Cardiac AmyloidosisNCT04387344
Morpho-functional Cardiac Modifications in Treated Mutated Transthyretin Cardiac Amyloidosis
An observational study of Cardiac Amyloidosis, run by University of Messina at 2 sites in Italy.
Trial summary
Cardiac Amyloidosis (CA) is characterized by a long subclinical phase characterized by deposition of amyloid fibrils in atria, valves and walls of ventricles. Longitudinal dysfunction of the left ventricle (LV) with preserved ejection fraction (EF) is the early phase of CA. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Cardiac Amyloidosis
- How many people
- 25 participants
- Where
- 2 sitesItaly
- Study dates
- 20 May 2020to 30 Dec 2020
- 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 90 years
- All sexes
- Adult, Older adult
Study population: Consecutive patients with a diagnosis amyloidosis treated with RNA interferences. A diagnosis of cardiac amyloidosis requires left ventricular wall thickness of ≥12 and a positive perugini score (grade 2-3) on technetium-99m(99mTc)-diphosphonate (DPD) or 99mTc-hydroxyl-methylene-diphosphonate (HMDP) bone scintigraphy.
Who may be able to join
- presence of data obtained from historical records of patients who retrospectively met the prescriptive (neurological) criteria and received the prescription of the drugs in question (RNA interferences) having
- Cardiological evaluation (examination ECG, echocardiography) at the time of prescription
- Cardiological evaluation (examination ECG, echocardiography) evaluated six months after therapy,
- Cardiological evaluation (examination ECG, echocardiography) evaluated 12-18 months after therapy,
Who cannot join
- it wasn't possible to putatively confirm the reasonable shipment of the innovative therapy prescribed
- it wasn't possible to putatively confirm the reasonable shipment of conventional therapy prescribed (background therapy)
Trial locations and contacts
2 sites in 1 country.
Italy2 sites
Careggi Hospital
Florence
Francesco Cappelli, MD, +39 055 794 9946, cappellifrancesco@inwind.it
MD
Fondazione Policlinico Universitario A. Gemelli IRCCS.
Roma
Marco Luigetti, marco.luigetti@policlinicogemelli.it
Marco Luigetti
About this study
Official title: Cardiac Modifications in Transthyretin Cardiac Amyloidosis
Cardiac Amyloidosis (CA) is characterized by a long subclinical phase characterized by deposition of amyloid fibrils in atria, valves and walls of ventricles. Longitudinal dysfunction of the left ventricle (LV) with preserved ejection fraction (EF) is the early phase of CA.
Longitudinal dysfunction mainly involves the LV basal and middle segments with less involvement of the distal segments (apical sparing).
Read more
Strain echocardiography (STE) measures myocardial deformation. The technique has been shown to be sensitive for early detection of impaired systolic function and for the study of CA. Additionally, cardiac efficiency (myocardial work) can be derived from myocardial strain data analysis.
In the year 2018, "RNA interferences" (patisiran and inotersen) were included in the list of compassionate therapeutic use programs for exclusive use for the treatment of adult patients with hereditary amyloidosis neuropathy. The aim of our study is to evaluate the morpho-functional modifications with RNA interferences.
Read the detailed description
Transthoracic echocardiographic images are recorded in the available ultrasound units (Vivid 7 and Vivid 9, GE Ultrasound, Horten, Norways and MyLab - Esaote, Genoa, Italy). The diameters and the wall thicknesses are measured according to the insurance of the American Society of Echocardiography. The images obtained with apical view and in format 4 bedrooms with frame rates (70-80 frames / s) - stored for three cardiac cycles in cine-loop format - will be used for evaluate off-line to evaluate left ventricle deformation in the longitudinal and radial direction, basalelateral, and top segments (post processing) through software already in use and available (Suitestenza, Esaote, Florence, Italy and GE Ultrasound, Horten, Norway).
- Conditions
- Cardiac Amyloidosis
- Medical subject headings
- Amyloid Neuropathies, Familial
What is being measured
The primary outcome is the main question the study is designed to answer.
Change of Atrial and Ventricular Walls Dimensions
Measurements (mm) of Interatrial Septum, Ventricular Walls, Coumadin Ridge, Mitro-aortic Lamina, Valves
Measured: Change from Baseline Wall Thickness to 18 months
Change of Atrial and Ventricular Strain
Mean paired change in myocardial strain (percent) by echocardiographic strain-rate imaging (unitless)
Measured: Change from Baseline Atrial and Ventricular Strain to 18 months
Secondary outcomes (1)
Change of Myocardial Work index of Left Ventricle
Evaluation of the Global work index (GWI): total work within the area of the LV pressure-strain loops calculated from mitral valve closure to mitral valve opening.
Measured: Change from Baseline Myocardial work to 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2020
- Study start20 May 2020 (estimated)
- Primary completion30 Jun 2020 (estimated)
- Study completion30 Dec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Cardiac AmyloidosisStudies 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
- Case only
- Time perspective
- Retrospective
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Messina
- Sponsor type
- University, hospital or other
- Collaborators
- Campisi Mariapaola
- Responsible party
- Principal investigator, Gianluca Di Bella, University of Messina
- Investigators
- Gianluca Di Bella, MD, Principal investigator, University of Messina, Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04387344
- Sponsor's protocol ID
- UNIME_CARD_2
- Status last verified
- May 2020
- First submitted
- 3 May 2020
- Last updated
- 13 May 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Di Bella G, Pizzino F, Minutoli F, Zito C, Donato R, Dattilo G, Oreto G, Baldari S, Vita G, Khandheria BK, Carerj S. The mosaic of the cardiac amyloidosis diagnosis: role of imaging in subtypes and stages of the disease. Eur Heart J Cardiovasc Imaging. 2014 Dec;15(12):1307-15. doi: 10.1093/ehjci/jeu158. Epub 2014 Sep 4.
PubMed 25190073Di Bella G, Minutoli F, Piaggi P, Casale M, Mazzeo A, Zito C, Oreto G, Baldari S, Vita G, Pingitore A, Khandheria BK, Carerj S. Usefulness of Combining Electrocardiographic and Echocardiographic Findings and Brain Natriuretic Peptide in Early Detection of Cardiac Amyloidosis in Subjects With Transthyretin Gene Mutation. Am J Cardiol. 2015 Oct 1;116(7):1122-7. doi: 10.1016/j.amjcard.2015.07.008. Epub 2015 Jul 16.
PubMed 26253999Di Bella G, Minutoli F, Pingitore A, Zito C, Mazzeo A, Aquaro GD, Di Leo R, Recupero A, Stancanelli C, Baldari S, Vita G, Carerj S. Endocardial and epicardial deformations in cardiac amyloidosis and hypertrophic cardiomyopathy. Circ J. 2011;75(5):1200-8. doi: 10.1253/circj.cj-10-0844. Epub 2011 Mar 17.
PubMed 21427499Emdin M, Aimo A, Rapezzi C, Fontana M, Perfetto F, Seferovic PM, Barison A, Castiglione V, Vergaro G, Giannoni A, Passino C, Merlini G. Treatment of cardiac transthyretin amyloidosis: an update. Eur Heart J. 2019 Dec 1;40(45):3699-3706. doi: 10.1093/eurheartj/ehz298.
PubMed 31111153Benson MD, Waddington-Cruz M, Berk JL, Polydefkis M, Dyck PJ, Wang AK, Plante-Bordeneuve V, Barroso FA, Merlini G, Obici L, Scheinberg M, Brannagan TH 3rd, Litchy WJ, Whelan C, Drachman BM, Adams D, Heitner SB, Conceicao I, Schmidt HH, Vita G, Campistol JM, Gamez J, Gorevic PD, Gane E, Shah AM, Solomon SD, Monia BP, Hughes SG, Kwoh TJ, McEvoy BW, Jung SW, Baker BF, Ackermann EJ, Gertz MA, Coelho T. Inotersen Treatment for Patients with Hereditary Transthyretin Amyloidosis. N Engl J Med. 2018 Jul 5;379(1):22-31. doi: 10.1056/NEJMoa1716793.
PubMed 29972757Adams D, Gonzalez-Duarte A, O'Riordan WD, Yang CC, Ueda M, Kristen AV, Tournev I, Schmidt HH, Coelho T, Berk JL, Lin KP, Vita G, Attarian S, Plante-Bordeneuve V, Mezei MM, Campistol JM, Buades J, Brannagan TH 3rd, Kim BJ, Oh J, Parman Y, Sekijima Y, Hawkins PN, Solomon SD, Polydefkis M, Dyck PJ, Gandhi PJ, Goyal S, Chen J, Strahs AL, Nochur SV, Sweetser MT, Garg PP, Vaishnaw AK, Gollob JA, Suhr OB. Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis. N Engl J Med. 2018 Jul 5;379(1):11-21. doi: 10.1056/NEJMoa1716153.
PubMed 29972753
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cardiac Modifications in Transthyretin Cardiac Amyloidosis
- ClinicalTrials.gov ID
- NCT04387344
- Acronym / sponsor ID
- UNIME_CARD_2
- Conditions
- Cardiac Amyloidosis
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- University of MessinaUniversity, hospital or other
- Collaborators
- Campisi Mariapaola
- Study start
- 20 May 2020 (estimated)
- Primary completion
- 30 Jun 2020 (estimated)
- Study completion
- 30 Dec 2020 (estimated)
- First posted
- 13 May 2020 (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.
Cardiac Amyloidosis (CA) is characterized by a long subclinical phase characterized by deposition of amyloid fibrils in atria, valves and walls of ventricles. Longitudinal dysfunction of the left ventricle (LV) with preserved ejection fraction (EF) is the early phase of CA.
Longitudinal dysfunction mainly involves the LV basal and middle segments with less involvement of the distal segments (apical sparing).
Strain echocardiography (STE) measures myocardial deformation. The technique has been shown to be sensitive for early detection of impaired systolic function and for the study of CA. Additionally, cardiac efficiency (myocardial work) can be derived from myocardial strain data analysis.
In the year 2018, "RNA interferences" (patisiran and inotersen) were included in the list of compassionate therapeutic use programs for exclusive use for the treatment of adult patients with hereditary amyloidosis neuropathy. The aim of our study is to evaluate the morpho-functional modifications with RNA interferences.
Detailed description
Transthoracic echocardiographic images are recorded in the available ultrasound units (Vivid 7 and Vivid 9, GE Ultrasound, Horten, Norways and MyLab - Esaote, Genoa, Italy). The diameters and the wall thicknesses are measured according to the insurance of the American Society of Echocardiography. The images obtained with apical view and in format 4 bedrooms with frame rates (70-80 frames / s) - stored for three cardiac cycles in cine-loop format - will be used for evaluate off-line to evaluate left ventricle deformation in the longitudinal and radial direction, basalelateral, and top segments (post processing) through software already in use and available (Suitestenza, Esaote, Florence, Italy and GE Ultrasound, Horten, Norway).
Study design
- Observational model
- Case only
- Time perspective
- Retrospective
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- Consecutive patients with a diagnosis amyloidosis treated with RNA interferences. A diagnosis of cardiac amyloidosis requires left ventricular wall thickness of ≥12 and a positive perugini score (grade 2-3) on technetium-99m(99mTc)-diphosphonate (DPD) or 99mTc-hydroxyl-methylene-diphosphonate (HMDP) bone scintigraphy.
Key inclusion criteria (4 listed)
- presence of data obtained from historical records of patients who retrospectively met the prescriptive (neurological) criteria and received the prescription of the drugs in question (RNA interferences) having
- Cardiological evaluation (examination ECG, echocardiography) at the time of prescription
- Cardiological evaluation (examination ECG, echocardiography) evaluated six months after therapy,
- Cardiological evaluation (examination ECG, echocardiography) evaluated 12-18 months after therapy,
Key exclusion criteria (2 listed)
- it wasn't possible to putatively confirm the reasonable shipment of the innovative therapy prescribed
- it wasn't possible to putatively confirm the reasonable shipment of conventional therapy prescribed (background therapy)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Change of Atrial and Ventricular Walls Dimensions
Time frame: Change from Baseline Wall Thickness to 18 months
Measurements (mm) of Interatrial Septum, Ventricular Walls, Coumadin Ridge, Mitro-aortic Lamina, Valves
Change of Atrial and Ventricular Strain
Time frame: Change from Baseline Atrial and Ventricular Strain to 18 months
Mean paired change in myocardial strain (percent) by echocardiographic strain-rate imaging (unitless)
1 secondary outcome
Change of Myocardial Work index of Left Ventricle
Time frame: Change from Baseline Myocardial work to 18 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2020.
- Results publication: PubMed 25190073Di Bella G, Pizzino F, Minutoli F, Zito C, Donato R, Dattilo G, Oreto G, Baldari S, Vita G, Khandheria BK, Carerj S. The mosaic of the cardiac amyloidosis diagnosis: role of imaging in subtypes and stages of the disease. Eur Heart J Cardiovasc Imaging. 2014 Dec;15(12):1307-15. doi: 10.1093/ehjci/jeu158. Epub 2014 Sep 4.
- Results publication: PubMed 26253999Di Bella G, Minutoli F, Piaggi P, Casale M, Mazzeo A, Zito C, Oreto G, Baldari S, Vita G, Pingitore A, Khandheria BK, Carerj S. Usefulness of Combining Electrocardiographic and Echocardiographic Findings and Brain Natriuretic Peptide in Early Detection of Cardiac Amyloidosis in Subjects With Transthyretin Gene Mutation. Am J Cardiol. 2015 Oct 1;116(7):1122-7. doi: 10.1016/j.amjcard.2015.07.008. Epub 2015 Jul 16.
- Results publication: PubMed 21427499Di Bella G, Minutoli F, Pingitore A, Zito C, Mazzeo A, Aquaro GD, Di Leo R, Recupero A, Stancanelli C, Baldari S, Vita G, Carerj S. Endocardial and epicardial deformations in cardiac amyloidosis and hypertrophic cardiomyopathy. Circ J. 2011;75(5):1200-8. doi: 10.1253/circj.cj-10-0844. Epub 2011 Mar 17.
- Results publication: PubMed 31111153Emdin M, Aimo A, Rapezzi C, Fontana M, Perfetto F, Seferovic PM, Barison A, Castiglione V, Vergaro G, Giannoni A, Passino C, Merlini G. Treatment of cardiac transthyretin amyloidosis: an update. Eur Heart J. 2019 Dec 1;40(45):3699-3706. doi: 10.1093/eurheartj/ehz298.
- Results publication: PubMed 29972757Benson MD, Waddington-Cruz M, Berk JL, Polydefkis M, Dyck PJ, Wang AK, Plante-Bordeneuve V, Barroso FA, Merlini G, Obici L, Scheinberg M, Brannagan TH 3rd, Litchy WJ, Whelan C, Drachman BM, Adams D, Heitner SB, Conceicao I, Schmidt HH, Vita G, Campistol JM, Gamez J, Gorevic PD, Gane E, Shah AM, Solomon SD, Monia BP, Hughes SG, Kwoh TJ, McEvoy BW, Jung SW, Baker BF, Ackermann EJ, Gertz MA, Coelho T. Inotersen Treatment for Patients with Hereditary Transthyretin Amyloidosis. N Engl J Med. 2018 Jul 5;379(1):22-31. doi: 10.1056/NEJMoa1716793.
- Results publication: PubMed 29972753Adams D, Gonzalez-Duarte A, O'Riordan WD, Yang CC, Ueda M, Kristen AV, Tournev I, Schmidt HH, Coelho T, Berk JL, Lin KP, Vita G, Attarian S, Plante-Bordeneuve V, Mezei MM, Campistol JM, Buades J, Brannagan TH 3rd, Kim BJ, Oh J, Parman Y, Sekijima Y, Hawkins PN, Solomon SD, Polydefkis M, Dyck PJ, Gandhi PJ, Goyal S, Chen J, Strahs AL, Nochur SV, Sweetser MT, Garg PP, Vaishnaw AK, Gollob JA, Suhr OB. Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis. N Engl J Med. 2018 Jul 5;379(1):11-21. doi: 10.1056/NEJMoa1716153.
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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.
Gianluca Di Bella, MD principal investigator
University of Messina, Italy
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cardiac Amyloidosis, run by University of Messina at 2 sites in Italy.
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 2 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 13 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. 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 Francesco Cappelli, MD (+39 055 794 9946, cappellifrancesco@inwind.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of Atrial and Ventricular Walls Dimensions (time frame: Change from Baseline Wall Thickness to 18 months). 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 NCT04387344, which also lists 6 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 13 May 2020.