Fabry Disease, Cardiac VariantNCT06226987
Molecular Imaging in Fabry Disease of the Heart
An observational study of Fabry Disease, Cardiac Variant, run by University of Cambridge at 1 site in United Kingdom.
Trial summary
Better methods for early detection of cardiac involvement in Fabry disease are needed to inform clinical management decisions that can help prevent or slow the progression of cardiac complications. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Fabry Disease, Cardiac Variant
- What is being tested?
- 68Ga-DOTATATE PET/MRI
- How many people
- 12 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 2 Jan 2024to 2 Jan 2026
- 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 years and older
- All sexes
- Adult, Older adult
Study population: Participants with cardiac involvement in Fabry disease assessed by MRI
Who may be able to join
- Male or female participants >18 years old
- Able to give written, informed consent and to lie flat
- Have Fabry disease based on molecular diagnosis (at a minimum, documented enzyme deficiency in males and documented pathogenic mutation in females)
- Cardiac MRI within 3 years documenting cardiac involvement in Fabry disease (left ventricular hypertrophy and/or late gadolinium enhancement and/or myocardial oedema)
Who cannot join
- Any other diagnosis associated with cardiac muscle inflammation, including myocarditis
- Previous gene therapy
- Contra-indication to MRI scanning or intravenous gadolinium contrast (prior contrast reaction or chronic kidney disease with eGFR <30 mL/min/1.73 m2)
- Women of child bearing potential not using adequate contraception
- Uncontrolled atrial fibrillation
- Any medical condition, in the opinion of the investigator, that prevents the participant from lying flat during scanning, or from participating in the study
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Cambridge University Hospital NHS Foundation Trust
Cambridge, Cambridgeshire, CB2 0QQ
Patrick Deegan, MD
About this study
Better methods for early detection of cardiac involvement in Fabry disease are needed to inform clinical management decisions that can help prevent or slow the progression of cardiac complications. In the Molecular Imaging of Inflammation in Fabry Disease of the Heart study, the investigators will test the use of 68Ga-DOTATATE PET/MRI for identifying myocardial inflammation in patients with Fabry disease.
Read the detailed description
Fabry disease (OMIM 30150) is caused by mutations in the gene (AGAL) encoding for the lysosomal enzyme α-galactosidase A. Diminished activity of this enzyme results in progressive accumulation of its substrate globotriaosylceramide (Gb3) in the lysosomes of various cell types, including vascular endothelial cells, cardiomyocytes, valvular fibrocytes, conduction cells. The involvement of the heart in Fabry disease results in rhythm disturbances, progressive hypertrophy and scarring of the left ventricle leading to diastolic and systolic dysfunction.
Conventional diagnostic methods such as electrocardiography, transthoracic echocardiography and even magnetic resonance imaging (MRI) are not sensitive enough to detect early damage to myocardial tissue in Fabry disease. Identifying subtle early changes, at a point when specific treatment may be optimized, is therefore an area of ongoing interest. Early perspectives on Fabry heart involvement concentrated on the left ventricular hypertrophy. Later the widespread use of Cardiac MRI introduced the role of fibrosis, as suggested by the appearance of late gadolinium enhancement (LGE) in characteristic areas of the myocardium. Most recently, detection of oedema by T2-weighted imaging and/or T2-mapping on MRI, as well as 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) scanning have pointed to the possibility of focal inflammation as a causative factor in progression of the myocardial disease to replacement fibrosis, with its attendant risk of fatal arrhythmia and cardiac decompensation. Whether the oedema signal on MRI sequences truly represents tissue inflammation in Fabry disease and whether LGE fully corresponds to replacement fibrosis remains unknown. Circulating markers of inflammation and immune activation are elevated in Fabry cardiomyopathy, but no fully specific marker has yet been found to correspond to either myocardial focal oedema or LGE.
Although MRI is important for diagnosis and risk stratification in patients with cardiac involvement in Fabry disease, findings such as LGE, myocardial oedema and native T1 mapping tell the clinician little that is specific about the underlying disease mechanisms. Moreover, early inflammatory changes may occur in Fabry disease before the manifestation of such abnormalities are detectable by MRI. By combining PET imaging of myocardial inflammation with detailed MRI assessments of cardiac function, structure and tissue characterisation, hybrid PET/MRI has the potential to offer a comprehensive non-invasive workup for patients with Fabry disease.
Previous work has shown that 68Ga-DOTA-(Tyr3)-octreotate (DOTATATE), a somatostatin receptor PET tracer used in oncology imaging, can be re-purposed to image inflammation in the cardiovascular system. This method could be of particular use in conditions associated with focal myocardial inflammation such as Fabry disease because of low physiological expression of somatostatin receptors in healthy heart muscle, and therefore low background PET signal. Here, the investigators will investigate the use of 68Ga-DOTATATE PET/MRI for identifying myocardial inflammation in patients with Fabry disease.
- Conditions
- Fabry Disease, Cardiac Variant
- Being tested
- 68Ga-DOTATATE PET/MRI
- Medical subject headings
- Fabry Disease, Cardiac Variant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
68Ga-DOTATATE PET/MRIDiagnostic test
PET/MRI scanning
| Study group | Role | What they receive |
|---|---|---|
| Fabry Disease with cardiac involvement | Not described Receives: Diagnostic Test: 68Ga-DOTATATE PET/MRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
PET imaging vs. oedema detected by MRI
Concordance between 68Ga-DOTATATE PET signal and myocardial oedema on MRI assessed by T2-weighted imaging
Measured: Baseline
PET imaging vs. fibrosis detected by MRI
Concordance between 68Ga-DOTATATE PET signal and myocardial fibrosis detected by late gadolinium enhancement MRI
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2024
- Study start2 Jan 2024
- Primary completion2 Jan 2026 (estimated)
- Study completion2 Jan 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Fabry Disease, Cardiac VariantStudies of the same condition, open and under way.
- 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
- Prospective
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Cambridge
- Sponsor type
- University, hospital or other
- Collaborators
- Sanofi
- Responsible party
- Principal investigator, Jason Tarkin, University of Cambridge
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06226987
- Sponsor's protocol ID
- A095007
- Status last verified
- Jul 2024
- First submitted
- 17 Jan 2024
- Last updated
- 22 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Tarkin JM, Joshi FR, Evans NR, Chowdhury MM, Figg NL, Shah AV, Starks LT, Martin-Garrido A, Manavaki R, Yu E, Kuc RE, Grassi L, Kreuzhuber R, Kostadima MA, Frontini M, Kirkpatrick PJ, Coughlin PA, Gopalan D, Fryer TD, Buscombe JR, Groves AM, Ouwehand WH, Bennett MR, Warburton EA, Davenport AP, Rudd JH. Detection of Atherosclerotic Inflammation by 68Ga-DOTATATE PET Compared to [18F]FDG PET Imaging. J Am Coll Cardiol. 2017 Apr 11;69(14):1774-1791. doi: 10.1016/j.jacc.2017.01.060.
PubMed 28385306Corovic A, Wall C, Nus M, Gopalan D, Huang Y, Imaz M, Zulcinski M, Peverelli M, Uryga A, Lambert J, Bressan D, Maughan RT, Pericleous C, Dubash S, Jordan N, Jayne DR, Hoole SP, Calvert PA, Dean AF, Rassl D, Barwick T, Iles M, Frontini M, Hannon G, Manavaki R, Fryer TD, Aloj L, Graves MJ, Gilbert FJ, Dweck MR, Newby DE, Fayad ZA, Reynolds G, Morgan AW, Aboagye EO, Davenport AP, Jorgensen HF, Mallat Z, Bennett MR, Peters JE, Rudd JHF, Mason JC, Tarkin JM. Somatostatin Receptor PET/MR Imaging of Inflammation in Patients With Large Vessel Vasculitis and Atherosclerosis. J Am Coll Cardiol. 2023 Jan 31;81(4):336-354. doi: 10.1016/j.jacc.2022.10.034.
PubMed 36697134
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Molecular Imaging in Fabry Disease of the Heart
- ClinicalTrials.gov ID
- NCT06226987
- Acronym / sponsor ID
- A095007
- Conditions
- Fabry Disease, Cardiac Variant
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- University of CambridgeUniversity, hospital or other
- Collaborators
- Sanofi
- Study start
- 2 Jan 2024 (actual)
- Primary completion
- 2 Jan 2026 (estimated)
- Study completion
- 2 Jan 2026 (estimated)
- First posted
- 26 Jan 2024 (actual)
- 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.
Better methods for early detection of cardiac involvement in Fabry disease are needed to inform clinical management decisions that can help prevent or slow the progression of cardiac complications. In the Molecular Imaging of Inflammation in Fabry Disease of the Heart study, the investigators will test the use of 68Ga-DOTATATE PET/MRI for identifying myocardial inflammation in patients with Fabry disease.
Detailed description
Fabry disease (OMIM 30150) is caused by mutations in the gene (AGAL) encoding for the lysosomal enzyme α-galactosidase A. Diminished activity of this enzyme results in progressive accumulation of its substrate globotriaosylceramide (Gb3) in the lysosomes of various cell types, including vascular endothelial cells, cardiomyocytes, valvular fibrocytes, conduction cells. The involvement of the heart in Fabry disease results in rhythm disturbances, progressive hypertrophy and scarring of the left ventricle leading to diastolic and systolic dysfunction.
Conventional diagnostic methods such as electrocardiography, transthoracic echocardiography and even magnetic resonance imaging (MRI) are not sensitive enough to detect early damage to myocardial tissue in Fabry disease. Identifying subtle early changes, at a point when specific treatment may be optimized, is therefore an area of ongoing interest. Early perspectives on Fabry heart involvement concentrated on the left ventricular hypertrophy. Later the widespread use of Cardiac MRI introduced the role of fibrosis, as suggested by the appearance of late gadolinium enhancement (LGE) in characteristic areas of the myocardium. Most recently, detection of oedema by T2-weighted imaging and/or T2-mapping on MRI, as well as 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) scanning have pointed to the possibility of focal inflammation as a causative factor in progression of the myocardial disease to replacement fibrosis, with its attendant risk of fatal arrhythmia and cardiac decompensation. Whether the oedema signal on MRI sequences truly represents tissue inflammation in Fabry disease and whether LGE fully corresponds to replacement fibrosis remains unknown. Circulating markers of inflammation and immune activation are elevated in Fabry cardiomyopathy, but no fully specific marker has yet been found to correspond to either myocardial focal oedema or LGE.
Although MRI is important for diagnosis and risk stratification in patients with cardiac involvement in Fabry disease, findings such as LGE, myocardial oedema and native T1 mapping tell the clinician little that is specific about the underlying disease mechanisms. Moreover, early inflammatory changes may occur in Fabry disease before the manifestation of such abnormalities are detectable by MRI. By combining PET imaging of myocardial inflammation with detailed MRI assessments of cardiac function, structure and tissue characterisation, hybrid PET/MRI has the potential to offer a comprehensive non-invasive workup for patients with Fabry disease.
Previous work has shown that 68Ga-DOTA-(Tyr3)-octreotate (DOTATATE), a somatostatin receptor PET tracer used in oncology imaging, can be re-purposed to image inflammation in the cardiovascular system. This method could be of particular use in conditions associated with focal myocardial inflammation such as Fabry disease because of low physiological expression of somatostatin receptors in healthy heart muscle, and therefore low background PET signal. Here, the investigators will investigate the use of 68Ga-DOTATATE PET/MRI for identifying myocardial inflammation in patients with Fabry disease.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Fabry Disease with cardiac involvement | – | Diagnostic Test: 68Ga-DOTATATE PET/MRI |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- Participants with cardiac involvement in Fabry disease assessed by MRI
Key inclusion criteria (4 listed)
- Male or female participants >18 years old
- Able to give written, informed consent and to lie flat
- Have Fabry disease based on molecular diagnosis (at a minimum, documented enzyme deficiency in males and documented pathogenic mutation in females)
- Cardiac MRI within 3 years documenting cardiac involvement in Fabry disease (left ventricular hypertrophy and/or late gadolinium enhancement and/or myocardial oedema)
Key exclusion criteria (6 listed)
- Any other diagnosis associated with cardiac muscle inflammation, including myocarditis
- Previous gene therapy
- Contra-indication to MRI scanning or intravenous gadolinium contrast (prior contrast reaction or chronic kidney disease with eGFR <30 mL/min/1.73 m2)
- Women of child bearing potential not using adequate contraception
- Uncontrolled atrial fibrillation
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 |
|---|---|---|
| 68Ga-DOTATATE PET/MRIPET/MRI scanning | Diagnostic test | Fabry Disease with cardiac involvement |
Primary outcome
PET imaging vs. oedema detected by MRI
Time frame: Baseline
Concordance between 68Ga-DOTATATE PET signal and myocardial oedema on MRI assessed by T2-weighted imaging
PET imaging vs. fibrosis detected by MRI
Time frame: Baseline
Concordance between 68Ga-DOTATATE PET signal and myocardial fibrosis detected by late gadolinium enhancement MRI
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2024.
- Results publication: PubMed 28385306Tarkin JM, Joshi FR, Evans NR, Chowdhury MM, Figg NL, Shah AV, Starks LT, Martin-Garrido A, Manavaki R, Yu E, Kuc RE, Grassi L, Kreuzhuber R, Kostadima MA, Frontini M, Kirkpatrick PJ, Coughlin PA, Gopalan D, Fryer TD, Buscombe JR, Groves AM, Ouwehand WH, Bennett MR, Warburton EA, Davenport AP, Rudd JH. Detection of Atherosclerotic Inflammation by 68Ga-DOTATATE PET Compared to [18F]FDG PET Imaging. J Am Coll Cardiol. 2017 Apr 11;69(14):1774-1791. doi: 10.1016/j.jacc.2017.01.060.
- Results publication: PubMed 36697134Corovic A, Wall C, Nus M, Gopalan D, Huang Y, Imaz M, Zulcinski M, Peverelli M, Uryga A, Lambert J, Bressan D, Maughan RT, Pericleous C, Dubash S, Jordan N, Jayne DR, Hoole SP, Calvert PA, Dean AF, Rassl D, Barwick T, Iles M, Frontini M, Hannon G, Manavaki R, Fryer TD, Aloj L, Graves MJ, Gilbert FJ, Dweck MR, Newby DE, Fayad ZA, Reynolds G, Morgan AW, Aboagye EO, Davenport AP, Jorgensen HF, Mallat Z, Bennett MR, Peters JE, Rudd JHF, Mason JC, Tarkin JM. Somatostatin Receptor PET/MR Imaging of Inflammation in Patients With Large Vessel Vasculitis and Atherosclerosis. J Am Coll Cardiol. 2023 Jan 31;81(4):336-354. doi: 10.1016/j.jacc.2022.10.034.
- 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, Cardiac Variant, run by University of Cambridge at 1 site in United Kingdom.
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 4 inclusion and 6 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 22 Jul 2024. 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 United Kingdom. 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 Jason M Tarkin, PhD MBBS (+44(0)1223331504, jt545@cam.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PET imaging vs. oedema detected by MRI (time frame: Baseline). The study lists 2 primary outcomes in all. 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 NCT06226987, which also lists 2 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 22 Jul 2024.