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

Ataxia Telangiectasia Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03357978
• Other study ID #: InfectionandLiver_AT2016
• Status: Recruiting
• Phase: N/A
• First received: April 24, 2017
• Last updated: November 29, 2017
• Start date: October 1, 2016
• Est. completion date: September 30, 2019

Study information

• Verified date: November 2017
• Source: Johann Wolfgang Goethe University Hospital
• Contact: Sandra Woelke, Dr.
• Phone: 00496930183063
• Email: sandra.voss[@]kgu.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: September 30, 2019
• Est. primary completion date: September 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 45 Years

Eligibility

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)

Related Conditions & MeSH terms

• Ataxia
• Ataxia Telangiectasia
• Cerebellar Ataxia
• Disease Susceptibility
• Liver Diseases
• Telangiectasis

Intervention

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
• blood draw
Blood samples are taken from sober patients
• transient elastography (FibroScan)
FibroScan is a noninvasive tool to measure liver stiffness as an indication of fatty liver and liver fibrosis using ultrasound
• 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
• 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

Locations

Country	Name	City	State
Germany	Children's Hospital, Allergology, Pneumology and Cystic Fibrosis, Goethe University Frankfurt	Frankfurt	Hessen

Sponsors (1)

Lead Sponsor	Collaborator
Johann Wolfgang Goethe University Hospital

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Infections in A-T	Evaluation of frequency, severity and intensity of infections in A-T patients with and without immunoglobulin G substitution	24 months
Secondary	Liver disease	Evaluation of the degree of liver disease measured by liver enzymes and structural changes by transient elastography (Fibroscan) in A-T patients	24 months
Secondary	Cancer risk	Evaluation of tumor markers in A-T patients	24 months