Morpho-functional Cardiac Modifications in Treated Mutated Transthyretin Cardiac Amyloidosis

NCT04387344 | Unknown

• 1 other identifier: UNIME_CARD_2
• Study Type: observational
• Target: 25
• Locations: 1 country
• Sites: 2

Brief 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. 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.

Conditions

Cardiac Amyloidosis

Outcome Measures

Primary Outcomes (2)

• Change of Atrial and Ventricular Walls Dimensions

  Measurements (mm) of Interatrial Septum, Ventricular Walls, Coumadin Ridge, Mitro-aortic Lamina, Valves

  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)

  Change from Baseline Atrial and Ventricular Strain to 18 months

Secondary Outcomes (1)

• Change of Myocardial Work index of Left Ventricle

  Change from Baseline Myocardial work to 18 months

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

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.

You may qualify if:

• 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,

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Messina: lead
• Campisi Mariapaola: collaborator

Study Sites (2)

Careggi Hospital

Florence, Italy

Location

Fondazione Policlinico Universitario A. Gemelli IRCCS.

Roma, Italy

Location

Related Publications (6)

• 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.

  PMID: 25190073 RESULT

• Di 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.

  PMID: 26253999 RESULT

• Di 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.

  PMID: 21427499 RESULT

• Emdin 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.

  PMID: 31111153 RESULT

• Benson 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.

  PMID: 29972757 RESULT

• Adams 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.

  PMID: 29972753 RESULT

MeSH Terms

Conditions

Amyloid Neuropathies, Familial

Condition Hierarchy (Ancestors)

Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Amyloid Neuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Amyloidosis, Familial; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Amyloidosis; Proteostasis Deficiencies

Study Officials

• Gianluca Di Bella, MD

  University of Messina, Italy

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Francesco Cappelli, MD

CONTACT

+39 055 794 9946; cappellifrancesco@inwind.it

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor Cardiovascular Diseases

Study Record Dates

• First Submitted: May 3, 2020
• First Posted: May 13, 2020
• Study Start: May 20, 2020
• Primary Completion: June 30, 2020
• Study Completion: December 30, 2020
• Last Updated: May 13, 2020

Record last verified: 2020-05

Locations

IT (2)