Clinical trial NCT03584893: The Prevalence of CTX Disorder in Juvenile Cataract Cases in Turkey
Official title: An Observational Study With Retrospective and Prospective Evaluations to Determine the Prevalence of Cerebrotendinous Xanthomatosis (CTX) Disorder in Juvenile Cataract Cases in Turkey
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Cerebrotendinous Xanthomatosis
Keywords: Juvenile Cataract
CTX
Diarrhea
Neonatal Jaundice
Xanthoma
Lead sponsor: TRPHARM
Sponsor class: INDUSTRY
Collaborators: name: Klinar CRO
name: Düzen Laboratories Group
First posted: 2018-07-12
Enrollment: 1000
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: PROBABILITY_SAMPLE
Study population: All patients over 1 year old diagnosed as idiopathic bilateral juvenile cataracts will be included in the study at the study sites.

Brief summary: Epidemiologic observational study. Study will include two phases:

1. Retrospective cross-sectional phase: At this stage of the study, retrospective screenings are carried out at study sites and all juvenile cataract cases are planned to be determined.
2. Prospective phase: At this stage of the study, identified juvenile cataract cases as a result of retrospective screenings will be called to be invited to the sites and blood samples will be obtained for the cholestanol tests for the cases that have given Informed Consent.

This observational study is designed in two phases; retrospective and prospective. Retrospective part includes screening the patient database and / or patient files at ophthalmology clinics participating in the study and identifying patients diagnosed with idiopathic juvenile cataracts. The data of patients with idiopathic juvenile cataracts will be reviewed and the data of the patients meeting the inclusion/exclusion criteria will be recorded. Once this phase is completed, the prospective phase of the study will start and the patients meeting the criteria will be invited to the site to participate in the study. Current data will be collected from the patients who agree to participate in the study and the clinical status of the patients will be evaluated according to the Mignarri index. In addition, blood will be obtained from all patients to diagnose CTX disease. Blood samples will be sent to Duzen Laboratories in Ankara and analyzed for cholestanol.


Eligibility criteria: Inclusion Criteria:

* Providing the written informed consent form
* The patient should be diagnosed with idiopathic bilateral juvenile cataract
* Idiopathic bilateral juvenile cataract should be diagnosed while the patient must be take a day from one year (age)
* Syria ciziten who take their citizenship of Turkey could be enrolled to the study after signing of Informed Consent Form that translated to mother tongue by sworn translation office approved by ethic committee.

Exclusion Criteria:

* If the patient has been diagnosed with CTX before his/her enrollment in the study,
* If the patient has been diagnosed with cataract due to any known reasons other than CTX including cataracts related to trauma,
* If the patient has been diagnosed with cataract due to cataractogenic treatments,
* If the patient has participated in an interventional clinical study within the last 30 days,
* If the patient and/or his/her legal representative does not provide consent to participate in the study,
* If the patient will not be able to fulfill study requirements according to the investigator's opinion,
* If the patient had used cholic acid or chenodeoxycholic acid on or before the date of participation in the study
* Pregnancy and/or lactation
* Syria citizen that have not Turkey citizenship will not enroll to the study.

Primary outcomes:
measure: Rate of juvenile cataract patients
timeFrame: "through study completion, an average of 3 years"
Secondary outcomes:
measure: CTX history in family
timeFrame: "through study completion, an average of 3 years"
measure: Presence of consanguineous marriage
timeFrame: "through study completion, an average of 3 years"
measure: The frequency of the systemic findings
timeFrame: "through study completion, an average of 3 years"
measure: The frequency of the neurological symptoms
timeFrame: "through study completion, an average of 3 years"
Other outcomes:
Locations:
city: Adana
country: Turkey
facility: Adana Başkent University School of Medicine
city: Adana
country: Turkey
facility: Adana State Hospital
city: Adana
country: Turkey
facility: Çukurova University Medical Faculty Department of Ophtalmology
city: Ankara
country: Turkey
facility: Ankara Training and Research Hospital
city: Ankara
country: Turkey
facility: Ankara University Medical Faculty Department of Ophtalmology
city: Ankara
country: Turkey
facility: Başkent University School of Medicine
city: Ankara
country: Turkey
facility: Dünya Göz Hospital
city: Ankara
country: Turkey
facility: Hacettepe University Medical Faculty Department of Ophtalmology
city: Ankara
country: Turkey
facility: Health Sciences University Ankara State Hospital
city: Ankara
country: Turkey
facility: SBU Gülhane Training and Research Hospital
city: Ankara
country: Turkey
facility: Ulucanlar Göz Training Hospital
city: Antalya
country: Turkey
facility: Akdeniz University Medical Faculty Department of Ophtalmology
city: Bursa
country: Turkey
facility: Bursa Yüksek İhtisas Training and Research Hospital
city: Bursa
country: Turkey
facility: Uludağ University Medical Faculty Department of Ophtalmology
city: Diyarbakır
country: Turkey
facility: Dicle University School of Medicine
city: Elazığ
country: Turkey
facility: Fırat University School of Medicine
city: Eskişehir
country: Turkey
facility: Osmangazi University Medical Faculty Department of Ophtalmology
city: Gaziantep
country: Turkey
facility: Gaziantep University Şahinbey Training and Research Hospital
city: Istanbul
country: Turkey
facility: İstanbul Haseki Training and Research Hospital
city: Istanbul
country: Turkey
facility: İstanbul Health Sciences University Kanuni Sultan Süleyman Training and Research Hospital
city: Istanbul
country: Turkey
facility: Istanbul University Istanbul Medical Faculty Department of Ophtalmology
city: Istanbul
country: Turkey
facility: Marmara University Medical Faculty Department of Ophtalmology
city: Istanbul
country: Turkey
facility: Marmara University Pendik Training and Research Hospital
city: Istanbul
country: Turkey
facility: Prof.Dr.N.Reşat Belger Beyoğlu Göz Training and Research Hospital
city: İzmir
country: Turkey
facility: Dokuz Eylül University Medical Faculty Department of Ophtalmology
city: İzmir
country: Turkey
facility: Ege University Medical Faculty Department of Ophtalmology
city: İzmir
country: Turkey
facility: İzmir Dr. Behcet Uz Child Diseases and Surgery Training and Research Hospital
city: Kayseri
country: Turkey
facility: Kayseri Training and Research Hospital
city: Kocaeli
country: Turkey
facility: Kocaeli University School of medicine
city: Malatya
country: Turkey
facility: İnönü University School of Medicine
city: Mersin
country: Turkey
facility: Mersin University Medical Faculty Department of Ophtalmology
city: Sakarya
country: Turkey
facility: Sakarya University School of Medicine
city: Samsun
country: Turkey
facility: Ondokuz Mayıs University School of Medicine
city: Trabzon
country: Turkey
facility: Karadeniz Technical University School of Medicine
city: Van
country: Turkey
facility: Van 100. Yıl University Dursun Odabaş Medical Center
city: Şanlıurfa
country: Turkey
facility: Harran University Research and Application Hospital
Study officials:
References:
citation: Clayton PT (2016) Disorders of Bile Acid Synthesis. In: Saudubray JM, Baumgartner MR, Walter J (eds) Inborn metabolic diseases: diagnosis and treatment, 6th ed. Springer-Verlag, Heidelberg, pp 465- 477
citation: Nie S, Chen G, Cao X, Zhang Y. Cerebrotendinous xanthomatosis: a comprehensive review of pathogenesis, clinical manifestations, diagnosis, and management. Orphanet J Rare Dis. 2014 Nov 26;9:179. doi: 10.1186/s13023-014-0179-4.
citation: Federico A, Gallus GN. Cerebrotendinous Xanthomatosis. 2003 Jul 16 [updated 2024 Nov 14]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from http://www.ncbi.nlm.nih.gov/books/NBK1409/
citation: Fraidakis MJ. Psychiatric manifestations in cerebrotendinous xanthomatosis. Transl Psychiatry. 2013 Sep 3;3(9):e302. doi: 10.1038/tp.2013.76.
citation: Cruysberg JR, Wevers RA, Tolboom JJ. Juvenile cataract associated with chronic diarrhea in pediatric cerebrotendinous xanthomatosis. Am J Ophthalmol. 1991 Nov 15;112(5):606-7. doi: 10.1016/s0002-9394(14)76874-6. No abstract available.
citation: Mignarri A, Gallus GN, Dotti MT, Federico A. A suspicion index for early diagnosis and treatment of cerebrotendinous xanthomatosis. J Inherit Metab Dis. 2014 May;37(3):421-9. doi: 10.1007/s10545-013-9674-3. Epub 2014 Jan 18.
citation: Verrips A, Hoefsloot LH, Steenbergen GC, Theelen JP, Wevers RA, Gabreels FJ, van Engelen BG, van den Heuvel LP. Clinical and molecular genetic characteristics of patients with cerebrotendinous xanthomatosis. Brain. 2000 May;123 ( Pt 5):908-19. doi: 10.1093/brain/123.5.908.
citation: Salen G, Steiner RD. Epidemiology, diagnosis, and treatment of cerebrotendinous xanthomatosis (CTX). J Inherit Metab Dis. 2017 Nov;40(6):771-781. doi: 10.1007/s10545-017-0093-8. Epub 2017 Oct 4.
citation: Cali JJ, Hsieh CL, Francke U, Russell DW. Mutations in the bile acid biosynthetic enzyme sterol 27-hydroxylase underlie cerebrotendinous xanthomatosis. J Biol Chem. 1991 Apr 25;266(12):7779-83.
citation: Yahalom G, Tsabari R, Molshatzki N, Ephraty L, Cohen H, Hassin-Baer S. Neurological outcome in cerebrotendinous xanthomatosis treated with chenodeoxycholic acid: early versus late diagnosis. Clin Neuropharmacol. 2013 May-Jun;36(3):78-83. doi: 10.1097/WNF.0b013e318288076a.
citation: Khan AO, Aldahmesh MA, Mohamed JY, Alkuraya FS. Juvenile cataract morphology in 3 siblings not yet diagnosed with cerebrotendinous xanthomatosis. Ophthalmology. 2013 May;120(5):956-60. doi: 10.1016/j.ophtha.2012.10.032. Epub 2013 Jan 31.