Fabry DiseaseNCT02859363
Fabry Disease in Cerebrovascular Disease
An observational study of Fabry Disease, run by Chang Gung Memorial Hospital at 1 site in Taiwan.
Trial summary
Fabry disease is an X-linked disorder of glycosphingolipid catabolism caused by a deficiency of the enzyme α-galactosidase A (α-Gal A), which leads to a progressive accumulation of globotriaosylceramide (Gb-3) in plasma and tissue lysosomes throughout the body. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Fabry Disease
- What is being tested?
- 26 common Fabry mutation types in Taiwan
- How many people
- 700 participants
- Where
- 1 siteTaiwan
- Study dates
- Mar 2016to Aug 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Study population: Historical DNA samples from projects 103-3254C (98-3889A3) and 100-4008C (97-0470B) will perform specific genetic testing.
Who may be able to join
- Age >= 18 y/o
- Both females and males who have ischemic or hemorrhagic stroke before the age of 55 y/o
- Patient or his/her legal representatives are willing to sign the informed consent
Who cannot join
- Ischemic or hemorrhagic stroke patients who are already diagnosed to have Fabry disease
Trial locations and contacts
1 site in 1 country.
Taiwan1 site, 1 recruiting
- Recruiting
Stroke center, Department of Neurology, Linkou Chang Gung Memorial Hospital
Kweishan, Taoyuan, 333
Tsong-Hai Lee, MD, PhD, +886-3-3281200 ext. 8340, thlee@adm.cgmh.org.tw
Tsong-Hai Lee, MD, PhD
About this study
Official title: Improving the Diagnostic Rate of Fabry Disease in Patients With Cerebrovascular Involvement in Taiwan- a Cohort Screening Program
Fabry disease is an X-linked disorder of glycosphingolipid catabolism caused by a deficiency of the enzyme α-galactosidase A (α-Gal A), which leads to a progressive accumulation of globotriaosylceramide (Gb-3) in plasma and tissue lysosomes throughout the body. Lysosomal accumulation can result in lysosomal and cellular dysfunction, which leads to renal, cardiac, and central nervous system (CNS) complications.
It is estimated that 1 in 40,000 males has Fabry disease, whereas the estimated prevalence in the general population is 1 in 117,000 people. Newborn screenings for both classical and atypical Fabry disease in Taiwan also revealed a markedly high incidence of 1 in 2,300 and 1 in 3,000 newborns. Cerebrovascular variant Fabry disease may affect up to 4.9% of male patients and 2.4% of female patients with idiopathic stroke.
The diagnosis of Fabry disease can be challenging due to the diverse signs and symptoms, different ages of onset, and variable timing and severity of progression. The importance of Fabry disease lies in the irreversible renal, cardiac, cerebrovascular, and neurological damage. An early diagnosis of Fabry disease is important for initiating symptom management and reducing life-threatening complications, as well as for early identification of other affected family members. Therefore, the present study would like to conduct further screening of high-risk group of early cerebrovascular involvement that is essential for the successful management of Fabry disease.
Read the detailed description
This is a cross-sectional, population-based study to identify Fabry disease in patients with early cerebrovascular involvement. Eligible patients are age above 18 years old (<=55 years old) with early cerebrovascular involvement and have provided inform consent. Patients who have been diagnosed Fabry disease are not eligible.
The present study will use samples of early cerebrovascular involvement patients which have been enrolled in two previous IRB approved projects [103-3254C (origin 98-3889A3), 100-4008C (origin 97-0470B)], participants of both studies have consented that participants' samples could be further investigated if needed.
Since, the investigators cannot ensure whether the condition of enzyme activity of frozen plasma sample were decayed after long-term storage and the investigators don't have available normal range of enzyme activity of historical plasma sample, the investigators will perform specific genotyping of Fabry disease for these patients according to the specific mutation variants which have been identified in Taiwan population previously.
Patients will be recalled to assess Fabry related symptoms if genetic testing has mutation finding and family screening will be performed if applicable. Further inform consent will be obtained as well.
- Conditions
- Fabry Disease
- Being tested
- 26 common Fabry mutation types in Taiwan
- Medical subject headings
- Fabry Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
26 common Fabry mutation types in TaiwanGenetic
Historical DNA samples from projects 103-3254C (98-3889A3) and 100-4008C (97-0470B) will perform specific genetic testing.
| Study group | Role | What they receive |
|---|---|---|
| Young stroke | Historical DNA samples from projects 103-3254C (98-3889A3) and 100-4008C (97-0470B) will perform specific genetic testing for the 26 common Fabry mutation types in Taiwan. Receives: Genetic: 26 common Fabry mutation types in Taiwan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Conclusive diagnosis of Fabry disease
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2016 (estimated)
- Study startMar 2016
- Primary completionMar 2017 (estimated)
- Study completionAug 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Fabry DiseaseStudies of the same condition, open and under way.
- More trials run by Chang Gung Memorial HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 700 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chang Gung Memorial Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Sanofi
- Responsible party
- Principal investigator, Tsong-Hai Lee, Chang Gung Memorial Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02859363
- Sponsor's protocol ID
- Fabry Ver. 2_20160301_CGMH-LK
- Status last verified
- Aug 2016
- First submitted
- 4 Aug 2016
- Last updated
- 10 Aug 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Branton MH, Schiffmann R, Sabnis SG, Murray GJ, Quirk JM, Altarescu G, Goldfarb L, Brady RO, Balow JE, Austin Iii HA, Kopp JB. Natural history of Fabry renal disease: influence of alpha-galactosidase A activity and genetic mutations on clinical course. Medicine (Baltimore). 2002 Mar;81(2):122-38. doi: 10.1097/00005792-200203000-00003. No abstract available.
PubMed 11889412Kampmann C, Linhart A, Baehner F, Palecek T, Wiethoff CM, Miebach E, Whybra C, Gal A, Bultas J, Beck M. Onset and progression of the Anderson-Fabry disease related cardiomyopathy. Int J Cardiol. 2008 Nov 28;130(3):367-73. doi: 10.1016/j.ijcard.2008.03.007. Epub 2008 Jun 24.
PubMed 18572264Rolfs A, Bottcher T, Zschiesche M, Morris P, Winchester B, Bauer P, Walter U, Mix E, Lohr M, Harzer K, Strauss U, Pahnke J, Grossmann A, Benecke R. Prevalence of Fabry disease in patients with cryptogenic stroke: a prospective study. Lancet. 2005 Nov 19;366(9499):1794-6. doi: 10.1016/S0140-6736(05)67635-0.
PubMed 16298216Meikle PJ, Hopwood JJ, Clague AE, Carey WF. Prevalence of lysosomal storage disorders. JAMA. 1999 Jan 20;281(3):249-54. doi: 10.1001/jama.281.3.249.
PubMed 9918480Hwu WL, Chien YH, Lee NC, Chiang SC, Dobrovolny R, Huang AC, Yeh HY, Chao MC, Lin SJ, Kitagawa T, Desnick RJ, Hsu LW. Newborn screening for Fabry disease in Taiwan reveals a high incidence of the later-onset GLA mutation c.936+919G>A (IVS4+919G>A). Hum Mutat. 2009 Oct;30(10):1397-405. doi: 10.1002/humu.21074.
PubMed 19621417Liao HC, Chiang CC, Niu DM, Wang CH, Kao SM, Tsai FJ, Huang YH, Liu HC, Huang CK, Gao HJ, Yang CF, Chan MJ, Lin WD, Chen YJ. Detecting multiple lysosomal storage diseases by tandem mass spectrometry--a national newborn screening program in Taiwan. Clin Chim Acta. 2014 Apr 20;431:80-6. doi: 10.1016/j.cca.2014.01.030. Epub 2014 Feb 7.
PubMed 24513544Ries M, Ramaswami U, Parini R, Lindblad B, Whybra C, Willers I, Gal A, Beck M. The early clinical phenotype of Fabry disease: a study on 35 European children and adolescents. Eur J Pediatr. 2003 Nov;162(11):767-72. doi: 10.1007/s00431-003-1299-3. Epub 2003 Sep 20.
PubMed 14505049Mehta A, Ricci R, Widmer U, Dehout F, Garcia de Lorenzo A, Kampmann C, Linhart A, Sunder-Plassmann G, Ries M, Beck M. Fabry disease defined: baseline clinical manifestations of 366 patients in the Fabry Outcome Survey. Eur J Clin Invest. 2004 Mar;34(3):236-42. doi: 10.1111/j.1365-2362.2004.01309.x.
PubMed 15025684Lee SH, Li CF, Lin HY, Lin CH, Liu HC, Tsai SF, Niu DM. High-throughput detection of common sequence variations of Fabry disease in Taiwan using DNA mass spectrometry. Mol Genet Metab. 2014 Apr;111(4):507-12. doi: 10.1016/j.ymgme.2014.02.004. Epub 2014 Feb 17.
PubMed 24613481
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Improving the Diagnostic Rate of Fabry Disease in Patients With Cerebrovascular Involvement in Taiwan- a Cohort Screening Program
- ClinicalTrials.gov ID
- NCT02859363
- Acronym / sponsor ID
- Fabry Ver. 2_20160301_CGMH-LK
- Conditions
- Fabry Disease
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 700 participants (estimated)
- Lead sponsor
- Chang Gung Memorial HospitalUniversity, hospital or other
- Collaborators
- Sanofi
- Study start
- Mar 2016
- Primary completion
- Mar 2017 (estimated)
- Study completion
- Aug 2017 (estimated)
- First posted
- 9 Aug 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Fabry disease is an X-linked disorder of glycosphingolipid catabolism caused by a deficiency of the enzyme α-galactosidase A (α-Gal A), which leads to a progressive accumulation of globotriaosylceramide (Gb-3) in plasma and tissue lysosomes throughout the body. Lysosomal accumulation can result in lysosomal and cellular dysfunction, which leads to renal, cardiac, and central nervous system (CNS) complications.
It is estimated that 1 in 40,000 males has Fabry disease, whereas the estimated prevalence in the general population is 1 in 117,000 people. Newborn screenings for both classical and atypical Fabry disease in Taiwan also revealed a markedly high incidence of 1 in 2,300 and 1 in 3,000 newborns. Cerebrovascular variant Fabry disease may affect up to 4.9% of male patients and 2.4% of female patients with idiopathic stroke.
The diagnosis of Fabry disease can be challenging due to the diverse signs and symptoms, different ages of onset, and variable timing and severity of progression. The importance of Fabry disease lies in the irreversible renal, cardiac, cerebrovascular, and neurological damage. An early diagnosis of Fabry disease is important for initiating symptom management and reducing life-threatening complications, as well as for early identification of other affected family members. Therefore, the present study would like to conduct further screening of high-risk group of early cerebrovascular involvement that is essential for the successful management of Fabry disease.
Detailed description
This is a cross-sectional, population-based study to identify Fabry disease in patients with early cerebrovascular involvement. Eligible patients are age above 18 years old (<=55 years old) with early cerebrovascular involvement and have provided inform consent. Patients who have been diagnosed Fabry disease are not eligible.
The present study will use samples of early cerebrovascular involvement patients which have been enrolled in two previous IRB approved projects [103-3254C (origin 98-3889A3), 100-4008C (origin 97-0470B)], participants of both studies have consented that participants' samples could be further investigated if needed.
Since, the investigators cannot ensure whether the condition of enzyme activity of frozen plasma sample were decayed after long-term storage and the investigators don't have available normal range of enzyme activity of historical plasma sample, the investigators will perform specific genotyping of Fabry disease for these patients according to the specific mutation variants which have been identified in Taiwan population previously.
Patients will be recalled to assess Fabry related symptoms if genetic testing has mutation finding and family screening will be performed if applicable. Further inform consent will be obtained as well.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Young stroke | – | Genetic: 26 common Fabry mutation types in TaiwanHistorical DNA samples from projects 103-3254C (98-3889A3) and 100-4008C (97-0470B) will perform specific genetic testing for the 26 common Fabry mutation types in Taiwan. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- Historical DNA samples from projects 103-3254C (98-3889A3) and 100-4008C (97-0470B) will perform specific genetic testing.
Key inclusion criteria (3 listed)
- Age >= 18 y/o
- Both females and males who have ischemic or hemorrhagic stroke before the age of 55 y/o
- Patient or his/her legal representatives are willing to sign the informed consent
Key exclusion criteria (1 listed)
- Ischemic or hemorrhagic stroke patients who are already diagnosed to have Fabry disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 26 common Fabry mutation types in TaiwanHistorical DNA samples from projects 103-3254C (98-3889A3) and 100-4008C (97-0470B) will perform specific genetic testing. | Genetic | Young stroke |
Primary outcome
Conclusive diagnosis of Fabry disease
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2016.
- Background: PubMed 11889412Branton MH, Schiffmann R, Sabnis SG, Murray GJ, Quirk JM, Altarescu G, Goldfarb L, Brady RO, Balow JE, Austin Iii HA, Kopp JB. Natural history of Fabry renal disease: influence of alpha-galactosidase A activity and genetic mutations on clinical course. Medicine (Baltimore). 2002 Mar;81(2):122-38. doi: 10.1097/00005792-200203000-00003. No abstract available.
- Background: PubMed 18572264Kampmann C, Linhart A, Baehner F, Palecek T, Wiethoff CM, Miebach E, Whybra C, Gal A, Bultas J, Beck M. Onset and progression of the Anderson-Fabry disease related cardiomyopathy. Int J Cardiol. 2008 Nov 28;130(3):367-73. doi: 10.1016/j.ijcard.2008.03.007. Epub 2008 Jun 24.
- Background: PubMed 16298216Rolfs A, Bottcher T, Zschiesche M, Morris P, Winchester B, Bauer P, Walter U, Mix E, Lohr M, Harzer K, Strauss U, Pahnke J, Grossmann A, Benecke R. Prevalence of Fabry disease in patients with cryptogenic stroke: a prospective study. Lancet. 2005 Nov 19;366(9499):1794-6. doi: 10.1016/S0140-6736(05)67635-0.
- Background: PubMed 9918480Meikle PJ, Hopwood JJ, Clague AE, Carey WF. Prevalence of lysosomal storage disorders. JAMA. 1999 Jan 20;281(3):249-54. doi: 10.1001/jama.281.3.249.
- Background: PubMed 19621417Hwu WL, Chien YH, Lee NC, Chiang SC, Dobrovolny R, Huang AC, Yeh HY, Chao MC, Lin SJ, Kitagawa T, Desnick RJ, Hsu LW. Newborn screening for Fabry disease in Taiwan reveals a high incidence of the later-onset GLA mutation c.936+919G>A (IVS4+919G>A). Hum Mutat. 2009 Oct;30(10):1397-405. doi: 10.1002/humu.21074.
- Background: PubMed 24513544Liao HC, Chiang CC, Niu DM, Wang CH, Kao SM, Tsai FJ, Huang YH, Liu HC, Huang CK, Gao HJ, Yang CF, Chan MJ, Lin WD, Chen YJ. Detecting multiple lysosomal storage diseases by tandem mass spectrometry--a national newborn screening program in Taiwan. Clin Chim Acta. 2014 Apr 20;431:80-6. doi: 10.1016/j.cca.2014.01.030. Epub 2014 Feb 7.
- Background: PubMed 14505049Ries M, Ramaswami U, Parini R, Lindblad B, Whybra C, Willers I, Gal A, Beck M. The early clinical phenotype of Fabry disease: a study on 35 European children and adolescents. Eur J Pediatr. 2003 Nov;162(11):767-72. doi: 10.1007/s00431-003-1299-3. Epub 2003 Sep 20.
- Background: PubMed 15025684Mehta A, Ricci R, Widmer U, Dehout F, Garcia de Lorenzo A, Kampmann C, Linhart A, Sunder-Plassmann G, Ries M, Beck M. Fabry disease defined: baseline clinical manifestations of 366 patients in the Fabry Outcome Survey. Eur J Clin Invest. 2004 Mar;34(3):236-42. doi: 10.1111/j.1365-2362.2004.01309.x.
- Background: PubMed 24613481Lee SH, Li CF, Lin HY, Lin CH, Liu HC, Tsai SF, Niu DM. High-throughput detection of common sequence variations of Fabry disease in Taiwan using DNA mass spectrometry. Mol Genet Metab. 2014 Apr;111(4):507-12. doi: 10.1016/j.ymgme.2014.02.004. Epub 2014 Feb 17.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Fabry Disease, run by Chang Gung Memorial Hospital at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Tsong-Hai Lee, MD, PhD (+886-3-3281200 ext. 8340, thlee@adm.cgmh.org.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Conclusive diagnosis of Fabry disease (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02859363, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Aug 2016.