Susceptibility to Infections in Ataxia Telangiectasia

NCT02345135 | Completed

• 1 other identifier: INFECTION_AT2012
• Study Type: interventional
• Target: 41
• Locations: 0 countries
• Sites: N/A

Brief Summary

Death in Ataxia telangiectasia (A-T) is usually due to cancer or chronic lung failure around 20 years of age. Despite low lymphocyte counts (CD3, CD4, CD8 and CD19), IgA and IgG subclass deficiency opportunistic and acute severe respiratory infections are rare. The prevailing wisdom is that an immunoglobulin replacement therapy is not necessary in most of the patients. However no placebo controlled trials have been performed so far. The aim of this trial was to investigate the prevalence of mild and severe respiratory infections and / or chronic cough in classical A-T patients compared to healthy controls.

Conditions

Ataxia Telangiectasia; Infections; Immunodeficiency; Lung Disease

Outcome Measures

Primary Outcomes (1)

• Number of days with a symptom score > 3 compared to healthy subjects matched for age.

  24 months

Secondary Outcomes (4)

• Number of days of absence in kindergarten, school or at work

  24 months

• Number of cold periods

  24 months

• Number of antibiotic therapies

  24 months

• Number of severe infections

  24 months

Study Arms (2)

Ataxia Telangiectasia

ACTIVE COMPARATOR

All A-T patients presented for 3 study visits. In all visits patients had a clinical examination, a blood collection and a lung function measurement. Furthermore symptom diaries were distributed and collected on these visits.

Procedure: Blood collection; Procedure: Lung function measurement; Behavioral: Symptom diary

Healthy Control

ACTIVE COMPARATOR

All healthy controls presented for 3 study visits. In all visits patients had a clinical examination and a lung function measurement. Furthermore symptom diaries were distributed and collected on these visits.

Procedure: Lung function measurement; Behavioral: Symptom diary

Interventions

Blood collection PROCEDURE

In all patients with Ataxia telangiectasia blood was collected at each visit date to determine blood count, lymphocyte subpopulation count and immunoglobulin levels in serum (IgA, IgG, IgM, IgE), as well as alpha feto protein (AFP).

Ataxia Telangiectasia

Lung function measurement PROCEDURE

In all patients - Ataxia telangiectasia and healthy controls - a lung function measurement was done to determine vital capacity (VC), forced expiratory volume in 1 second (FEV1), peak expiratory flow (PEF) and Tiffenau index.

Ataxia Telangiectasia; Healthy Control

Symptom diary BEHAVIORAL

All patients - Ataxia telangiectasia and healthy controls - were requested to keep a symptom diary for the months September to March of the years 2012/2013 and 2013/2014 to determine days with symptoms as coughing during day and night, cold and fever, as well missing days at kindergarten/school/work, intake of medication (especially antibiotic treatment) and hospitalisations.

Ataxia Telangiectasia; Healthy Control

Eligibility Criteria

• Age: 2 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• A-T: clinically and/or genetically diagnosed A-T
• No IgG treatment from the point of being included into the study
• Healthy controls: healthy children or adults matched for gender and age
• age 2 - 45 years
• written informed consent

You may not qualify if:

• age \< 2 or \> 45 years
• patient has to be treated with IgG-replacement regularly
• Other diseases with influence on the immune system (e.g. diabetes mellitus, malignancy, dialysis-dependent renal failure)

Sponsors & Collaborators

• Johann Wolfgang Goethe University Hospital: lead
• CSL Behring: collaborator

Related Publications (7)

• Schroeder SA, Zielen S. Infections of the respiratory system in patients with ataxia-telangiectasia. Pediatr Pulmonol. 2014 Apr;49(4):389-99. doi: 10.1002/ppul.22817. Epub 2013 Jun 13.

  PMID: 23761391 BACKGROUND

• Schubert R, Reichenbach J, Rose M, Zielen S. Immunogenicity of the seven valent pneumococcal conjugate vaccine in patients with ataxia-telangiectasia. Pediatr Infect Dis J. 2004 Mar;23(3):269-70. doi: 10.1097/01.inf.0000115737.35353.55.

  PMID: 15014308 BACKGROUND

• McGrath-Morrow SA, Gower WA, Rothblum-Oviatt C, Brody AS, Langston C, Fan LL, Lefton-Greif MA, Crawford TO, Troche M, Sandlund JT, Auwaerter PG, Easley B, Loughlin GM, Carroll JL, Lederman HM. Evaluation and management of pulmonary disease in ataxia-telangiectasia. Pediatr Pulmonol. 2010 Sep;45(9):847-59. doi: 10.1002/ppul.21277.

  PMID: 20583220 BACKGROUND

• Schroeder SA, Swift M, Sandoval C, Langston C. Interstitial lung disease in patients with ataxia-telangiectasia. Pediatr Pulmonol. 2005 Jun;39(6):537-43. doi: 10.1002/ppul.20209.

  PMID: 15789441 BACKGROUND

• Driessen GJ, Ijspeert H, Weemaes CM, Haraldsson A, Trip M, Warris A, van der Flier M, Wulffraat N, Verhagen MM, Taylor MA, van Zelm MC, van Dongen JJ, van Deuren M, van der Burg M. Antibody deficiency in patients with ataxia telangiectasia is caused by disturbed B- and T-cell homeostasis and reduced immune repertoire diversity. J Allergy Clin Immunol. 2013 May;131(5):1367-75.e9. doi: 10.1016/j.jaci.2013.01.053. Epub 2013 Apr 6.

  PMID: 23566627 BACKGROUND

• Verhagen MM, Martin JJ, van Deuren M, Ceuterick-de Groote C, Weemaes CM, Kremer BH, Taylor MA, Willemsen MA, Lammens M. Neuropathology in classical and variant ataxia-telangiectasia. Neuropathology. 2012 Jun;32(3):234-44. doi: 10.1111/j.1440-1789.2011.01263.x. Epub 2011 Oct 24.

  PMID: 22017321 BACKGROUND

• Zielen S, Duecker RP, Woelke S, Donath H, Bakhtiar S, Buecker A, Kreyenberg H, Huenecke S, Bader P, Mahlaoui N, Ehl S, El-Helou SM, Pietrucha B, Plebani A, van der Flier M, van Aerde K, Kilic SS, Reda SM, Kostyuchenko L, McDermott E, Galal N, Pignata C, Perez JLS, Laws HJ, Niehues T, Kutukculer N, Seidel MG, Marques L, Ciznar P, Edgar JDM, Soler-Palacin P, von Bernuth H, Krueger R, Meyts I, Baumann U, Kanariou M, Grimbacher B, Hauck F, Graf D, Granado LIG, Prader S, Reisli I, Slatter M, Rodriguez-Gallego C, Arkwright PD, Bethune C, Deripapa E, Sharapova SO, Lehmberg K, Davies EG, Schuetz C, Kindle G, Schubert R. Simple Measurement of IgA Predicts Immunity and Mortality in Ataxia-Telangiectasia. J Clin Immunol. 2021 Nov;41(8):1878-1892. doi: 10.1007/s10875-021-01090-8. Epub 2021 Sep 3.

  PMID: 34477998 DERIVED

Related Links

• German AT-website

MeSH Terms

Conditions

Ataxia Telangiectasia; Infections; Immunologic Deficiency Syndromes; Lung Diseases

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Spinocerebellar Ataxias; Cerebellar Ataxia; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocutaneous Syndromes; Ataxia; Dyskinesias; Neurologic Manifestations; Telangiectasis; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Primary Immunodeficiency Diseases; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Immune System Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Stefan Zielen, Prof. Dr.

  Johann Wolfgang Goethe University, Childrens Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. med.

Study Record Dates

• First Submitted: January 19, 2015
• First Posted: January 26, 2015
• Study Start: September 1, 2012
• Primary Completion: January 31, 2016
• Study Completion: July 31, 2016
• Last Updated: November 30, 2017

Record last verified: 2017-11