Quantitative-imaging in Cardiac Transthyretin Amyloidosis
I-CARE
2 other identifiers
observational
140
1 country
1
Brief 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. 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:
- 1.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.
- 2.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.
- 3.Myocardial 18F-fluoride TBR values will reduce in patients responding to tafamidis treatment and increase in non-responders and patients not receiving therapy
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for all trials
Started Aug 2021
Longer than P75 for all trials
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
August 25, 2021
CompletedFirst Submitted
Initial submission to the registry
January 26, 2023
CompletedFirst Posted
Study publicly available on registry
March 20, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 30, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
September 30, 2026
June 27, 2025
June 1, 2025
5.1 years
January 26, 2023
June 23, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
TBR threshold
Tissue to background ratio with a good specificity and sensitivity to differentiatie subjects with ATTR-CM from subjects with phenocopies.
1.5 years
Secondary Outcomes (10)
Change in TBR
2.5 years
Change in cardiac indices on CMR
2.5 years
Change in cardiac biomarkers
2.5 years
Change in clinical measures
2.5 years
TBR threshold
6 months
- +5 more secondary outcomes
Study Arms (4)
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)
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).
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)
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)
Interventions
Positron emission tomography using 18F-fluoride as a tracer
Eligibility Criteria
* Patients with cardiac transthyretin amyloid * Patients with cardiac light chain amyloid * Patients with hypertrophic cardiomyopathy
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Edinburghlead
- British Heart Foundationcollaborator
- Netherlands Heart Foundationcollaborator
- Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)collaborator
Study Sites (1)
University Medical Centre Groningen
Groningen, 9713 GZ, Netherlands
Related Publications (1)
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.
PMID: 39909199DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Marc Dweck, MD PhD
Centre of Cardiovascular Science
- PRINCIPAL INVESTIGATOR
Fabien Siepen, MD PhD
Heidelberg University
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- CASE CONTROL
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 26, 2023
First Posted
March 20, 2023
Study Start
August 25, 2021
Primary Completion (Estimated)
September 30, 2026
Study Completion (Estimated)
September 30, 2026
Last Updated
June 27, 2025
Record last verified: 2025-06
Data Sharing
- IPD Sharing
- Will share
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.