PFAPA to learn more about the illness. Eligibility: People aged 1 month or older with symptoms of PFAPA or another tonsil disorder. Design: Participants will be screened. Their medical records will be reviewed. Researchers will ask about a family history of PFAPA. The following specimens may be collected: Blood. Blood will be drawn either from a needle inserted into a vein or from a prick in the finger or heel. Mucus and cells. A stick with soft padding on the tip may be rubbed inside the nostrils or mouth. Stool. Saliva. Tissue samples may be taken if participants are having surgery to remove the tonsils or adenoids. Participants having surgery may also have a nasopharyngeal wash; salt water will be squirted into the back of the throat and then sucked back out with a syringe. Most participants will provide specimens only once. They can do this in person at the clinic; they can also have their local health providers send specimens to the researchers. Some participants may have optional follow-up visits over 10 years.

Eligibility

The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.

Inclusion criteria

  • Participants must meet all the following inclusion criteria to be eligible for this study:
  • Aged >=1 month. To be seen at the NIH CC, participants must be >=3 years of age.
  • Diagnosed with PFAPA or another tonsil disorder, or has symptoms consistent with these conditions, as determined by the investigator.
  • Able to provide informed consent (for ages >=18 years) or has a parent or guardian who can provide informed consent on their behalf (for ages <18 years).
  • Willing to allow specimens and data to be stored for future research.
  • Willing to allow genetic testing on their biospecimens.

Exclusion criteria

  • An individual who has any condition that, in the judgment of the investigator, may put them at undue risk or make them unsuitable for participation in the study will be excluded.

Study description and what participation involves

The study's detailed description, as published on ClinicalTrials.gov.

Show the detailed description from the registry

Study Description: The purpose of this multisite study is to collect specimens and data from patients with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome and other tonsil disorders for genetic, immunologic, cellular, molecular, and microbial research into the pathogenesis of these conditions. Specimens include blood, saliva, buccal swabs, oropharyngeal swabs, nasopharyngeal swabs, nasopharyngeal wash, and/or stool. If a participant is scheduled to undergo a clinically indicated tonsillectomy and/or adenoidectomy, then leftover clinical specimens will also be collected for research. Participants may either be seen in person at the study sites or may be seen remotely via telehealth and provide send-in samples collected locally. Primary Objective: To collect samples to understand the immunologic mechanisms and genetic and microbial risk factors for PFAPA and other tonsil disorders. Primary Endpoints:

  • Identify genetic risk variants for PFAPA and other tonsil disorders.
  • Characterize immune cell populations, gene expression (including at the single-cell level), epigenetic features, and protein expression ex vivo in blood, tissue, washes, or swabs from people with PFAPA and other tonsil disorders.
  • Characterize the tonsillar/adenoid, oral, nasal and/or stool microbiota in people with PFAPA and other tonsil disorders.
  • Characterize clinical outcomes following tonsillectomy and other clinically indicated treatments.

Secondary Objective: To understand the characteristics and function of unique cell populations in the pharyngeal lymphoid tissues (tonsils and adenoids) and how immune responses to antigens are generated in these tissues. Secondary Endpoints:

  • Study responses to antigens and infection in the mucosal lymphoid tissue and peripheral blood.
  • Characterize unique immune cell populations present in the mucosal tissue.
  • Characterize immunologic and molecular pathways in the tissue cells.
AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

Participants will be screened and have their medical records reviewed; researchers will ask about family history. They may provide one or more research samples such as blood (needle draw or finger/heel prick), saliva, stool, and nasal or oral swabs. If undergoing clinically indicated tonsillectomy or adenoidectomy, leftover tissue and optional nasopharyngeal wash may be collected. Most people provide specimens once, but some may have optional follow-up visits or remote/send-in sample collection over a period of up to 10 years.

How the study is structured. A prospective observational cohort: participants are screened and their medical records reviewed. Samples (blood, saliva, buccal/oropharyngeal/nasopharyngeal swabs or washes, stool) are collected in clinic or sent in from local providers. If a participant has clinically indicated tonsil/adenoid surgery, leftover surgical tissue may be collected. Most people give samples once; some may join optional follow-up visits up to 10 years.

Questions you could ask

These questions are suggestions for a conversation with the study team or your own clinician, not advice.

  • The registry lists this study under Periodic Fever, Aphthous Stomatitis, Pharyngitis, And Cervical Adenitis (Pfapa); Obstructive Sleep Apnea; Tonsillitis; Tonsil Disorder; Sleep Disordered Breathing. Does it apply to my diagnosis?
  • This is an observational study, so the study itself gives no treatment. What would taking part involve for me, and would it change my usual care?
  • The listed sites are in United States. Is any of them reachable for me, and does the study help with travel?
  • Which of the eligibility criteria would need to be checked with tests before I could join?

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Important dates

Study start
May 23, 2023
Primary completion
Jun 30, 2037 (estimated)
Study completion
Dec 31, 2038 (estimated)
Target enrollment
1500 participants (estimated)
Last updated on registry
Apr 8, 2026
Data verified
Oct 10, 2026

Sponsor and research team

The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.

Lead sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

Central study contact

If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.

Participating sites (3)

Terms used on this page · explanations by MedicalUpdates.ai

natural history study
A study that follows how a condition changes over time without assigning an experimental treatment. It may involve study visits and tests, and is often used to plan future trials.
follow-up
The period after treatment or enrolment during which participants are observed or contacted, for example to record side effects or outcomes.
inclusion criteria
The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
informed consent
The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
biospecimens
A collection of biological samples, such as blood or tissue, stored with medical information so that researchers can study them later.
EXCLUSION CRITERIA
The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
Primary Objective
The main result the study is designed to measure and report on. Other results, called secondary outcomes, are also collected.
Endpoints
Something the study measures to judge its results, such as a symptom score, a blood test or survival. Outcomes are grouped as primary, secondary and sometimes exploratory.
Secondary Objective
An additional result the study measures alongside the primary outcome, for example quality of life or a laboratory value.

The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.

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