Natural History Study of Homocystinuria Caused by Cystathionine Beta-Synthase Deficiency (ACAPPELLA)

Study Overview
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Brief Summary
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The purpose of the study is to characterize the clinical course of homocystinuria in pediatric and adult patients aged 1 to 65 years under current clinical management practices

Official Title
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A Multicenter, Observational, Prospective, Natural History Study of Homocystinuria Due to Cystathionine Beta-synthase Deficiency in Pediatric and Adult Patients (ACAPPELLA)

Conditions
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Homocystinuria Due to CBS Deficiency

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who are clinically diagnosed with homocystinuria Male/female patients aged 1 to 65 years Patients who consented and/or assented Patients who are willing and able to comply with all study-related procedures. Exclusion Criteria: Medically significant postnatal complications or congenital anomalies that are not associated with homocystinuria Received any experimental therapy for homocystinuria during the 6 months prior to enrollment or expected to receive any such therapy during duration of the study

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Met cycle metabolites levels - tHcy | Changes in total homocysteine levels in micromoles. The met cycle metabolites levels and change from baseline will be summarized using descriptive statistics at each visit. | 6.5 years | 
| Changes in Met cycle metabolites levels - total Cys | Changes in total cysteine levels in micromoles. The met cycle metabolites levels and change from baseline will be summarized using descriptive statistics at each visit. | 6.5 years | 
| Changes in Met cycle metabolites levels - Met | Changes in total methionine levels in micromoles. The met cycle metabolites levels and change from baseline will be summarized using descriptive statistics at each visit. | 6.5 years | 
| Changes in Met cycle metabolites levels - Cth | Changes in total cystathionine levels in micromoles. The met cycle metabolites levels and change from baseline will be summarized using descriptive statistics at each visit. | 6.5 years | 
| Patient Reported Outcome (PRO): Quality of Life in Neurological Disorders [Neuro-QoL] | Short forms for four domains (anxiety, depression, social activities, cognition function) by adults version for age 18+ and pediatric version for age 12-17 are used. A summary score will be calculated for each domain by adding up the scores for individual questions. The aggregated score for each domain as a continuous variable, and the change from baseline in the aggregated domain score will be summarized using descriptive statistics at each visit. | 6.5 years | 
| Patient Reported Outcome (PRO): Quality of Life by 36-Item Short Form Survey [SF-36] | The original responses to all questions are scored on a scale from 0 to 100, with 100 representing the highest level possible. The rescaled scores that address each specific area of functional health status are averaged together, for a final score within each of the 8 domains measured. The average is based on the number of items with non-missing scores. The average score for each domain and the change from baseline will be summarized using descriptive statistics at each visit. | 6.5 years | 
| National Institutes of Health (NIH) Toolbox Cognition Battery | The NIH Toolbox is a multi-dimensional assessment tool that is used to measure the neurological and behavioral function of a patient over time. Assessments are recorded as 7 individual test scores, 1 total summary score and 2 composite scores. The raw measure scores and age-corrected standard scores and the change from baseline of the scores will be summarized using descriptive statistics at each visit. | 6.5 years | 
| EuroQol EQ-5D™ questionnaire to measure health and quality-of-life | EQ-5D™ is a standardized questionnaire as judged by the patients. This questionnaire consists of two parts: Five domains: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension consists of 5 levels of grading: no problem, slight problem, moderate problem, severe problem and extreme problem. For youths, 3 levels of grading: no problem, some problems, and a lot of problems. Visual analogue scale (VAS) is a vertical scale from 0 (worst) to 100 (best). Descriptive statistics will be provided for the five domains. Descriptive statistics will be provided for VAS and change from baseline at each visit for pooled EQ-5D-Y version and EQ-5D-5L version. | 6.5 years | 
| Dual-Energy X-Ray Absorptiometry to measure bone mineral density | The z-score, t-score, and bone mineral density and change from baseline will be summarized by the location of X-ray (spine, hip, and total body) at each visit. | 6.5 years | 
| Eye assessments to evaluate ocular health: Visual acuity examination will be performed to determine the clarity or sharpness of vision | Visual acuity examination will be performed to determine the clarity or sharpness of vision. The results will be summarized using descriptive statistics at each visit. | 6.5 years | 
| Eye assessments to evaluate ocular health: Slit lamp eye examination will be performed to look for any diseases or abnormalities in the anterior portion of the eye | Slit lamp eye examination will be performed to look for any diseases or abnormalities in the anterior portion of the eye. The results will be summarized using descriptive statistics at each visit. | 6.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Growth and development: World Health Organization (WHO) growth charts will be used to document height in centimeters (cm) for age 1 to 19 years old. Routine methods will be used to document height for all other age groups. | The results will be summarized using descriptive statistics at each visit. | 6.5 years | 
| Growth and development: World Health Organization (WHO) growth charts will be used to document Body Mass Index (BMI) in kilograms per meter square for age 1 to 19 years old. Routine methods will be used to document BMI for all other age groups. | The results will be summarized using descriptive statistics at each visit. | 6.5 years | 
| Growth and development: World Health Organization (WHO) growth charts will be used to document weight in kilograms (kg) for age 1 to 19 years old. Routine methods will be used to document weight for all other age groups. | The results will be summarized using descriptive statistics at each visit. | 6.5 years | 
| Changes in alanine aminotransferase (ALT) | The results will be summarized using descriptive statistics at each visit. | 6.5 years | 
| Changes in aspartate aminotransferase (AST) | The results will be summarized using descriptive statistics at each visit. | 6.5 years | 
| Changes in alkaline phosphatase (ALP) | The results will be summarized using descriptive statistics at each visit. | 6.5 years | 
| Optional homocystynuria genetic testing |  | The optional test will be done once at screening visit |