Clinical trial NCT02429531: Polysaccharide Antibody Response Study
Official title: The Polysaccharide Antibody Response Study: Typhim Vi Response and Allohemagglutinins Versus Pneumovax 23 Vaccine Response in the Diagnosis of Specific Polysaccharide Antibody Deficiency
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Specific Polysaccharide Antibody Deficiency
Keywords: Pneumovax 23
Typhim Vi
allohemagglutinins
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
Collaborators: name: KU Leuven
First posted: 2015-04-29
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: Specific polysaccharide antibody deficiency (SPAD) is a primary immunodeficiency characterized by a deficient antibody production to capsular polysaccharides with normal total immunoglobulin levels. Patients suffer from recurrent ear-nose and throat infections and lung infections. SPAD can also occur as part of a primary immunodeficiency affecting other components of the immune system. Diagnosis of SPAD is hampered by difficulties with the interpretation of the Pneumovax 23 antibody response. The purpose of this study is to assess the diagnostic value of the Typhim Vi antibody response and allohemagglutinin titers as an alternative to the Pneumovax 23 response to detect polysaccharide specific antibody deficiency.

Detailed description: Healthy controls (n = 100) and patients with suspected SPAD (n = 100) will be immunized with both Pneumovax 23 and Typhim Vi (age 18 months - 55 years). Analyses of anti-pneumococcal polysaccharide antibodies and anti-Vi antibodies are performed before and 3-4 weeks after vaccination. Also bloodgroup and anti-A/anti-B are assessed. Relevant clinical information (ENT infections, lung infections, bronchiectasis, invasive infections) is obtained from the patient file and history and is noted in a Case Report Form.

The diagnostic performance of Typhim Vi response and allohemagglutinins will be analyzed by calculating sensitivity, specificity, predictive values, likelihood ratios and Receiver Operating Characteristic curves for Typhim Vi and allohemagglutinins using pneumococcal antibody response as the reference standard. The association between low Typhim Vi response or low allohemagglutinins and clinical signs of polysaccharide antibody deficiency will be studied by multiple logistic regression.

Eligibility criteria: Inclusion Criteria:

* Assessment of polysaccharide antibody response is indicated for the clinical care of the patient (not for healthy volunteers)
* Informed consent given

Exclusion Criteria:

* History of serious adverse reaction to a vaccine
* Vaccination with Typhim Vi or Pneumovax 23 in 5 years prior to the study
* (Potential) pregnancy

Primary outcomes:
measure: Typhim Vi response specific anti-Vi IgG as measured by ELISA
timeFrame: 3-4 weeks
measure: Pneumovax 23 response specific pneumococcal polysaccharide IgG as measured by ELISA
timeFrame: 3-4 weeks
Secondary outcomes:
measure: allohemaglutinin titer as measured by column agglutination
timeFrame: 1 day
measure: ENT infections (number of ENT infections obtained by history and medical file)
timeFrame: 12 months before inclusion untill inclusion
measure: pneumonia (number of lung infections, confirmed on chest radiography, obtained by history and medical file)
timeFrame: 5 years before inclusion untill inclusion
measure: invasive infections (number and infection site of invasive infections obtained by history and medical file)
timeFrame: 5 years before inclusion untill inclusion
measure: bronchiectasis (presence or absence of bronchiectasis (diagnosed by high resolution CT) obtained by history and medical file)
timeFrame: 5 years before inclusion untill inclusion
measure: adverse effects
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: UZ Leuven
Study officials:
affiliation: UZ Leuven
name: Isabelle Meyts, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Schaballie H, Vermeulen F, Verbinnen B, Frans G, Vermeulen E, Proesmans M, De Vreese K, Emonds MP, De Boeck K, Moens L, Picard C, Bossuyt X, Meyts I. Value of allohaemagglutinins in the diagnosis of a polysaccharide antibody deficiency. Clin Exp Immunol. 2015 May;180(2):271-9. doi: 10.1111/cei.12571.