Amyloidosis, Familial, Amyloidosis in Transthyretin (TTR)
Conditions
Keywords
transthyretin, amyloidosis, comprensive care
Brief summary
The Comprehensive Program for Hereditary Transthyretin Amyloidosis describes a prospective observational study focused on understanding hereditary transthyretin amyloidosis (ATTR), a progressive and potentially fatal condition marked by amyloid fibril deposits impacting multiple organs. The trial aims to characterize patient phenotypes, investigate factors affecting disease progression, and identify minimum criteria for disease onset. Conducted at Néstor Kirchner Hospital, the trial enrolls participants over 18 years old with confirmed pathogenic TTR variants. It includes thorough evaluations such as genetic testing sponsored by pharmaceutical companies, clinical assessments, and diverse diagnostic tests.
Interventions
OTHERclinical assessments and complementary examinations
Evaluation Plan Comprehensive Examination: Complete medical history and physical examination of all body systems, including height and weight measurements. Clinical Parameters: Pulse/heart rate, respiratory rate, and SpO2 will be monitored. The NYHA classification will be used to assess heart failure if applicable. Neurological Examination: Includes motor strength testing, sensory testing (pinprick, light touch, temperature, proprioception), deep tendon reflexes, and gait assessment. Electrocardiogram (ECG): A 12-lead ECG will be performed with the subject at rest for at least 5 minutes in a supine position. 24-hour Holter Monitoring: Conducted in cases of suspected arrhythmias or echocardiographic findings indicating arrhythmias. Color Dosments and complementary examinations
Sponsors
Hospital de Alta Complejidad en Red
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
-Participants with a pathogenic variant of the TTR gene (Hereditary Amyloidosis)
Exclusion criteria
* wild-type TTR amyloidosis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phenotypic classification | 3 YEARS | 1. Predominantly Cardiac Phenotype: Patients will present with abnormal electrocardiograms (ECG) due to rhythm disturbances, heart failure, or dyspnea. They will exhibit no more than mild neurological or gastrointestinal (GI) symptoms. Conditions such as erectile dysfunction, constipation, and carpal tunnel syndrome will be excluded from this phenotype. 2. Predominantly Neurological Phenotype: Patients will exhibit neurological or GI symptoms of any severity. They will not have abnormal ECGs due to rhythm disturbances, heart failure, or dyspnea. Neurological and GI symptoms will need to be continuous and definitively linked to amyloidosis. 3\]) Mixed Phenotype: Patients will present with abnormal ECGs due to rhythm disturbances, heart failure, or dyspnea. They will also have neurological or GI symptoms of any severity. These patients will not meet the criteria for a predominantly cardiac or neurological phenotype. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in New York Heart Association (NYHA) functional class | 3 years | Functional class assessed using the NYHA scale (range I-IV, higher class indicates worse cardiac function). |
| Change from baseline in 6-Minute Walk Test (6MWT) distance | 3 years | Distance walked in meters will be measured according to ATS guidelines. Lower values indicate reduced functional capacity |
| Change from baseline in N-terminal pro-brain natriuretic peptide (Pro-BNP) | 3 years | Serum concentration measured in pg/mL. Higher values indicate worse cardiac function. |
| Change from baseline in Troponin T | 3 years | Serum concentration measured in ng/L. Higher values indicate myocardial injury |
| Change from baseline in Microalbuminuria | 3 years | Urinary albumin excretion measured in mg/24h. Higher values indicate worse renal involvement. |
| Change from baseline in Left Ventricular Ejection Fraction | 3 years | Ejection fraction (%) measured by echocardiography. Lower values indicate worse cardiac function |
| Change from baseline in Left Ventricular Wall Thickness | 3 years | Wall thickness measured in millimeters by echocardiography. Higher values indicate worse disease progression. |
| Change from baseline in diastolic dysfunction grade | 3 years | Diastolic dysfunction assessed by echocardiography following ASE guidelines. Higher grade indicates worse dysfunction. |
| Incidence of atrial fibrillation, atrioventricular block, or PR interval prolongation | 3 years | Presence of atrial fibrillation, new AV block, or PR interval prolongation assessed by ECG. Categorical outcome (Yes/No). |
| Change from baseline in Coutinho/PND (Polyneuropathy Disability) score | 3 years | Score range 0-IV; higher score indicates greater disability |
| Change from baseline in Neuropathy Impairment Score (NIS) | 3 years | Total score range 0-244; higher values indicate worse neuropathy. |
| Change from baseline in COMPASS-31 total score | 3 years | Questionnaire score range 0-100; higher values indicate worse autonomic symptoms. |
| Change from baseline in Norfolk QoL-DN score | 3 years | Total score range -4 to 136; higher values indicate worse quality of life related to neuropathy. |
| Change from baseline in RODS (Rasch-built Overall Disability Scale) | 3 years | Score range 0-48; lower values indicate greater disability |
| Change from baseline in Body Mass Index (BMI) | 3 years | BMI calculated as weight (kg)/height (m²). Both weight and height will be measured and aggregated to report BMI. Higher or lower values may reflect disease progression. |
Countries
Argentina
Contacts
CONTACTGisela Zanga, MD
Outcome results
None listed