Patient-Reported Outcome Measures in Wild-Type and Variant Cardiac Transthyretin Amyloidosis (ITALY)

• ClinicalTrials.gov Identifier: NCT04563286
• Recruitment Status: Unknown
• First Posted: September 24, 2020
• Last Update Posted: September 24, 2020
• Sponsor: University of Messina
• Collaborators: Fondazione Toscana Gabriele Monasterio; University of Pavia; Università degli Studi di Ferrara; Careggi Hospital
• Information provided by (Responsible Party): Gianluca Di Bella, University of Messina

Study Description

Brief Summary:

Specific, standardized, comprehensive, universally accepted Patient-Reported Outcome Measures (PROMs) are currently lacking for variant and wild-type cardiac amyloid transthyretin amyloidosis (v-ATTR/wt-ATTR). Our goal is then to create two scores able to provide a cumulative assessment of cardiac involvement, peripheral neuropathy (in v-ATTR), and comorbidities, and their impact on the quality of life.

In the setting of a nationwide collaboration involving 5 main Italian referral centers for this condition (in Ferrara, Florence, Pavia, Pisa and Messina), a panel will be created, including experts of ATTR cardiomyopathy, neurologists, geriatricians, health management specialists, as well as patients with either variant or wild-type ATTR cardiomyopathy (n=50).

The most clinically relevant domains for patients (such as physical limitations, symptoms, self-efficacy and knowledge, social interference, quality of life, age-related issues, social and family environment, frailty, comorbidities) will be identified. Two sets of 30 items (one for variant and another for wild-type ATTR cardiomyopathy) will be created in collaboration with patients. Questions will be formatted for gender neutrality, clarity, interpretability, and possible foreign language translations. PROMs scores will be validated through administration to around 250 consecutive outpatients. Score performance will be evaluated in terms of internal consistency, response to clinical changes, comparison with conventional clinical measures. The time needed for completion, the clarity of questions and the need for assistance from a family caregiver will be evaluated.

This project will hopefully lead to the identification of disease-specific metrics that may serve as a clinically meaningful outcome in cardiovascular research, patient management, and quality assessment.

Condition or disease	Intervention/treatment
Transthyretin Amyloidosis	Other: questionnaire on life quality

Study Design

• Study Type: Observational
• Estimated Enrollment: 250 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Patient-Reported Outcome Measures in Wild-Type and Variant Cardiac Transthyretin Amyloidosis: The Impact of Transthyretin Amyloidosis on Life qualitY (ITALY) Study
• Actual Study Start Date: February 22, 2020
• Estimated Primary Completion Date: April 22, 2022
• Estimated Study Completion Date: June 22, 2022

Groups and Cohorts

Intervention Details:

• Other: questionnaire on life quality
  Two sets of 30 PROMs questions will be created. The v-ATTR and wt-ATTR questionnaires will be critically evaluated by the whole panel, taking into account observations and feedback from patients. The 2 scores will be administered to consecutive patients evaluated at dedicated ambulatory clinics of the 4 Institutions. To confirm score reliability and responsiveness, 2 distinct patient cohorts will be recruited. The reliability cohort will be assembled to demonstrate the instrument's test-retest reliability. A second cohort of patients (responsiveness cohort) will be assembled to demonstrate the instrument's responsiveness to changes in clinical status. Patients experiencing a heart failure hospitalization within 6 months will enter the responsiveness cohort at the time of hospital admission.

Outcome Measures

Primary Outcome Measures :

1. reliability [ Time Frame: baseline to 6 months ]
   internal consistency

Secondary Outcome Measures :

1. responsiveness [ Time Frame: baseline to HF hospitalization (<6 months) ]
   changes in scores in response to clinical changes
2. validity of each domain [ Time Frame: baseline to 6 months ]
   comparison of scores with other measures that quantify similar concepts, namely other score points, NYHA class, 6MWD, or objective measures of cardiac dysfunction, i.e. circulating levels of NT-proBNP and hs-TnT)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Patients with cardiac ATTR amyloidosis, either biopsy proven or diagnosed according to the algorithm for nonbiopsy diagnosis of ATTR cardiomyopathy (Gillmore et al., 2016), will be evaluated.

PROMs for v-ATTR and wt-ATTR will be created in close collaboration with 50 patients suffering from ATTR cardiomyopathy (see below), and will be validated on a cohort of 250 patients (i.e., 50 patients from each participating center; see below).

Criteria

Inclusion Criteria:

• Diagnosis of cardiomyopathy due to ATTR amyloidosis, diagnosed by endomyocardial biopsy or on the basis of the algorithm for the non-invasive diagnosis of cardiac ATTR amyloidosis (Gillmore et al., 2016).
• Clinical stability, defined as the lack of unscheduled hospitalizations and/or significant changes in cardiac therapies from at least 1 month.

Exclusion Criteria:

• Lack of informed consent.
• Inability of understanding a written text in Italian.
• Absence of the conditions of clinical stability, as defined above.

Contacts and Locations

Locations

Italy

Università di Ferrara; Recruiting

Ferrara, Italy

Contact: Claudio Rapezzi +390532293111 claudio.rapezzi@unife.it

Careggi Hospital; Recruiting

Firenze, Italy

Contact: Francesco Cappelli, MD +39 055 794 9946 cappellifrancesco@inwind.it

Contact: MD

Sub-Investigator: Francesco Cappelli, MD

Principal Investigator: Federico Perfetto

Università di Messina; Recruiting

Messina, Italy

Contact: Gianluca Di Bella +393205506147 gianluca.dibella@unime.it

Università di Pavia; Recruiting

Pavia, Italy

Contact: Giovanni Palladini +390382989898 giovanni.palladini@unipv.it

Fondazione Toscana Gabriele Monasterio (FTGM); Recruiting

Pisa, Italy, 56124

Contact: Michele Emdin +393454744053 emdin@ftgm.it

Sub-Investigator: Claudio Passino, MD

Sponsors and Collaborators

University of Messina

Fondazione Toscana Gabriele Monasterio

University of Pavia

Università degli Studi di Ferrara

Careggi Hospital

More Information

• Responsible Party: Gianluca Di Bella, Professor, University of Messina
• ClinicalTrials.gov Identifier: NCT04563286
• Other Study ID Numbers: IT08012020
• First Posted: September 24, 2020
• Last Update Posted: September 24, 2020
• Last Verified: September 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Gianluca Di Bella, University of Messina:

amyloidosis; transthyretin; quality of life; score; cardiomyopathy

Additional relevant MeSH terms:

Amyloid Neuropathies, Familial; Amyloidosis; Proteostasis Deficiencies; Metabolic Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Amyloid Neuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Amyloidosis, Familial; Metabolism, Inborn Errors