Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT05300347 |
| Other study ID # |
TR-ADA-005 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
June 17, 2021 |
| Est. completion date |
June 17, 2023 |
Study information
| Verified date |
March 2022 |
| Source |
TRPHARM |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
This observational study was designed as a prospective epidemiological screening study.
Patients who applied to the centers participating in the study, bronchiectasis was detected
on at least one computed tomography of the lungs; Immunoglobulin E height and/or were found
to be lymphopenic on at least one examination will be included in the study. Up-to-date data
will be collected from patients who have agreed to participate in the study, and a blood
sample with DBS will be taken from patients. The blood taken will be subjected to analysis
for ADA metabolites. For patients with a high metabolic test, the responsible researcher will
advise on clarifying the diagnosis with a genetic test other than the study. In case of
formation of new information for each patient, consultation will be provided by the
responsible researcher. Thus, the prevalence of ADA enzyme deficiency disease in patients
with bronchiectasis, Immunoglobulin E elevation and/or lymphopenia will be evaluated. In
addition, with this study, it will be scientifically demonstrated whether lymphopenia and/or
Immunoglobulin E height is a parameter that facilitates the early diagnosis of patients with
late-onset ADA enzyme deficiency.
Description:
Bronchiectasis is a chronic disease characterized by abnormal and persistent expansion of the
bronchi. Although its frequency is not clearly known in our country, it is considered to be
53-566/100,000 in the Guidelines of the European Society of Respiratory Diseases. Of genetic
origin (cystic fibrosis, Primary ciliary dyskinesia, etc.), as well as recurrent lung
infections (pneumonia,viral infections, etc.) it can also develop depending on.
Bronchiectasis due to recurrent lung infections may occur in patients with primary
immunodeficiency. Primary immunodeficiency diseases are a group of diseases that are
accompanied by chronic and/or recurrent bacterial, fungal, protozoal and viral infections
that develop as a result of primary or congenital immunodeficiency. The incidence dec in
society varies from 1/10,000 to 1/100,000. Combined immunodeficiencies account for 15-29% of
primary immunodeficiencies. Severe Combined Immuno Deficiencies (SCID) are a heterogeneous
group of diseases caused by hereditary errors in genes involved in the development and/or
function of T, B, and sometimes NK cells, which cause serious dysfunction of the immune
system. The incidence is estimated at 1/100,000 live births in the United States. Although
the exact incidence of inbreeding is not known in our country, where inbreeding is common, it
is expected that those who show autosomal recessive transition will be more common,
especially. The recognition of these disorders by clinicians is important for reducing
long-term complications due to recurrent infections and preventing mortality with appropriate
treatment. The frequency of SCID in our country is unknown. Unlike in Europe and America,
SCID types, which are autosomal recessive in our country, are considered to be the most
common form due to high rates of inbreeding. The number obtained by comparing the number of
live babies born in a year in Konya with the number of AKIY cases diagnosed in the Pediatric
Immunology clinic of the Meram Faculty of Medicine of Selcuk University, the only primary
immunodeficiency diagnostic center in the region, in the same year, is 1/10,000. This
preliminary study shows that in our country this disease is much more common than in Europe
and America. To date, more than 20 genetic defects that cause SCID have been identified. All
known genetic defects disrupt the development of cells of the immune system, causing combined
immunodeficiency. One of them, the ADA defect, is also a metabolic disease, due to which
there is a lack of enzymes. ADA catalyzes the deamination of purine nucleosides adenosine
(Ado) and 2'-deoxyadenosine (dAdo), which are produced during the degradation and
transformation of RNA and DNA. ADA is a cleansing enzyme; it detoxifies purines. In ADA
deficiency, 2'-deoxyadenosine (dAdo) is phosphorylated and converted into deoxyadenosine
triphosphate (dATP). Accumulation of DATP disrupts DNA repair and replication. A high
percentage of dATP accumulates in ADA deficiency, especially in erythrocytes and lymphocytes.
Increased levels of adenosine break down the wall of the lymphocyte. It inhibits the
development of lymphocytes in the thymus. A kind of lymphocyte intoxication occurs. It leads
to a severe form of lymphopenia. Approximately 10-20% of AKIS are diagnosed as ADA enzyme
deficiency. It shows an autosomal recessive transition. Your gene is 20. it is localized on
the long arm of the chromosome. Clinically, there are early and late onset types.
Classic-early onset ADA deficiency: Although normal at birth, patients present with
infections seen from the first months of life, resulting in death if left untreated. In
addition to the AKI table, neuro-developmental disorders, sensorineural hearing loss and/or
skeletal abnormalities have also been reported in these patients. Although hematopoietic stem
cell transplantation, enzyme replacement therapy and gene therapy are treatment approaches
that provide cure, early diagnosis determines the prognosis.
Late onset ADA deficiency: Patients may present with recurrent infections, bronchiectasis,
autoimmunity, human papilloma virus (HPV) infections at an older age, even in adulthood.
Lymphopenia is an invariable finding. High IgE and eosinophilia may be observed. In these
cases, residual enzyme activity due to the type of mutation causes a late onset. This
phenotype accounts for 10-15% of all cases of ADA deficiency. Patients with late-onset ADA
enzyme deficiency appear in the form of case reports. in a study conducted in Zurich in 1997,
where the data of two patients were shared, it was observed that one patient had a history of
recurrent otitis and pulmonary infection, bronchiectasis, lymphopenia, and immunoglobulin E
elevation. The other patient, his cousin ADA, was diagnosed by chance while undergoing a bone
marrow scan due to enzyme deficiency. There is a history of recurrent tonsillitis. in a study
conducted by Hacettepe University published in 2018, the data of 13 patients with ADA enzyme
deficiency were evaluated, and 3 patients with late/delayed diagnosis were found to have ADA
enzyme deficiency. A patient with a late diagnosis of ADA enzyme deficiency was found to have
recurrent pneumonia, bronchiectasis, and Immunoglobulin E elevation. In the study in which
the data of a patient with a late onset ADA enzyme deficiency published in Konya from our
country in 2010 were shared, it was observed that the patient had a history of resection of
the lower left lobe due to bronchiectasis, lymphopenia and immunoglobulin E elevation.
Diagnosis: ADA enzyme deficiency is included in severe combined immunodeficiencies and is
observed with lymphopenia and infections. The diagnosis is made by measuring the activity of
the enzyme ADA in erythrocytes or lymphocytes in patients with suspected clinical and
laboratory features (such as lymphopenia, bronchiectasis). By mutation analysis, a gene
defect is shown. However, T-cell receptor excision circles (TREC) test is used for early
diagnosis. However, since the TREC test is found to be normal at birth in late-onset
patients, screening that leads patients to an early diagnosis can only be achieved by
measuring ADA metabolites. In late-onset ADA deficiency, it is difficult to diagnose. Low
awareness of the disease and its symptoms usually results in these cases not being diagnosed,
not being able to reach effective treatment, permanent organ damage and patient loss. For
this reason, diagnosis of patients is very important in terms of quality of life, as well as
vital importance. Reasons: ADA enzyme deficiencies account for approximately 15% of severe
combined immunodeficiencies. 15-20% of patients with ADA enzyme deficiency have a late
diagnosis of ADA enzyme deficiency. Because of the inability of these patients to get a
diagnosis, their treatment is also inadequate. This is the first time in our country.
the aim of the study is to investigate the ADA metabolites in the target group of adult
patients with bronchiectasis, lymphopenia and/or Immunoglobulin E elevation by looking at the
diagnosis and to obtain preliminary data on the prevalence of ADA disease.
