Comprehensive Program for Hereditary Transthyretin Amyloidosis

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.

Study Overview

• Status: Recruiting
• Conditions: Amyloidosis, Familial; Amyloidosis in Transthyretin (TTR)
• Intervention / Treatment: Other: clinical assessments and complementary examinations

• Study Type: Observational
• Enrollment (Estimated): 20

Contacts and Locations

• Study Contact: Name: Gisela Zanga, MD; Phone Number: +5491156074899; Email: gzanga84@hotmail.com

Study Locations

• Argentina
  • Buenos Aires
    • Cañuelas, Buenos Aires, Argentina, 1814
      • Recruiting
      • Hospital Cuenca Alta de Cañuelas
      • Contact: Debora Nadur, MD; Phone Number: +5491139180350; Email: debonadur@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Participants over 18 years of age diagnosed with hereditary transthyretin amyloidosis with a pathogenic variant of the TTR gene confirmed by genetic testing, whether symptomatic and/or with suspected disease progression, as well as asymptomatic carriers of these variants, will be included.

Description

Inclusion Criteria:

-Participants with a pathogenic variant of the TTR gene (Hereditary Amyloidosis)

Exclusion Criteria:

• wild-type TTR amyloidosis

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Participants over 18 years of age diagnosed with hereditary transthyretin amyloidosis; Participants with a pathogenic variant of the TTR gene confirmed by genetic testing, whether symptomatic and/or with suspected disease progression, as well as asymptomatic carriers of these variants, will be included. Individuals with wild-type TTR amyloidosis will be excluded .

Other: clinical 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phenotypic classification	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.; 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.	3 YEARS

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in New York Heart Association (NYHA) functional class	Functional class assessed using the NYHA scale (range I-IV, higher class indicates worse cardiac function).	3 years
Change from baseline in 6-Minute Walk Test (6MWT) distance	Distance walked in meters will be measured according to ATS guidelines. Lower values indicate reduced functional capacity	3 years
Change from baseline in N-terminal pro-brain natriuretic peptide (Pro-BNP)	Serum concentration measured in pg/mL. Higher values indicate worse cardiac function.	3 years
Change from baseline in Troponin T	Serum concentration measured in ng/L. Higher values indicate myocardial injury	3 years
Change from baseline in Microalbuminuria	Urinary albumin excretion measured in mg/24h. Higher values indicate worse renal involvement.	3 years
Change from baseline in Left Ventricular Ejection Fraction	Ejection fraction (%) measured by echocardiography. Lower values indicate worse cardiac function	3 years
Change from baseline in Left Ventricular Wall Thickness	Wall thickness measured in millimeters by echocardiography. Higher values indicate worse disease progression.	3 years
Change from baseline in diastolic dysfunction grade	Diastolic dysfunction assessed by echocardiography following ASE guidelines. Higher grade indicates worse dysfunction.	3 years
Incidence of atrial fibrillation, atrioventricular block, or PR interval prolongation	Presence of atrial fibrillation, new AV block, or PR interval prolongation assessed by ECG. Categorical outcome (Yes/No).	3 years
Change from baseline in Coutinho/PND (Polyneuropathy Disability) score	Score range 0-IV; higher score indicates greater disability	3 years
Change from baseline in Neuropathy Impairment Score (NIS)	Total score range 0-244; higher values indicate worse neuropathy.	3 years
Change from baseline in COMPASS-31 total score	Questionnaire score range 0-100; higher values indicate worse autonomic symptoms.	3 years
Change from baseline in Norfolk QoL-DN score	Total score range -4 to 136; higher values indicate worse quality of life related to neuropathy.	3 years
Change from baseline in RODS (Rasch-built Overall Disability Scale)	Score range 0-48; lower values indicate greater disability	3 years
Change from baseline in Body Mass Index (BMI)	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.	3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minimum criteria	To explore minimum criteria for disease onset in patients initially considered asymptomatic: A quantified symptom or sign definitely related to the onset of the disease.Sensorimotor neuropathyAutonomic neuropathyHeart involvementKidney or eye involvement either; Any likely related symptoms plus 1 abnormal test result. either; Absence of symptoms and 2 abnormal test results	3 years

Collaborators and Investigators

• Sponsor: Hospital de Alta Complejidad en Red

Publications and helpful links

General Publications

• Pinto MV, Barreira AA, Bulle AS, Freitas MRG, Franca MC Jr, Gondim FAA, Marrone CD, Marques W Jr, Nascimento OJM, Rotta FT, Pupe C, Waddington-Cruz M. Brazilian consensus for diagnosis, management and treatment of transthyretin familial amyloid polyneuropathy. Arq Neuropsiquiatr. 2018 Sep;76(9):609-621. doi: 10.1590/0004-282X20180094.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2025
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: September 5, 2025
• First Submitted That Met QC Criteria: October 1, 2025
• First Posted (Actual): October 8, 2025

Study Record Updates

• Last Update Posted (Actual): March 24, 2026
• Last Update Submitted That Met QC Criteria: March 20, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: amyloidosis; transthyretin; comprensive care
• Additional Relevant MeSH Terms: Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Proteostasis Deficiencies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Amyloidosis; Amyloidosis, Familial
• Other Study ID Numbers: ESCAN

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No