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

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

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

Study Overview

• Status: Completed
• Conditions: Homocystinuria Due to CBS Deficiency

• Study Type: Observational
• Enrollment (Actual): 110

Contacts and Locations

Study Locations

• Ireland
  • Dublin, Ireland, 1
    • Temple Street Children's University Hospital
• Qatar
  • Doha, Qatar
    • Hamad Medical Corporation
  • Qatar
    • Doha, Qatar, Qatar
      • Sidra Medicine
• United Kingdom
  • Manchester
    • Salford, Manchester, United Kingdom, M6 8HD
      • Salford Royal NHS Foundation Trust
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • The Children's Hospital of Colorado
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Children's National Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • North Carolina
    • Morrisville, North Carolina, United States, 27560
      • Science 37 - Virtual Site for the US and Canada
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Clinical site

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

What is the study measuring?

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 homocystinuria genetic testing		The optional test will be done once at screening visit

Collaborators and Investigators

• Sponsor: Travere Therapeutics, Inc.
• Investigators: Study Director: Michael Imperiale, MD, Travere Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Actual): July 31, 2026
• Study Completion (Actual): July 31, 2026

Study Registration Dates

• First Submitted: December 2, 2016
• First Submitted That Met QC Criteria: December 16, 2016
• First Posted (Estimated): December 20, 2016

Study Record Updates

• Last Update Posted (Actual): September 9, 2026
• Last Update Submitted That Met QC Criteria: September 3, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Connective Tissue Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Amino Acid Metabolism, Inborn Errors; Hyperhomocysteinemia; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Skin and Connective Tissue Diseases; Homocystinuria
• Other Study ID Numbers: CBS-HCY-NHS-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Requests for clinical trial data, including language stating its intended use, should be directed to datarequest@travere.com. If approved, the requested information will be provided to the requestor after signing a data access agreement. Requests can be made following completion of the study and full publication of the study data in a peer reviewed journal for up to 36 months following its publication. Travere reserves the right to decline or recommend modifications to a request if it does not comply with the data sharing policy or if it is determined that the request is made by a biased source.
• IPD Sharing Time Frame: Requests can be made following completion of the study and full publication of the study data in a peer reviewed journal for up to 36 months following its publication.
• IPD Sharing Access Criteria: Requires submission and approval of intended use and a data sharing agreement.