Clinical trial NCT03861130: Genetic Determinants of Kawasaki Disease
Official title: Genetic Determinants of Kawasaki Disease for Susceptibility and Outcome
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Kawasaki Disease
Atypical Kawasaki Disease
Keywords: Kawasaki Disease
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: Guy's and St Thomas' NHS Foundation Trust
name: University Hospitals Bristol and Weston NHS Foundation Trust
name: Great Ormond Street Hospital for Children NHS Foundation Trust
name: UK Kawasaki Support Group
name: Imperial College Healthcare NHS Trust
name: University Hospitals of North Midlands NHS Trust
name: Burton Hospitals NHS Foundation Trust
name: York Teaching Hospitals NHS Foundation Trust
name: Shrewsbury and Telford Hospitals NHS Trust
name: East Suffolk and North Essex NHS Foundation Trust
name: New Cross Hospital
name: Darlington Memorial Hospital
name: Torbay Hospital
name: Peterborough City Hospital
name: University Hospitals Coventry and Warwickshire NHS Trust
name: University Hospital of North Tees
name: Cambridge University Hospitals NHS Foundation Trust
name: Royal Cornwall Hospitals Trust
name: Birmingham Children's Hospital
name: University Hospital Birmingham NHS Foundation Trust
name: Wye Valley NHS Trust
name: South Tees Hospitals NHS Foundation Trust
name: Leeds General Infirmary
name: Bradford Royal Infirmary
name: University Hospitals of Morecambe Bay NHS Trust
name: Calderdale and Huddersfield NHS Foundation Trust
name: St. Richard's Hospital
name: Pinderfields General Hospital
name: Worthing Hospital
name: Airedale General Hospital
name: Sheffield Children's NHS Foundation Trust
name: Northwick Park Hospital
name: West Middlesex Hospital
name: Royal Albert Edward Infirmary
name: Macclesfield District General Hospital
name: Royal Oldham Hospital
name: Stepping Hill Hospital
name: North Manchester General Hospital
name: Royal Bolton Hospital NHS Foundation Trust
name: Kingston Hospital NHS Trust
name: Tameside Hospital NHS Foundation Trust
name: East Surrey Hospital
name: St. George's Hospital, London
name: Royal Alexandra Children's Hospital
First posted: 2019-03-04
Enrollment: 1379
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: PROBABILITY_SAMPLE
Study population: Children under the care of consultant in hospital for Kawasaki disease, families who are members of the UK Kawasaki Support Group

Brief summary: Kawasaki disease (KD) is an acute self-limited vasculitis of infancy and early childhood. Most patients recover without sequelae although the inflammatory process causes permanent damage to the coronary arteries in 20-25% of untreated children. An infectious aetiology is suspected, but the causative agent has not been identified. The investigators aim to identify the genes underlying both susceptibility to Kawasaki disease, and the development of coronary artery aneurysms.

Detailed description: The problem to be addressed;

Kawasaki disease is now the most common cause of acquired heart disease in children in Japan and North America. Kawasaki disease arises when genetically predisposed children encounter an as yet unidentified infectious agent which may cause only mild illness or no illness at all in children without the genetic predisposition. Other children may suffer permanent damage to the coronary arteries. Identification of the genes involved will help to improve understanding of the disease, and the development of better treatments.

Objective

The investigators aim to identify the genes underlying both susceptibility to Kawasaki disease, and the development of coronary artery aneurysms.

Design

The study will recruit nuclear families (affected child and their biological parents) through participating NHS hospitals or through the records of the UK Kawasaki Support Group.

Study size

400 affected children and both biological parents (i.e. 1200 participants)

Procedures

Informed consent using age appropriate patient/parent/guardian information sheets will be taken from parents (or from children aged 16 and over), assent will be taken from the child under the age of 16 (if appropriate). Children recruited during the acute illness; routine clinical and laboratory data and research samples (blood, urine, throat swab). Children recruited retrospectively; study questionnaire (completed by parents), saliva samples.Saliva samples from parents

Eligibility criteria: Inclusion Criteria:

* Affected children will be recruited if the treating clinician has made a diagnosis of possible Kawasaki disease (even if they do not fulfil the criteria below for Kawasaki disease).

The current standard diagnostic criteria for KD (Circulation 2001 103 335-336 doi: 10.1161/01.CIR 103.2.335) are:

The presence of fever for at least five days plus four of the following criteria:

1. Changes in the peripheral extremities Acute: erythema and oedema of hands and feet Convalescent: membranous desquamation of fingertips
2. Polymorphous exanthema
3. Bilateral painless bulbar conjunctival injection without exudate
4. Changes in lips and oral cavity: erythema and cracking of lips, strawberry tongue, diffuse injection of oral and pharyngeal mucosae
5. Cervical lymphadenopathy (\>1.5cm diameter), usually unilateral Patients meeting not all of these criteria may meet the criteria for atypical Kawasaki disease, ie. if they have fever and two or three of the above criteria and elevation of CRP or echocardiographic evidence of coronary artery dilatation.

Parents of affected child must be biological parents.

Exclusion Criteria:

* children who do not have a diagnosis of possible Kawasaki disease

Primary outcomes:
measure: Susceptibility of coronary artery aneurysms for Kawasaki patients
timeFrame: end date; 30 December 2022
Secondary outcomes:
measure: Disease severity for Kawasaki patients
timeFrame: end date; 30 December 2022
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Imperial College London
Study officials:
affiliation: Imperial College London
name: Professor M Levin
role: STUDY_CHAIR
References: