AmyloidosisNCT05010980
Early Detection of Cardiac Amyloidosis
An observational study of Amyloidosis and Aortic Valve Stenosis, run by Heinrich-Heine University, Duesseldorf at 1 site in Germany.
Trial summary
Due to a lack of therapeutic options, the diagnosis of cardiac (wt)-ATTR amyloidosis was for a long time overshadowed by other diseases and therefore was or still is often diagnosed with considerable delay. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Amyloidosis, Aortic Valve Stenosis
- What is being tested?
- CMR and scintigraphy
- How many people
- 400 participants
- Where
- 1 siteGermany
- Study dates
- 1 Aug 2021to Sep 2023
- 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 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Study population: patients undergoing a routine echocardiographic assessment which results in the clinical indication for CMR and scintigraphy among patients with aortic valve stenosis
Who may be able to join
- Age > 65 years
- Patients who fulfill at least 3 of the following 4 criteria based on cardiac ultrasound examination, which results in the clinical indication for CMR and scintigraphy
- Evidence an aortic valve stenosis, defined as opening area according to velocity time integral (VTI) < 2cm2
- Hypertrophy of the interventricular septum (IVS) > 11mm
- Echocardiographically assesed reduced stroke volume index (SVI) (< 35 ml/m2)
- Reduced ratio of electrical signals of the heart (in the ECG) to the mass of the heart muscle (< 1.6 *10-2 mV/g/m2)
Who cannot join
- Patients who are incapable of giving consent,
- Age < 65 years
- patients who have not given their written consent
Trial locations and contacts
1 site in 1 country.
Germany1 site, 1 recruiting
- Recruiting
Division of Cardiology, Pulmonary Diseases and Vascular Medicine
Düsseldorf, 40225
Ralf Westenfeld, MD, 00492118118800, ctu@med.uni-duesseldorf.de
Ralf Westenfeld, MD
About this study
Official title: Early Detection of Cardiac Amyloidosis Among Patients With Aortic Valve Stenosis.
Due to a lack of therapeutic options, the diagnosis of cardiac (wt)-ATTR amyloidosis was for a long time overshadowed by other diseases and therefore was or still is often diagnosed with considerable delay.
The aim of the study is to estimate the prevalence of cardiac amyloidosis among patients with mild-to-moderate aortic valve stenosis (AS).
Besides that a screening algorithm based on echocardiographic parameters will be developed, to facilitate the early detection of cardiac amyloidosis.
Read the detailed description
Due to a lack of therapeutic options, the diagnosis of cardiac (wt)-ATTR amyloidosis was for a long time overshadowed by other diseases and therefore was or still is often diagnosed with considerable delay. On the one hand, it was assumed that the number of cases was significantly lower than the latest studies showed, and on the other hand, until the introduction of new therapeutic agents, there was no approved therapeutic option available, so that the corresponding diagnosis did not result in any therapeutic consequences.
This has changed fundamentally in recent years. For example, analyses of patients who underwent interventional aortic valve replacement (TAVI) as a result of high-grade AS demonstrated cardiac amyloidosis in up to 16% of these patients. Patients with (paradoxical) low flow low gradient (lflg) AS, which is echocardiographically characterized by a low stroke volume index (SVI), are particularly frequently affected. In light of these data, recent publications recommend the use of a low SVI, in conjunction with ECG criteria (low Sokolow-Lyon index) relative to echocardiographically determined left ventricular myocardial mass (SLI/ LVM) as a screening tool for the presence of amyloidosis in the patient population with high-grade aortic valve stenosis.
In patients with mild-to-moderate AS, the prevalence of amyloidosis and the validity of these methods has not yet been clarified. However, identification of these would be, of particular interest, especially in view of the new therapy options, since with the modern therapy methods can only improve prognosis if the diagnosis is made early.
When cardiac amyloidosis is suspected, three procedures are currently used in clinical practice
- myocardial biopsy (BX)
- cardiac MRI (CMR)
- scintigraphy with 99mTc phosphates as tracer (scintigraphy)
Myocardial biopsy is not suitable as a broad screening method due to cost, effort, and limited feasibility at designated centers. It's rather a goldstandard for confirming nonconclusive findings or for further differential diagnosis or prognostic assessment.
Scintigraphy and CMR are the established and regularly used methods for the detection of cardiac amyloidosis.
Scintigraphy is a cost-effective examination that can be performed on an outpatient basis with low radiation exposure and high sensitivity and specificity for the detection of cardiac (ATTR) amyloidosis, especially in (still) asymptomatic patients. Scintigraphy is already recommended for the screening of ATTR amyloidosis. Besides scintigraphy, the CMR also offers good sensitivity (80%) and specificity (94%) for the diagnosis of cardiac amyloidosis, CMR also offers the advantage of a comprehensive cardiac differential diagnosis with possible exclusion of amyloidosis. It can also be performed on an outpatient basis, does not require a radiation-based procedure and can diagnose cardiac amyloidosis with high reproducibility, both with and without contrast medium. Which of the latter two examinations is more suitable for amyloidosis screening has not been conclusively determined. Although CMR and scintigraphy are regulary used for amyloidosis screening, it is not yet known, which of the two examinations is more suitable.
The aim of the study is to estimate the prevalence of cardiac amyloidosis in mild-to-moderate AS.
Furthermore, a screening algorithm based on echocardiographic parameters should be developed, to facilitate the early detection of cardiac amyloidosis: This would allow earlier initiation of therapy and thus better therapeutic success in patients with cardiac amyloidosis. Accordingly, a better quality of life as well as a prolonged survival of these severely affected patients could be expected Furthermore, the evaluation of follow-up investigation should clarify whether patients with cardiac amyloidosis suffer a faster progression of their AS than those without amyloidosis.
A comparison of the imaging modalities (CMR and SZG) will provide clues for further delineation of the indication. of these in order to develop targeted diagnostic algorithms that are as efficient as possible.
- Conditions
- Amyloidosis, Aortic Valve Stenosis
- Being tested
- CMR, scintigraphy
- Keywords
- Amyloidosis, Aortic Valve Stenosis, MRI, myocardial scintigraphy, screening algorithm, early detection
- Medical subject headings
- Amyloidosis, Aortic Valve Stenosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CMROther
clinical indication
scintigraphyOther
clinical indication
| Study group | Role | What they receive |
|---|---|---|
| retrospective | For the retrospective part of the study, the existing echocardiographic database will be used to retrieve data. The database query includes the last 2 years. Receives: Other: CMR; Other: scintigraphy | |
| prospective | For the prospective part of the study, patients will be included who have the clinical indication for cmr and scintigraphy due to suspected cardiac amyloidosis and fulfill the inclusion criteria. Receives: Other: CMR; Other: scintigraphy |
What is being measured
The primary outcome is the main question the study is designed to answer.
prevalence of cardiac amyloidosis in mild-to-moderate AS
estimating the prevalence of cardiac amyloidosis
Measured: up to two years
Secondary outcomes (1)
frequency of more rapid progression of AS in patients with cardiac amyloidosis than those without
frequency of more rapid progression of AS in patients with cardiac amyloidosis than those
Measured: up to two years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2021
- Study start1 Aug 2021
- Primary completionSep 2023 (estimated)
- Study completionSep 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AmyloidosisStudies of the same condition, open and under way.
- More trials run by Heinrich-Heine University, DuesseldorfThe 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
- Other
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Heinrich-Heine University, Duesseldorf
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ralf Westenfeld, MD, Principal investigator, Division. of Cardiology, Pulmonary Disease and Vascular Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05010980
- Sponsor's protocol ID
- 21-002
- Status last verified
- Oct 2022
- First submitted
- 5 Aug 2021
- Last updated
- 31 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Detection of Cardiac Amyloidosis Among Patients With Aortic Valve Stenosis.
- ClinicalTrials.gov ID
- NCT05010980
- Acronym / sponsor ID
- 21-002
- Conditions
- Amyloidosis, Aortic Valve Stenosis
- Keywords
- Amyloidosis, Aortic Valve Stenosis, MRI, myocardial scintigraphy, screening algorithm, early detection
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- Heinrich-Heine University, DuesseldorfUniversity, hospital or other
- Study start
- 1 Aug 2021 (actual)
- Primary completion
- Sep 2023 (estimated)
- Study completion
- Sep 2023 (estimated)
- First posted
- 18 Aug 2021 (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.
Due to a lack of therapeutic options, the diagnosis of cardiac (wt)-ATTR amyloidosis was for a long time overshadowed by other diseases and therefore was or still is often diagnosed with considerable delay.
The aim of the study is to estimate the prevalence of cardiac amyloidosis among patients with mild-to-moderate aortic valve stenosis (AS).
Besides that a screening algorithm based on echocardiographic parameters will be developed, to facilitate the early detection of cardiac amyloidosis.
Detailed description
Due to a lack of therapeutic options, the diagnosis of cardiac (wt)-ATTR amyloidosis was for a long time overshadowed by other diseases and therefore was or still is often diagnosed with considerable delay. On the one hand, it was assumed that the number of cases was significantly lower than the latest studies showed, and on the other hand, until the introduction of new therapeutic agents, there was no approved therapeutic option available, so that the corresponding diagnosis did not result in any therapeutic consequences.
This has changed fundamentally in recent years. For example, analyses of patients who underwent interventional aortic valve replacement (TAVI) as a result of high-grade AS demonstrated cardiac amyloidosis in up to 16% of these patients. Patients with (paradoxical) low flow low gradient (lflg) AS, which is echocardiographically characterized by a low stroke volume index (SVI), are particularly frequently affected. In light of these data, recent publications recommend the use of a low SVI, in conjunction with ECG criteria (low Sokolow-Lyon index) relative to echocardiographically determined left ventricular myocardial mass (SLI/ LVM) as a screening tool for the presence of amyloidosis in the patient population with high-grade aortic valve stenosis.
In patients with mild-to-moderate AS, the prevalence of amyloidosis and the validity of these methods has not yet been clarified. However, identification of these would be, of particular interest, especially in view of the new therapy options, since with the modern therapy methods can only improve prognosis if the diagnosis is made early.
When cardiac amyloidosis is suspected, three procedures are currently used in clinical practice
- myocardial biopsy (BX)
- cardiac MRI (CMR)
- scintigraphy with 99mTc phosphates as tracer (scintigraphy)
Myocardial biopsy is not suitable as a broad screening method due to cost, effort, and limited feasibility at designated centers. It's rather a goldstandard for confirming nonconclusive findings or for further differential diagnosis or prognostic assessment.
Scintigraphy and CMR are the established and regularly used methods for the detection of cardiac amyloidosis.
Scintigraphy is a cost-effective examination that can be performed on an outpatient basis with low radiation exposure and high sensitivity and specificity for the detection of cardiac (ATTR) amyloidosis, especially in (still) asymptomatic patients. Scintigraphy is already recommended for the screening of ATTR amyloidosis. Besides scintigraphy, the CMR also offers good sensitivity (80%) and specificity (94%) for the diagnosis of cardiac amyloidosis, CMR also offers the advantage of a comprehensive cardiac differential diagnosis with possible exclusion of amyloidosis. It can also be performed on an outpatient basis, does not require a radiation-based procedure and can diagnose cardiac amyloidosis with high reproducibility, both with and without contrast medium. Which of the latter two examinations is more suitable for amyloidosis screening has not been conclusively determined. Although CMR and scintigraphy are regulary used for amyloidosis screening, it is not yet known, which of the two examinations is more suitable.
The aim of the study is to estimate the prevalence of cardiac amyloidosis in mild-to-moderate AS.
Furthermore, a screening algorithm based on echocardiographic parameters should be developed, to facilitate the early detection of cardiac amyloidosis: This would allow earlier initiation of therapy and thus better therapeutic success in patients with cardiac amyloidosis. Accordingly, a better quality of life as well as a prolonged survival of these severely affected patients could be expected Furthermore, the evaluation of follow-up investigation should clarify whether patients with cardiac amyloidosis suffer a faster progression of their AS than those without amyloidosis.
A comparison of the imaging modalities (CMR and SZG) will provide clues for further delineation of the indication. of these in order to develop targeted diagnostic algorithms that are as efficient as possible.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| retrospective | – | Other: CMR, Other: scintigraphyFor the retrospective part of the study, the existing echocardiographic database will be used to retrieve data. The database query includes the last 2 years. |
| prospective | – | Other: CMR, Other: scintigraphyFor the prospective part of the study, patients will be included who have the clinical indication for cmr and scintigraphy due to suspected cardiac amyloidosis and fulfill the inclusion criteria. |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
- Study population
- patients undergoing a routine echocardiographic assessment which results in the clinical indication for CMR and scintigraphy among patients with aortic valve stenosis
Key inclusion criteria (6 listed)
- Age > 65 years
- Patients who fulfill at least 3 of the following 4 criteria based on cardiac ultrasound examination, which results in the clinical indication for CMR and scintigraphy
- Evidence an aortic valve stenosis, defined as opening area according to velocity time integral (VTI) < 2cm2
- Hypertrophy of the interventricular septum (IVS) > 11mm
- Echocardiographically assesed reduced stroke volume index (SVI) (< 35 ml/m2)
Key exclusion criteria (3 listed)
- Patients who are incapable of giving consent,
- Age < 65 years
- patients who have not given their written consent
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 |
|---|---|---|
| CMRclinical indication | Other | prospective, retrospective |
| scintigraphyclinical indication | Other | prospective, retrospective |
Primary outcome
prevalence of cardiac amyloidosis in mild-to-moderate AS
Time frame: up to two years
estimating the prevalence of cardiac amyloidosis
1 secondary outcome
frequency of more rapid progression of AS in patients with cardiac amyloidosis than those without
Time frame: up to two years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2022.
- Individual participant dataSharing planned: Undecided
Related trials for Amyloidosis
Not yet recruiting
Acupressure as Long-term Intervention to Slow the Progression of Early/Mild Alzheimer's Disease
Alzheimer's Disease
Active, not recruitingPhase 2
A Study to Evaluate the Safety and Biomarker Effects of RO7269162 in Participants at Risk for or at the Prodromal Stage of Alzheimer's Disease (AD)
Alzheimer's Disease
Active, not recruitingObservational study
A Retrospective Observational Study of Epidemiology and Outcomes in Transthyretin Amyloid Cardiomyopathy in Germany
ATTR-CM (Transthyretin Amyloid Cardiomyopathy)
Active, not recruitingPhase 3
EPIC-ATTR: A Study to Evaluate the Effect of Eplontersen on the Transthyretin Reduction and Long-term Safety in Chinese Subjects With Transthyretin Amyloid Cardiomyopathy
Transthyretin Amyloid Cardiomyopathy
RecruitingObservational study
PET Imaging in the Baltimore Longitudinal Study of Aging (BLSA)
Aging
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.
Ralf Westenfeld, MD principal investigator
Division. of Cardiology, Pulmonary Disease and Vascular Medicine
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 Amyloidosis and Aortic Valve Stenosis, run by Heinrich-Heine University, Duesseldorf at 1 site in Germany.
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 6 inclusion and 3 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 31 Oct 2022. 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 Germany. 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 Ralf Westenfeld, MD (0049211 8118800, ctu@med.uni-duesseldorf.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
prevalence of cardiac amyloidosis in mild-to-moderate AS (time frame: up to two years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 31 Oct 2022.