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

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ClinicalTrials.gov Identifier: NCT03357978
Recruitment Status : Recruiting
First Posted : November 30, 2017
Last Update Posted : November 30, 2017
Sponsor:
Information provided by (Responsible Party):
Stefan Zielen, 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.

Condition or disease Intervention/treatment Phase
Ataxia Telangiectasia 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 Not Applicable

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

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Susceptibility to Infections, Tumor Risk and Liver Disease in Patients With Ataxia Telangiectasia With and Without Substitution of Immunoglobulin G: a Prospective Observational Study
Actual Study Start Date : October 1, 2016
Estimated Primary Completion Date : September 30, 2018
Estimated Study Completion Date : September 30, 2019


Arm Intervention/treatment
A-T patients

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
Diagnostic Test: bioelectrical impedance analysis
Electrophysical measurement that allows to determine the exact composition of single body compartments by producing a magnetic field and detecting the potential difference through the body

Diagnostic Test: blood draw
Blood samples are taken from sober patients

Diagnostic Test: transient elastography (FibroScan)
FibroScan is a noninvasive tool to measure liver stiffness as an indication of fatty liver and liver fibrosis using ultrasound

Diagnostic Test: ataxia score
Klockgether ataxia score ranges from 0 to 35 points in which 0 means no symptoms and 35 stands for final stage of disease. It includes seven ataxia associated symptoms: dysarthria, intention tremor, ataxia of gait, stance, dysdiadochokinesia, upper limb and lower limb

Diagnostic Test: Five-Times-Sit-to-Stand Test
The test measures the complete time which is necessary for an individual to stand up and sit down on a chair five times in series




Primary Outcome Measures :
  1. Infections in A-T [ Time Frame: 24 months ]
    Evaluation of frequency, severity and intensity of infections in A-T patients with and without immunoglobulin G substitution


Secondary Outcome Measures :
  1. Liver disease [ Time Frame: 24 months ]
    Evaluation of the degree of liver disease measured by liver enzymes and structural changes by transient elastography (Fibroscan) in A-T patients

  2. Cancer risk [ Time Frame: 24 months ]
    Evaluation of tumor markers in A-T patients



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Ages Eligible for Study:   2 Years to 45 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03357978


Contacts
Contact: Sandra Woelke, Dr. 00496930183063 sandra.voss@kgu.de
Contact: Stefan Zielen, Prof. Dr. 00496930183063 stefan.zielen@kgu.de

Locations
Germany
Children's Hospital, Allergology, Pneumology and Cystic Fibrosis, Goethe University Frankfurt Recruiting
Frankfurt, Hessen, Germany, 60590
Contact: Sandra Wölke, Dr.    004969630183063    sandra.voss@kgu.de   
Contact: Stefan Zielen, Prof. Dr.    004969630183063    stefan.zielen@kgu.de   
Sponsors and Collaborators
Johann Wolfgang Goethe University Hospital
Investigators
Principal Investigator: Stefan Zielen, Prof. Dr. Children's Hospital, Allergology, Pneumology and Cystic Fibrosis, Goethe-University

Responsible Party: Stefan Zielen, Prof. Dr. med. Stefan Zielen, Johann Wolfgang Goethe University Hospital
ClinicalTrials.gov Identifier: NCT03357978     History of Changes
Other Study ID Numbers: InfectionandLiver_AT2016
First Posted: November 30, 2017    Key Record Dates
Last Update Posted: November 30, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Stefan Zielen, Johann Wolfgang Goethe University Hospital:
immunodeficiency
liver disease
cancer risk

Additional relevant MeSH terms:
Ataxia
Cerebellar Ataxia
Ataxia Telangiectasia
Spinocerebellar Ataxias
Liver Diseases
Disease Susceptibility
Telangiectasis
Digestive System Diseases
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Cerebellar Diseases
Brain Diseases
Central Nervous System Diseases
Disease Attributes
Pathologic Processes
Vascular Diseases
Cardiovascular Diseases
Neurocutaneous Syndromes
Genetic Diseases, Inborn
DNA Repair-Deficiency Disorders
Metabolic Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Immunoglobulins
Immunoglobulin G
Immunologic Factors
Physiological Effects of Drugs