The Prevalence of CTX Disorder in Juvenile Cataract Cases in Turkey (GEN-EYE-I)

An Observational Study With Retrospective and Prospective Evaluations to Determine the Prevalence of Cerebrotendinous Xanthomatosis (CTX) Disorder in Juvenile Cataract Cases in Turkey

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.

Study Overview

• Status: Recruiting
• Conditions: Cerebrotendinous Xanthomatosis
• Intervention / Treatment: Procedure: Blood sampling for Cholestanol Analysis

• Study Type: Observational
• Enrollment (Anticipated): 1000

Contacts and Locations

• Study Contact: Name: Serdar Altinel; Phone Number: 00902123863149; Email: serdar.altinel@trpharm.com

Study Locations

• Turkey
  • Adana, Turkey
    • Not yet recruiting
    • Adana Başkent University School of Medicine
    • Contact: Aysel Pelit
  • Adana, Turkey
    • Recruiting
    • Adana State Hospital
  • Adana, Turkey
    • Recruiting
    • Çukurova University Medical Faculty Department of Ophtalmology
  • Ankara, Turkey
    • Recruiting
    • Ankara Training and Research Hospital
  • Ankara, Turkey
    • Recruiting
    • Ankara University Medical Faculty Department of Ophtalmology
  • Ankara, Turkey
    • Recruiting
    • Başkent University School of Medicine
  • Ankara, Turkey
    • Recruiting
    • Dunya Goz Hospital
  • Ankara, Turkey
    • Recruiting
    • Hacettepe University Medical Faculty Department of Ophtalmology
  • Ankara, Turkey
    • Recruiting
    • Health Sciences University Ankara State Hospital
  • Ankara, Turkey
    • Recruiting
    • SBU Gulhane Training and Research Hospital
  • Ankara, Turkey
    • Recruiting
    • Ulucanlar Göz Training Hospital
  • Antalya, Turkey
    • Recruiting
    • Akdeniz University Medical Faculty Department of Ophtalmology
  • Bursa, Turkey
    • Recruiting
    • Bursa Yuksek Ihtisas Training and Research Hospital
  • Bursa, Turkey
    • Terminated
    • Uludağ University Medical Faculty Department of Ophtalmology
  • Diyarbakır, Turkey
    • Terminated
    • Dicle University School of Medicine
  • Elazığ, Turkey
    • Recruiting
    • Fırat University School of Medicine
  • Eskişehir, Turkey
    • Recruiting
    • Osmangazi University Medical Faculty Department of Ophtalmology
  • Gaziantep, Turkey
    • Recruiting
    • Gaziantep University Sahinbey Training and Research Hospital
  • Istanbul, Turkey
    • Recruiting
    • Istanbul Haseki Training and Research Hospital
    • Contact: Nilgün Solmaz
  • Istanbul, Turkey
    • Recruiting
    • İstanbul Health Sciences University Kanuni Sultan Süleyman Training and Research Hospital
  • Istanbul, Turkey
    • Recruiting
    • Istanbul University Istanbul Medical Faculty Department of Ophtalmology
  • Istanbul, Turkey
    • Recruiting
    • Marmara University Medical Faculty Department of Ophtalmology
  • Istanbul, Turkey
    • Not yet recruiting
    • Marmara University Pendik Training and Research Hospital
    • Contact: Eren Çerman
  • Istanbul, Turkey
    • Recruiting
    • Prof.Dr.N.Reşat Belger Beyoğlu Göz Training and Research Hospital
  • Kayseri, Turkey
    • Recruiting
    • Kayseri Training and Research Hospital
  • Kocaeli, Turkey
    • Recruiting
    • Kocaeli University School of Medicine
    • Contact: Dilara Pirhan
  • Malatya, Turkey
    • Terminated
    • Inönü University School of Medicine
  • Mersin, Turkey
    • Recruiting
    • Mersin University Medical Faculty Department of Ophtalmology
  • Sakarya, Turkey
    • Recruiting
    • Sakarya University School of Medicine
    • Contact: Erkan Çelik
  • Samsun, Turkey
    • Recruiting
    • Ondokuz Mayıs University School of Medicine
  • Trabzon, Turkey
    • Recruiting
    • Karadeniz Technical University School of Medicine
  • Van, Turkey
    • Recruiting
    • Van 100. Yıl University Dursun Odabaş Medical Center
  • İzmir, Turkey
    • Recruiting
    • Dokuz Eylül University Medical Faculty Department of Ophtalmology
  • İzmir, Turkey
    • Recruiting
    • Ege University Medical Faculty Department of Ophtalmology
  • İzmir, Turkey
    • Recruiting
    • İzmir Dr. Behcet Uz Child Diseases and Surgery Training and Research Hospital
  • Şanlıurfa, Turkey
    • Recruiting
    • Harran University Research and Application Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Epidemiologic observational study cohort; All patients over 1 year old diagnosed as idiopathic bilateral juvenile cataracts will be included in the study at the study sites.	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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"
Presence of consanguineous marriage	Presence of consanguineous marriage	"through study completion, an average of 3 years"
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"
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"

Collaborators and Investigators

• Sponsor: TRPHARM
• Collaborators: Klinar CRO; Düzen Laboratories Group

Publications and helpful links

General Publications

• 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
• 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.
• 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(9):e302. doi: 10.1038/tp.2013.76.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2018
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): March 1, 2023

Study Registration Dates

• First Submitted: June 19, 2018
• First Submitted That Met QC Criteria: July 11, 2018
• First Posted (Actual): July 12, 2018

Study Record Updates

• Last Update Posted (Actual): March 29, 2021
• Last Update Submitted That Met QC Criteria: March 25, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Diarrhea; Juvenile Cataract; CTX; Neonatal Jaundice; Xanthoma
• Additional Relevant MeSH Terms: Metabolic Diseases; Eye Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lens Diseases; Lipid Metabolism Disorders; Lipid Metabolism, Inborn Errors; Cataract; Xanthomatosis, Cerebrotendinous; Xanthomatosis; Physiological Effects of Drugs; Micronutrients; Vitamins; Provitamins; Dehydrocholesterols
• Other Study ID Numbers: TR-CTX-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No