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Susceptibility to Infections, Tumor Risk and Liver Disease in Patients With Ataxia Telangiectasia

Not Applicable
Conditions
Ataxia Telangiectasia
Interventions
Diagnostic Test: bioelectrical impedance analysis
Diagnostic Test: blood draw
Diagnostic Test: transient elastography (FibroScan)
Diagnostic Test: ataxia score
Diagnostic Test: Five-Times-Sit-to-Stand Test
Registration Number
NCT03357978
Lead Sponsor
Johann Wolfgang Goethe University Hospital
Brief Summary

Ataxia telangiectasia (A-T) is a rare devastating human recessive disorder characterized by progressive cerebellar ataxia, immunodeficiency, chromosomal instability and cancer susceptibility. The immunodeficiency is expressed by recurring infections. It's characterised by decreased lymphocytes data as well as lack of immunglobulin A, immunglobulin G subclasses and specific antibodies against pneumococcus. Aim of the present clinical trial is to investigate frequency-, intensity- and duration of the infections as well as changes oft immune status, dimension of liver disease and tumor risk in patients with A-T, with and without immunoglobulin G substitution therapy. Transient elastography (FibroScan) will be performed in order to measure liver stiffness as an indication of fatty liver and liver fibrosis. A bioelectrical impedance analysis (BIA) is conducted to investigate the exact body composition. Ataxia Score is determined to define neurological problems. Every subject receives a diary to compile symptoms of infection.

Detailed Description

Ataxia teleangiectasia (A-T) is a rare devastating human recessive disorder characterized by progressive cerebellar ataxia, immunodeficiency, chromosomal instability and cancer susceptibility. The immunodeficiency is expressed by recurring infections. It's characterised by decreased lymphocytes data as well as lack of immunglobulin A, immunglobulin G subclasses and specific antibodies against pneumococcus as shown in many trials. Additionally the patients suffer from a fatty liver with increased transaminases and have the risk for a cirrhosis of the liver and a hepatocellular carcinoma. It's known that the dimension of the liver disease affects susceptibility to infection. Nevertheless there are only a few studies treating this problem.

Despite the proof of the immunodeficiency polyvalent immunoglobulins (IgG) are not given regularly. Own observations show that in spite of the treatment with immunoglobulins the progression of a chronic destructive lung disease with development of bronchiectasis hardly can prohibited.

Up to now it isn't cleared if a substitution therapy with immunoglobulins reduces the susceptibility to infection. Therefore the aim oft the present clinical trial ist to explore frequency-, intensity, and duration oft the infections as well as changes oft the immune status, measure of liver disease and tumor risk in patients with A-T, with and without immunoglobulin therapy. The study includes five visits, which are performed in all A-T patients. Visit 1, 3, 5 are realized in the context of annual follow ups:

* To evaluate weight and length of all subjects

* To analyze the exact structure of single body compartments such as the lean mass, the water compartment or the fat compartment using bioelectrical impedance analysis

* To define the neurological status by ataxia score

* To get a detailed immune status, vaccination status and liver values as well as special tumor markers in blood

* To check the lung function using spirometry

* To measure liver stiffness using transient elastography (FibroScan)

* To compile any symptoms of infection by diary

* To investigate the ataxia status and physical condition by means of the Five-Times-Sit-to-Stand Test

Visit 2 and 4 are additionally conducted as study visits:

* To get a detailed immune status in blood

* To check the lung function using spirometry

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
30
Inclusion Criteria
  • aim group: genetically and/or clinically diagnosed A-T
  • age 2-45 years
  • written informed consent
Exclusion Criteria
  • age < 2 or > 45 years
  • other diseases with influence on the immune system (i.e. diabetes mellitus, malignoma, dialysis-dependent renal failure)

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
A-T patientsbioelectrical impedance analysisA-T patients aged 2 to 45 years with and without immunoglobulin G Substitution * bioelectrical impedance Analysis * blood draw * transient elastography (FibroScan) * ataxia score * Five-Times-Sit-to-Stand Test
A-T patientsFive-Times-Sit-to-Stand TestA-T patients aged 2 to 45 years with and without immunoglobulin G Substitution * bioelectrical impedance Analysis * blood draw * transient elastography (FibroScan) * ataxia score * Five-Times-Sit-to-Stand Test
A-T patientsataxia scoreA-T patients aged 2 to 45 years with and without immunoglobulin G Substitution * bioelectrical impedance Analysis * blood draw * transient elastography (FibroScan) * ataxia score * Five-Times-Sit-to-Stand Test
A-T patientsblood drawA-T patients aged 2 to 45 years with and without immunoglobulin G Substitution * bioelectrical impedance Analysis * blood draw * transient elastography (FibroScan) * ataxia score * Five-Times-Sit-to-Stand Test
A-T patientstransient elastography (FibroScan)A-T patients aged 2 to 45 years with and without immunoglobulin G Substitution * bioelectrical impedance Analysis * blood draw * transient elastography (FibroScan) * ataxia score * Five-Times-Sit-to-Stand Test
Primary Outcome Measures
NameTimeMethod
Infections in A-T24 months

Evaluation of frequency, severity and intensity of infections in A-T patients with and without immunoglobulin G substitution

Secondary Outcome Measures
NameTimeMethod
Liver disease24 months

Evaluation of the degree of liver disease measured by liver enzymes and structural changes by transient elastography (Fibroscan) in A-T patients

Cancer risk24 months

Evaluation of tumor markers in A-T patients

Trial Locations

Locations (1)

Children's Hospital, Allergology, Pneumology and Cystic Fibrosis, Goethe University Frankfurt

🇩🇪

Frankfurt, Hessen, Germany

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