An Observational Study for Evaluation of for the Prevalence of Cerebrotendinous Xanthomatosis (CTX) Disease (GEN-EYE-II)

An Epidemiological Observational Study for Retrospective and Prospective Evaluation of for the Prevalence of Cerebrotendinous Xanthomatosis (CTX) Disease in Neurology and Pediatric Metabolism Clinics in Turkey

The prevalence of CTX in our country is estimated to be 1 / 50.000. The aim of this study is to screen more volunteers by conducting a larger screening from neurology and pediatric metabolism clinics in Turkey.

This observational study was designed retrospectively and prospectively in two stages. In the retrospective section, the patient database and / or patient files will be screened in the neurology and pediatric metabolism clinics and the patients aged 40 and below in the neurology clinics with at least two of the following will be enrolled to the study:

• Ataxia and / or spasticity
• Bilateral cataract (except senile cataract)
• Intellectual limitation
• Non-enhancing hyperintensity on T2 sections in MR imaging of dentate nuclei
• Autosomal recessive transition pattern. (Ex: Relative Marriage)

In the pediatric metabolism centers, cases suspected of CTX and planned to apply the Mignarri Index according to the investigator's opinion will be identified.

Study Overview

• Status: Terminated
• Conditions: CTX - Cerebrotendinous Xanthomatosis
• Intervention / Treatment: Other: Blood sampling for cholestanol analysis

• Study Type: Observational
• Enrollment (Actual): 22

Contacts and Locations

Study Locations

• Turkey
  • Adana, Turkey
    • Çukurova University Medical Faculty Deparment of Metabolism
  • Adana, Turkey
    • Çukurova University Medical Faculty Department of Neurology
  • Ankara, Turkey
    • Ankara City Hospital
  • Ankara, Turkey
    • Ankara Child and Heamatology Hospital Deparment of Metabolism
  • Ankara, Turkey
    • Ankara Dışkapı Yıldırım Beyazıt Research and Training Hospital Clinic of Neurology
  • Ankara, Turkey
    • Gazi University Medical Faculty Department of Pediatric Metabolism
  • Ankara, Turkey
    • Hacettepe University Medical Faculty Deparment of Metabolism
  • Ankara, Turkey
    • Hacettepe University Medical Faculty Department of Neurology
  • Eskişehir, Turkey
    • Osmangazi University Medical Faculty Department of Neurology
  • Eskişehir, Turkey
    • Osmangazi University Medical Faculty Department of Pediatric Metabolism
  • Istanbul, Turkey
    • Bezmi Alem Vakıf University Medical Faculty Department of Neurology
  • Istanbul, Turkey
    • Hamidiye Şişli Etfal Research and Training Hospital Clinic of Neurology
  • Istanbul, Turkey
    • Hamidiye Şişli Etfal Research and Training Hospital Clinic of Pediatric Metabolism
  • Istanbul, Turkey
    • İstanbul University Cerrahpasa Medical Faculty Department of Pediatric Metabolism
  • Istanbul, Turkey
    • İstanbul University Cerrahpaşa Medical Faculty Department of Neurology
  • Istanbul, Turkey
    • İstanbul University İstanbul Medical Faculty Department of Neurology
  • Istanbul, Turkey
    • İstanbul University İstanbul Medical Faculty Department of Pediatric Metabolism
  • Istanbul, Turkey
    • Kanuni Sultan Suleyman Research and Training Hospital Clinic of Pediatric Metabolism
  • Istanbul, Turkey
    • Medeniyet University Göztepe Research and Training Hospital Clinic of Neurology
  • Mersin, Turkey
    • Mersin City Hospital Department of Metabolism
  • Mersin, Turkey
    • Mersin University Medical Faculty Department of Neurology
  • Sivas, Turkey
    • Cumhuriyet University Medical Faculty Department of Neurology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 40 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

200 patients

Description

Inclusion Criteria:

I-1. Giving written informed consent

I-2. Patients in neurology clinics should have been identified with at least two of the following:

• Ataxia and / or spasticity
• Bilateral cataract (except senile cataract)
• Intellectual limitation
• Nonintensitive hyperintensity in T2 sections on MRI of the dentate nucleus
• Forming an autosomal recessive transition pattern. (Ex: Relative Marriage)

I-3. In the pediatric metabolism centers, cases suspected of CTX and planned to apply the Mignarri Index according to the investigator's opinion.

I-4. On the day the patient signed the Informed Consent Form, the patient did not get older than 41 years of age (subjects aged 40 and under will be included in the study)

Exclusion Criteria:

E-1. The patient's ataxia and / or spasticity, cataract, intellectual limitation, and non-contrasted hyperintensity of T2 sections in MR imaging of dentate nuclei with typical MRI findings are due to a known cause other than CTX or other underlying disease.

E-2. The patient has participated in an interventional clinical study in the last 30 days,

E-3. The patient and / or his / her legal representative does not give consent to participate in the study,

E-4. In the opinion of the investigator, the patient is not able to fulfill the working requirements appropriately,

E-5. Pregnancy and / or lactation

E-6. If the patient was 41 years old when included in the study.

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Other

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with CTX possibility in Neurology Clinics	- Proportion of patients aged 40 years or younger with at least two of the following (2) in patients with a cholestanol test threshold (3.75 mg / mL) in neurology clinics: Ataxia and / or spasticity; Bilateral cataract (except senile cataract); Intellectual limitation; Nonintensitive hyperintensity in T2 sections on MRI of the dentate nucleus; Forming an autosomal recessive transition pattern. (Ex: Relative Marriage)	3 years
Proportion of patients with CTX possibility in Pediatric Metabolism Clinics	- Proportion of cases above the cholestanol test threshold (3.75 mg / mL) in pediatric metabolism centers	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total of Mignarri Suspicion Index (SI)	Mignarri is a suspicion index, composed of weight-ed scores assigned to indicators such as family history and common systemic and neurological features. The indicators were classified as very strong (score 100), strong (50) or moderate (25). The suspicion index will be applied to study population. Early systemic signs such as catamct, diarrhea and neonatal cholestatic jaundice were considered strong indica- tors, together with neurological features such as intellectual impairment, psychiatric disturbances, ataxia, spastic paraparesis and dentate nuclei abnormalities at MRI. Tendon xanthomas were regarded as very strong indicators, as was an affected sibling. A total score 100 warranted serum cholestanol assessment. Elevated cholestanol or a total score 200, with one very strong or four strong indicators, warranted CYP27Al gene analysis. (Reference: Mignarri et al. J Inherit Metab Dis (2014) 37:421-429) -and physical examination results for patients with high cholestanol levels	3 Years
Cholestanol Levels	- Cholestanol levels for patients with high cholestanol levels	3 Years
Patient demographics	For all screened patients: • Demographic data	3 Years
CTX Family History	For all screened patients: • CTX family history	3 Years
Presence of consangunious marriage	For all screened patients: • Presence of consanguineous marriage	3 Years
Frequency of the systemic findings	For all screened patients: • Frequency of the following systemic findings: Tendon xanthomas; Chronic diarrhea; Prolonged neonatal jaundice; Early osteoporosis	3 Years
Frequency of the neurologic findings	For all screened patients: • Frequency of the following neurological symptoms: Cerebellar ataxia; Spastic paraparesis; Blateral cataract (except senile cataract); Non-enhancing hyperintensity on T2 sections in MR imaging of dentate nuclei; Intellectual disability; Psychiatric disorders; Epilepsy; Parkinson's; Polyneuropathy	3 Years

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): October 19, 2019
• Primary Completion (Actual): March 16, 2022
• Study Completion (Actual): June 10, 2022

Study Registration Dates

• First Submitted: September 25, 2019
• First Submitted That Met QC Criteria: October 1, 2019
• First Posted (Actual): October 2, 2019

Study Record Updates

• Last Update Posted (Actual): June 15, 2022
• Last Update Submitted That Met QC Criteria: June 10, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Lipid Metabolism, Inborn Errors; Xanthomatosis, Cerebrotendinous; Xanthomatosis; Physiological Effects of Drugs; Micronutrients; Vitamins; Provitamins; Dehydrocholesterols
• Other Study ID Numbers: TR-CTX-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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