A One Visit Follow Up of Adults With Fabry Disease Who Started Long-term Enzyme Replacement Therapy As Children

Study Overview
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Brief Summary
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The objective of this study is to obtain follow up data on a cohort of well-studied patients with Fabry disease who have been on ERT since childhood for a total of about 15 years.

Detailed Description
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The long-term effect of initiating ERT in childhood is unknown. Prospective studies of Children with Fabry disease on 0.2 mg/kg agalsidase alfa every other week were performed. The patients were 7-17 years of age at initial study enrollment. The first open-label protocol was TKT023, a 6 months study (August 12, 2002-October 20, 2004) that was followed by an extension study TKT029 (June 10, 2004-June 15, 2011; ClinicalTrials.gov identifier NCT00084084). Since completing TKT029, all US patients were switched to commercial agalsidase beta. Therefore, these patients have now been treated for about 15 years.This study involves a one-visit follow up on these patients using the same protocol-driven studies as were used in TKT029. The long-term follow up data gathered will consist of a rare description of the disease profile in patients who were treated with ERT since childhood.

Official Title
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A One Visit Follow Up of Adults With Fabry Disease Who Started Long-term Enzyme Replacement Therapy As Children

Conditions
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Quality of Life, Renal Insufficiency, Cardiac Event

Intervention / Treatment
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* Other: General and Neurological examination
* Other: Vital signs
* Procedure: 12 lead electrocardiogram
* Procedure: Echocardiogram
* Procedure: Blood draw
* Procedure: Urine collection
* Procedure: 2-hour Holter Monitor
* Other: Brief Pain Inventory questionnaire
* Other: Quality of Life questionnaire


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who participated in TKT029 and who are willing and able to come to Dallas for 1 visit for standard of care testing. Sign the protocol informed consent form Have been on continuous commercial ERT since TKT029 has ended Exclusion Criteria: Patients who are unable to understand the nature, scope, and possible consequences of the study. Patient does not give his written informed consent to participate in this study Patient is unable to comply with the protocol, e.g., uncooperative with protocol schedule, refusal to agree to all of the study procedures. Patient has been off ERT for an extended period of time as assessed by the investigator.

Ages Eligible for Study
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Minimum Age: 18 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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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Interventional Model Description: Specific group of adults with Fabry disease who received Replagal infusions as children
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Single Visit<br>General and neurological examination Vital signs including height, weight, blood pressure, pulse, temperature 12 lead ECG 2 hour Holter monitor for heart rate variability Echocardiogram Renal function will be assessed by the eGFR. The eGFR will be calculated from serum creatinine using CKD-EPI equation. CBC with differential Complete metabolic panel Urinalysis Urine Albumin/creatinine ratio. Urine and plasma samples for biomarkers (Gb3, lyso-Gb3) that will be stored in -80 freezer and assayed in our lab. Brief Pain Inventory questionnaire. Quality of Life Questionnaires (SF36) | Other: General and Neurological examination<br>* Information about your general health, neurological symptoms and current medications with be collected<br>* Other names: MD assessment;Other: Vital signs<br>* Height, weight, blood pressure, heart rate, and respiratory rate and temperature will be measured.<br>* Other names: Blood pressure, heart rate, respiratory rate;Procedure: 12 lead electrocardiogram<br>* A non-invasive test that measures the electrical activity of the heart<br>* Other names: EKG, ECG;Procedure: Echocardiogram<br>* A non-invasive sonogram of the heart<br>* Other names: Cardiac echo;Procedure: Blood draw<br>* Blood will be drawn to evaluate general health and renal function (kidney health)<br>* Other names: Blood collection, phlebotomy, lab test;Procedure: Urine collection<br>* Urine will be collection to evaluate renal function (kidney health)<br>Procedure: 2-hour Holter Monitor<br>* A non-invasive test that measures the electrical activity of the heart continuously over 2 hours<br>* Other names: Holter;Other: Brief Pain Inventory questionnaire<br>* A questionnaire about daily pain<br>* Other names: BPI, Pain questionnaire;Other: Quality of Life questionnaire<br>* A questionnaire about the impact of disease on their activities of daily living and quality of life<br>* Other names: SF 36;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| estimated Glomerular Filtration Rate (eGFR) | Change in eGFR since previous participation in study Replagal Enzyme Replacement Therapy for Children With Fabry Disease - NCT00084084 | Study involves one visit only - assessed Baseline Visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left Ventricular Mass Index | LVMI measured in g/m2 by echocardiogram and compared to LVMI results obtained during participation in study Replagal Enzyme Replacement Therapy for Children With Fabry Disease NCT00084084 | Study involves one visit only - assessed Baseline Visit | 
| Heart rate variability assessment | 2 hour holter monitor and compared to holter monitor results obtained during participation in study Replagal Enzyme Replacement Therapy for Children With Fabry Disease NCT00084084 | Study involves one visit only - assessed Baseline Visit | 
| Urine albumin/creatinine ratio | Biomarker of renal function and compared to urine albumin/creatinine ratios obtained during participation in study Replagal Enzyme Replacement Therapy for Children With Fabry Disease NCT00084084 | Study involves one visit only - assessed Baseline Visit | 
| Plasma Lyso-Gb3 | Biomarker of disease and compared to plasma Lyso-Gb3 results obtained during participation in study Replagal Enzyme Replacement Therapy for Children With Fabry Disease NCT00084084 | Study involves one visit only - assessed Baseline Visit | 
| Plasma Gb3 and compared to plasma Gb3 results obtained during participation in study Replagal Enzyme Replacement Therapy for Children With Fabry Disease NCT00084084 | Biomarker of disease | Study involves one visit only - assessed Baseline Visit | 
| Urine Lyso-Gb3 | Biomarker of disease and compared to urine Lyso-Gb3 results obtained during participation in study Replagal Enzyme Replacement Therapy for Children With Fabry Disease NCT00084084 | Study involves one visit only - assessed Baseline Visit | 
| Short-form Brief Pain Inventory (BPI) | Questionnaire designed to assess current level of pain from 0-10. 0 reflects no pain and 10 being the worst possible pain. Results will be compared to pediatric pain assessments obtained during participation in study Replagal Enzyme Replacement Therapy for Children With Fabry Disease NCT00084084 | Study involves one visit only - assessed Baseline Visit | 
| Qualify of Life - Your Health and Well-being | Self-evaluation that describes current physical and emotional health. Questionnaire asks User to rate how Fabry disease impacts User's overall physical and emotional well-being. Questionnaire uses multiple scales to rate User's ability to perform activities of daily life, identify changes in overall health, and identify how changes in physical health and disease has impacted User's emotional well-being. User will be asked to answer multiple questions using the following scales: Poor/Fair/Good/Very good/excellent, Much better than 1 week ago/Somewhat better than 1 week ago/The same as 1 week ago/Somewhat worse than 1 week ago/Much worse than 1 week ago, Limited a lot/Limited a little/Not limited at all, All of the time/Most of the time/Some of the time/A little of the time/None of the time, Not at all/Slightly/Moderately/Quite a bit/Extremely, None/Very mild/Mild/Moderate/Severe/Very severe, Definitely true/Mostly true/Don't know/Mostly false/Definitely false. | Study involves one visit only - assessed Baseline Visit |