The Prevalence of CTX Disorder in Juvenile Cataract Cases in Turkey

Cerebrotendinous Xanthomatosis Clinical Trial

— GEN-EYE-I  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03584893
• Other study ID #: TR-CTX-001
• Status: Recruiting
• Start date: June 1, 2018
• Est. completion date: March 1, 2023

Study information

• Verified date: March 2021
• Source: TRPHARM
• Contact: Serdar Altinel
• Phone: 00902123863149
• Email: serdar.altinel[@]trpharm.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: March 1, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year and older

Eligibility

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.

Related Conditions & MeSH terms

• Cataract
• Cerebrotendinous Xanthomatosis
• Xanthomatosis, Cerebrotendinous

Intervention

Procedure:
• Blood sampling for Cholestanol Analysis
Cholestanol analysis will be performed to see the Rate of juvenile cataract patients whose cholestanol test result is above threshold (3.75 mg/mL) and suspected CTX cases

Locations

Country	Name	City	State
Turkey	Adana Baskent University School of Medicine	Adana
Turkey	Adana State Hospital	Adana
Turkey	Çukurova University Medical Faculty Department of Ophtalmology	Adana
Turkey	Ankara Training and Research Hospital	Ankara
Turkey	Ankara University Medical Faculty Department of Ophtalmology	Ankara
Turkey	Baskent University School of Medicine	Ankara
Turkey	Dünya Göz Hospital	Ankara
Turkey	Hacettepe University Medical Faculty Department of Ophtalmology	Ankara
Turkey	Health Sciences University Ankara State Hospital	Ankara
Turkey	SBU Gülhane Training and Research Hospital	Ankara
Turkey	Ulucanlar Göz Training Hospital	Ankara
Turkey	Akdeniz University Medical Faculty Department of Ophtalmology	Antalya
Turkey	Bursa Yüksek Ihtisas Training and Research Hospital	Bursa
Turkey	Uludag University Medical Faculty Department of Ophtalmology	Bursa
Turkey	Dicle University School of Medicine	Diyarbakir
Turkey	Firat University School of Medicine	Elazig
Turkey	Osmangazi University Medical Faculty Department of Ophtalmology	Eskisehir
Turkey	Gaziantep University Sahinbey Training and Research Hospital	Gaziantep
Turkey	Istanbul Haseki Training and Research Hospital	Istanbul
Turkey	Istanbul Health Sciences University Kanuni Sultan Süleyman Training and Research Hospital	Istanbul
Turkey	Istanbul University Istanbul Medical Faculty Department of Ophtalmology	Istanbul
Turkey	Marmara University Medical Faculty Department of Ophtalmology	Istanbul
Turkey	Marmara University Pendik Training and Research Hospital	Istanbul
Turkey	Prof.Dr.N.Resat Belger Beyoglu Göz Training and Research Hospital	Istanbul
Turkey	Dokuz Eylül University Medical Faculty Department of Ophtalmology	Izmir
Turkey	Ege University Medical Faculty Department of Ophtalmology	Izmir
Turkey	Izmir Dr. Behcet Uz Child Diseases and Surgery Training and Research Hospital	Izmir
Turkey	Kayseri Training and Research Hospital	Kayseri
Turkey	Kocaeli University School of medicine	Kocaeli
Turkey	Inönü University School of Medicine	Malatya
Turkey	Mersin University Medical Faculty Department of Ophtalmology	Mersin
Turkey	Sakarya University School of Medicine	Sakarya
Turkey	Ondokuz Mayis University School of Medicine	Samsun
Turkey	Harran University Research and Application Hospital	Sanliurfa
Turkey	Karadeniz Technical University School of Medicine	Trabzon
Turkey	Van 100. Yil University Dursun Odabas Medical Center	Van

Sponsors (3)

Lead Sponsor	Collaborator
TRPHARM	Düzen Laboratories Group, Klinar CRO

Country where clinical trial is conducted

Turkey, 

References & Publications (11)

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. — View 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

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. — View Citation

Federico A, Dotti MT, Gallus GN (2003) Cerebrotendinous Xanthomatosis. In: Pagon RA, Adam MP, Ardinger HH, et al. (eds) GeneReviews Seattle (WA): University of Washington, Seattle, 1993- 2017 (updated 2016 Apr 14)

Fraidakis MJ. Psychiatric manifestations in cerebrotendinous xanthomatosis. Transl Psychiatry. 2013 Sep 3;3:e302. doi: 10.1038/tp.2013.76. Review. — View 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. — View 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. — View 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. Review. — View 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. Review. — View Citation

Verrips A, Hoefsloot LH, Steenbergen GC, Theelen JP, Wevers RA, Gabreëls 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. — View 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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of juvenile cataract patients	Rate of juvenile cataract patients whose cholestanol test result is above threshold (3.75 mg/mL) and suspected CTX cases	"through study completion, an average of 3 years"
Secondary	CTX history in family	The history of the disease will be assessed from the patient records and by interview	"through study completion, an average of 3 years"
Secondary	Presence of consanguineous marriage	Presence of consanguineous marriage	"through study completion, an average of 3 years"
Secondary	The frequency of the systemic findings	The frequency of the following systemic findings: Tendon xanthomas; Chronic diarrhea; Prolonged neonatal jaundice; Early osteoporosis	"through study completion, an average of 3 years"
Secondary	The frequency of the neurological symptoms	The frequency of the following neurological symptoms: Cerebellar ataxia; Spastic paraparesis; Disruption of dentate nucleus signal detected by MRI; Intellectual disability; Psychiatric disorders; Epilepsy; Parkinson; Polyneuropathy	"through study completion, an average of 3 years"