ATTR-CMI-CARENCT05776212
Quantitative-imaging in Cardiac Transthyretin Amyloidosis
An observational study of ATTR-CM, run by University of Edinburgh at 1 site in Netherlands.
Trial summary
Transthyretin amyloid cardiomyopathy (ATTR-CM), is a heart muscle disease that's stops the heart muscle working properly. With an ageing population, it is increasingly common but untreated, it has a poor prognosis. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- ATTR-CM
- What is being tested?
- 18F-fluoride PET
- Type of treatment
- Surgery or procedure
- How many people
- 140 participants
- Where
- 1 siteNetherlands
- Study dates
- 25 Aug 2021to 30 Sep 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: * Patients with cardiac transthyretin amyloid * Patients with cardiac light chain amyloid * Patients with hypertrophic cardiomyopathy
Who may be able to join
- Completion of informed consent
- Age > 40 years for patients with ATTR or AL cardiac amyloidosis and age >30 years for patients with HCM
- ATTR cardiac amyloid according to Expert Consensus Recommendations
- AL amyloidosis according to Expert Consensus Recommendations
- Hypertrophic cardiomyopathy according to European Society of Cardiology guidelines
Who cannot join
- Inability or unwilling to give informed consent
- Women who are pregnant, breastfeeding or of child-bearing potential (women who have experienced menarche, are pre-menopausal and have not been sterilised) will not be enrolled into the trial.
- Renal dysfunction (eGFR ≤30 mL/min/1.73m2)
- NYHA Class IV heart failure
- Patients with atrial fibrillation and poor rate control.
- Contraindications to MR
- Previous history of contrast allergy of adverse reactions (gadolinium)
- Contraindications to tafamidis therapy
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
University Medical Centre Groningen
Groningen, 9713 GZ
Riemer HJ Slart, MD PhD, +31 50 361 1835, r.h.j.a.slart@umcg.nl
About this study
Transthyretin amyloid cardiomyopathy (ATTR-CM), is a heart muscle disease that's stops the heart muscle working properly. With an ageing population, it is increasingly common but untreated, it has a poor prognosis. Several novel expensive treatments have become available, although we do not understand exactly how they work and why some patients respond, and others do not. The challenge is to develop better methods for monitoring the effects of these treatments, maximizing their benefits and cost-effectiveness. In I-CARE we aim to bring a new imaging technique, named 18F-fluoride PET, to the clinic and thereby improve the care of patients with ATTR-CM.
Hypotheses:
- A delayed imaging protocol and state-of-the-art PET motion correction will optimise 18F-fluoride imaging in ATTR-CM and provide a clear threshold in myocardial TBR values for the diagnosis of ATTR-CM.
- Optimised 18F-fluoride PET will provide a quantitative marker of the ATTR-CM burden that will allow disease progression and treatment response to be tracked.
- Myocardial 18F-fluoride TBR values will reduce in patients responding to tafamidis treatment and increase in non-responders and patients not receiving therapy
Read the detailed description
Studies have shown that there is calcium deposition in the heart muscle in ATTR-CM but exactly how this happens is not completely understood. Tafamidis, a new drug treatment, has shown improved outcomes for patients with ATTRCM by reducing hospitalisations and improving survival but the mechanism of action of Tafamidis is also not clearly understood yet. 18F-Fluoride PET/CT offers the opportunity to study this phenomenon of calcium deposition in ATTR-CM in more detail and study and track response to the new drug treatment. This will also provide an opportunity to investigate whether tafamidis therapy reduces calcium deposition in the heart muscle associated with ATTR-CM.
We have designed the study specifically to answer our research questions as best as possible, whilst keeping burdens to the patients at a minimum.
To the best of our knowledge this will be the first human study to utilise this imaging technique to assess and track response to the new drug treatment in ATTR-CM. We hope that it will provide major insights in to complex interactions at play, that could drive forward the development of novel therapeutic strategies for patients with ATTR-CM.
- Conditions
- ATTR-CM
- Being tested
- 18F-fluoride PET
- Keywords
- Amyloidosis, Heart failure, 18F-fluoride positron emission tomography (PET), Cardiovascular magnetic resonance (CMR), Tafamidis
- Medical subject headings
- Amyloidosis, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
18F-fluoride PETRadiation
Positron emission tomography using 18F-fluoride as a tracer
| Study group | Role | What they receive |
|---|---|---|
| Work package 1 - Optimisation of 18F-fluoride PET in ATTR-CM | Optimise 18F-fluoride PET imaging of ATTR-CM with increased myocardial tissue to background ratio (TBR) uptake values to provide a state-of-the-art imaging modality for use in the other work packages. (n=15, ATTR-CM subjects) Receives: Radiation: 18F-fluoride PET | |
| Work package 2 - Differentiation ATTR-CM from phenocopies | Establish the optimised 18F-fluoride TBR threshold that best differentiates ATTR-CM (n=100) from phenocopies (subjects with light chain amyloidosis, n=20 and subjects with hypertrophic cardiomyopathy, n=20). Receives: Radiation: 18F-fluoride PET | |
| Work package 3 - In vivo calibration of 18F-fluoride PET | In vivo calibration of 18F-fluoride PET as a marker of the myocardial ATTR burden, calibrating optimised TBR values against the current imaging standard cardiac magnetic resonance imaging extracellular volume. (Subjects with ATTR-CM, n=100) Receives: Radiation: 18F-fluoride PET | |
| Work package 4 - Disease progression and treatment response | Establish ability of 18F-fluoride PET to track disease progression and treatment response in ATTR-CM at one year follow up. (Subjects with ATTR-CM, n=100) Receives: Radiation: 18F-fluoride PET |
What is being measured
The primary outcome is the main question the study is designed to answer.
TBR threshold
Tissue to background ratio with a good specificity and sensitivity to differentiatie subjects with ATTR-CM from subjects with phenocopies.
Measured: 1.5 years
Secondary outcomes (10)
Change in TBR
Change in TBR on 18F-fluoride PET/CT during one year of follow up.
Measured: 2.5 years
Change in cardiac indices on CMR
Change in cardiac indices on magnetic resonance imaging, such as left ventricular ejection fraction
Measured: 2.5 years
Change in cardiac biomarkers
Change in NT-ProBNP during one year of follow up.
Measured: 2.5 years
Change in clinical measures
Change in clinical measures such as 6-minute walk test
Measured: 2.5 years
TBR threshold
Specificity and sensitivity of TBR thresholds at different scanning times.
Measured: 6 months
Change in Cardiac biomarkers
Change in cardiac high sensitivity troponin I during 1 year of follow up
Measured: 2.5 years
Change in clinical measures
Change in KCCQ score during 1 year of follow up
Measured: 2.5 years
Change in cardiac indices on CMR
change in left ventricular mass at 1 year follow up
Measured: 2.5 years
Change in cardiac indices on CMR
change in extracellular volume at 1 year follow up
Measured: 2.5 years
Change in cardiac indices on CMR
Change in left ventricular global longitudinal strain at 1 year follow up
Measured: 2.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2023
- Study start25 Aug 2021
- Primary completion30 Sep 2026 (estimated)
- Study completion30 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ATTR-CMStudies of the same condition, open and under way.
- More trials run by University of EdinburghThe 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 140 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Edinburgh
- Sponsor type
- University, hospital or other
- Collaborators
- British Heart Foundation, Netherlands Heart Foundation, Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)
- Responsible party
- Sponsor
- Investigators
- Marc Dweck, MD PhD, Principal investigator, Centre of Cardiovascular ScienceFabien Siepen, MD PhD, Principal investigator, Heidelberg University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05776212
- Sponsor's protocol ID
- 202000469
- Other IDs
- 2020-003350-72
- Acronym
- I-CARE
- Status last verified
- Jun 2026
- First submitted
- 26 Jan 2023
- Last updated
- 26 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: At the time of publication of the results in a peer-reviewed manuscript, the minimal data set underlying the findings will be made publicly available, either as part of the submission or through a stable, public repository such as EASY (DANS), DataverseNL or Zenodo. The "minimal data set" consists of the data set used to reach the conclusions drawn in the manuscript with related metadata and methods, and any additional data required to replicate the reported study findings in their entirety, including the values behind the means, standard deviations, and other measures reported, the values used to build graphs, and the points extracted from images for analysis. To obtain access to the full data set, a research proposal and analysis plan has to be submitted.
Publications
Tubben A, Prakken NHJ, Ivashchenko OV, Tingen HSA, Glaudemans AWJM, Noordzij W, Nienhuis HLA, van der Meer P, Slart RHJA. Feasibility of the absolute quantification and left ventricular segmentation of cardiac sympathetic innervation in wild-type transthyretin amyloidosis cardiomyopathy with [123I]-MIBG SPECT/CT: The I-NERVE study. J Nucl Cardiol. 2025 Mar;45:102146. doi: 10.1016/j.nuclcard.2025.102146. Epub 2025 Feb 3.
PubMed 39909199
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Quantitative-imaging in Cardiac Transthyretin Amyloidosis
- ClinicalTrials.gov ID
- NCT05776212
- Acronym / sponsor ID
- I-CARE / 202000469
- Conditions
- ATTR-CM
- Keywords
- Amyloidosis, Heart failure, 18F-fluoride positron emission tomography (PET), Cardiovascular magnetic resonance (CMR), Tafamidis
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 140 participants (estimated)
- Lead sponsor
- University of EdinburghUniversity, hospital or other
- Collaborators
- British Heart Foundation, Netherlands Heart Foundation, Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)
- Study start
- 25 Aug 2021 (actual)
- Primary completion
- 30 Sep 2026 (estimated)
- Study completion
- 30 Sep 2026 (estimated)
- First posted
- 20 Mar 2023 (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.
Transthyretin amyloid cardiomyopathy (ATTR-CM), is a heart muscle disease that's stops the heart muscle working properly. With an ageing population, it is increasingly common but untreated, it has a poor prognosis. Several novel expensive treatments have become available, although we do not understand exactly how they work and why some patients respond, and others do not. The challenge is to develop better methods for monitoring the effects of these treatments, maximizing their benefits and cost-effectiveness. In I-CARE we aim to bring a new imaging technique, named 18F-fluoride PET, to the clinic and thereby improve the care of patients with ATTR-CM.
Hypotheses:
- A delayed imaging protocol and state-of-the-art PET motion correction will optimise 18F-fluoride imaging in ATTR-CM and provide a clear threshold in myocardial TBR values for the diagnosis of ATTR-CM.
- Optimised 18F-fluoride PET will provide a quantitative marker of the ATTR-CM burden that will allow disease progression and treatment response to be tracked.
- Myocardial 18F-fluoride TBR values will reduce in patients responding to tafamidis treatment and increase in non-responders and patients not receiving therapy
Detailed description
Studies have shown that there is calcium deposition in the heart muscle in ATTR-CM but exactly how this happens is not completely understood. Tafamidis, a new drug treatment, has shown improved outcomes for patients with ATTRCM by reducing hospitalisations and improving survival but the mechanism of action of Tafamidis is also not clearly understood yet. 18F-Fluoride PET/CT offers the opportunity to study this phenomenon of calcium deposition in ATTR-CM in more detail and study and track response to the new drug treatment. This will also provide an opportunity to investigate whether tafamidis therapy reduces calcium deposition in the heart muscle associated with ATTR-CM.
We have designed the study specifically to answer our research questions as best as possible, whilst keeping burdens to the patients at a minimum.
To the best of our knowledge this will be the first human study to utilise this imaging technique to assess and track response to the new drug treatment in ATTR-CM. We hope that it will provide major insights in to complex interactions at play, that could drive forward the development of novel therapeutic strategies for patients with ATTR-CM.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Work package 1 - Optimisation of 18F-fluoride PET in ATTR-CM | – | Radiation: 18F-fluoride PETOptimise 18F-fluoride PET imaging of ATTR-CM with increased myocardial tissue to background ratio (TBR) uptake values to provide a state-of-the-art imaging modality for use in the other work packages. (n=15, ATTR-CM subjects) |
| Work package 2 - Differentiation ATTR-CM from phenocopies | – | Radiation: 18F-fluoride PETEstablish the optimised 18F-fluoride TBR threshold that best differentiates ATTR-CM (n=100) from phenocopies (subjects with light chain amyloidosis, n=20 and subjects with hypertrophic cardiomyopathy, n=20). |
| Work package 3 - In vivo calibration of 18F-fluoride PET | – | Radiation: 18F-fluoride PETIn vivo calibration of 18F-fluoride PET as a marker of the myocardial ATTR burden, calibrating optimised TBR values against the current imaging standard cardiac magnetic resonance imaging extracellular volume. (Subjects with ATTR-CM, n=100) |
| Work package 4 - Disease progression and treatment response | – | Radiation: 18F-fluoride PETEstablish ability of 18F-fluoride PET to track disease progression and treatment response in ATTR-CM at one year follow up. (Subjects with ATTR-CM, n=100) |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- * Patients with cardiac transthyretin amyloid * Patients with cardiac light chain amyloid * Patients with hypertrophic cardiomyopathy
Key inclusion criteria (5 listed)
- Completion of informed consent
- Age > 40 years for patients with ATTR or AL cardiac amyloidosis and age >30 years for patients with HCM
- ATTR cardiac amyloid according to Expert Consensus Recommendations
- AL amyloidosis according to Expert Consensus Recommendations
- Hypertrophic cardiomyopathy according to European Society of Cardiology guidelines
Key exclusion criteria (8 listed)
- Inability or unwilling to give informed consent
- Women who are pregnant, breastfeeding or of child-bearing potential (women who have experienced menarche, are pre-menopausal and have not been sterilised) will not be enrolled into the trial.
- Renal dysfunction (eGFR ≤30 mL/min/1.73m2)
- NYHA Class IV heart failure
- Patients with atrial fibrillation and poor rate control.
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 |
|---|---|---|
| 18F-fluoride PETPositron emission tomography using 18F-fluoride as a tracer | Radiation | Work package 1 - Optimisation of 18F-fluoride PET in ATTR-CM, Work package 2 - Differentiation ATTR-CM from phenocopies, Work package 3 - In vivo calibration of 18F-fluoride PET, Work package 4 - Disease progression and treatment response |
Primary outcome
TBR threshold
Time frame: 1.5 years
Tissue to background ratio with a good specificity and sensitivity to differentiatie subjects with ATTR-CM from subjects with phenocopies.
10 secondary outcomes
Change in TBR
Time frame: 2.5 years
Change in cardiac indices on CMR
Time frame: 2.5 years
Change in cardiac biomarkers
Time frame: 2.5 years
Change in clinical measures
Time frame: 2.5 years
TBR threshold
Time frame: 6 months
Change in Cardiac biomarkers
Time frame: 2.5 years
Change in clinical measures
Time frame: 2.5 years
Change in cardiac indices on CMR
Time frame: 2.5 years
Change in cardiac indices on CMR
Time frame: 2.5 years
Change in cardiac indices on CMR
Time frame: 2.5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2026.
- Derived from this study: PubMed 39909199Tubben A, Prakken NHJ, Ivashchenko OV, Tingen HSA, Glaudemans AWJM, Noordzij W, Nienhuis HLA, van der Meer P, Slart RHJA. Feasibility of the absolute quantification and left ventricular segmentation of cardiac sympathetic innervation in wild-type transthyretin amyloidosis cardiomyopathy with [123I]-MIBG SPECT/CT: The I-NERVE study. J Nucl Cardiol. 2025 Mar;45:102146. doi: 10.1016/j.nuclcard.2025.102146. Epub 2025 Feb 3.
- Individual participant dataSharing planned: Yes. At the time of publication of the results in a peer-reviewed manuscript, the minimal data set underlying the findings will be made publicly available, either as part of the submission or through a stable, public repository such as EASY (DANS), DataverseNL or Zenodo. The "minimal data set" consists of the data set used to reach the conclusions drawn in the manuscript with related metadata and methods, and any additional data required to replicate the reported study findings in their entirety, including the values behind the means, standard deviations, and other measures reported, the values used to build graphs, and the points extracted from images for analysis. To obtain access to the full data set, a research proposal and analysis plan has to be submitted.
Related trials for ATTR-CM
Active, not recruitingObservational study
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ATTR-CM (Transthyretin Amyloid Cardiomyopathy)
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RecruitingPhase 3
MAGNITUDE: A Phase 3 Study of NTLA-2001 in Participants With Transthyretin Amyloidosis With Cardiomyopathy (ATTR-CM)
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HELIOS-B: A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy
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Not yet recruitingObservational study
Single-arm, Multi-center Study Evaluating the Acceptance and Feasibility of a Digital Remote Monitoring Tool Configured for Patients With ATTR-CM: ACO-Monitor
Transthyretin Amyloid Cardiomyopathy (ATTR-CM)
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.
Marc Dweck, MD PhD principal investigator
Centre of Cardiovascular Science
Fabien Siepen, MD PhD principal investigator
Heidelberg University
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 ATTR-CM, run by University of Edinburgh at 1 site in Netherlands.
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 5 inclusion and 8 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: looking for participants now, as of the sponsor's last update on 26 Jun 2026. 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 Netherlands. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Riemer Slart, MD PhD (+31503611835, r.h.j.a.slart@umcg.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
TBR threshold (time frame: 1.5 years). 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 NCT05776212, which also lists 1 linked publication.
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 26 Jun 2026.