The Regional Scintigraphic DPD Uptake in Cardiac Transthyretin Amyloidosis.

Transthyretin Amyloidosis Clinical Trial

— AMYLOIDOZA  

Official title:

The Comparisons of Regional Scintigraphic DPD Uptake Between Patients With Hereditary and Wild Type Cardiac Transthyretin Amyloidosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05814380
• Other study ID #: ID#57165999
• Status: Recruiting
• Start date: May 4, 2020
• Est. completion date: March 1, 2024

Study information

• Verified date: April 2023
• Source: John Paul II Hospital, Krakow
• Contact: Katarzyna Holcman, MD, PhD
• Phone: +48 12 614 22 87
• Email: katarzyna.holcman[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Cardiac transthyretin (ATTR) amyloidosis is an infiltrative cardiomyopathy with an inexorably progressive clinical course and poor prognosis. The disease is caused by misfolding of the liver-derived precursor protein transthyretin as a result of an acquired wild-type variant (ATTRwt) or as a hereditary mutant variant (ATTRm). Application of single-photon emission computed tomography (SPECT) provides greater anatomic resolution, enabling the assessment of amyloid burden within individual left ventricle segments.This study aims to describe the pattern of regional myocardial distribution of 3,3-diphosphono-1,2-propanedicarboxylic acid (DPD) SPECT uptake among patients with ATTRwt and ATTRm. It will investigate the clinical, biochemical and echocardiographic, including left ventricle longitudinal strain profile in ATTRwt and ATTRm. Moreover, we will evaluate the presence and extent of DPD cardiac uptake among asymptomatic ATTRm variants carriers.This is a prospective multi-center observational study. The study, after obtaining prior written informed consent, will include consecutive patients who have Grade 1-3 cardiac DPD retention in scintigraphy. In addition, first-degree relatives of patients with ATTRm are going to be enrolled. Patients are going to undergo TTR gene sequencing to assess the presence of pathogenic variants associated with ATTRm. Both planar scintigraphy, SPECT and speckle-tracking echocardiography will be reviewed and interpreted using visual and quantitative approaches.

Description:

Cardiac transthyretin (ATTR) amyloidosis is an infiltrative cardiomyopathy with an inexorably progressive clinical course and poor prognosis. The disease is caused by misfolding of the liver-derived precursor protein transthyretin as a result of an acquired wild-type variant (ATTRwt) or as a hereditary mutant variant (ATTRm). Application of single-photon emission computed tomography (SPECT) provides greater anatomic resolution, enabling the assessment of amyloid burden within individual left ventricle segments.

This study aims to describe the pattern of regional myocardial distribution of 3,3-diphosphono-1,2-propanedicarboxylic acid (DPD) SPECT uptake among patients with ATTRwt and ATTRm. It will investigate the clinical, biochemical and echocardiographic, including left ventricle longitudinal strain profile in ATTRwt and ATTRm. Moreover, we will evaluate the presence and extent of DPD cardiac uptake among asymptomatic ATTRm variants carriers.

This is a prospective multi-center observational study. The study, after obtaining prior written informed consent, will include consecutive patients who have Grade 1-3 cardiac DPD retention in scintigraphy. In addition, first-degree relatives of patients with ATTRm are going to be enrolled. Patients are going to undergo TTR gene sequencing to assess the presence of pathogenic variants associated with ATTRm. Both planar scintigraphy, SPECT and speckle-tracking echocardiography will be reviewed and interpreted using visual and quantitative approaches.

The collected data will be analyzed statistically to verify research hypotheses. Approval from the local Bioethical Committee will be obtained before carrying out the study. All procedures performed are going to be in accordance with the ethical standards of the 1964 Helsinki declaration and its later amendments, or comparable ethical standards.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: March 1, 2024
• Est. primary completion date: March 1, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• over 18 years of age,

• providing written informed consent,

• grade 1-3 cardiac retention of 99mTc-DPD in scintigraphic study or a first-degree relative of a patient with ATTR

Exclusion Criteria:

-

Related Conditions & MeSH terms

• Amyloid Neuropathies, Familial
• Amyloidosis
• Transthyretin Amyloidosis

Intervention

Radiation:
• 99mTc-DPD scintigraphy
99mTc-DPD scintigraphy

Diagnostic Test:
• Collection of blood samples and echocardiography
Collection of blood samples from a peripheral vein and TTR sequencing. Transthoracic echocardiography.

Locations

Country	Name	City	State
Poland	Department of Cardiac and Vascular Diseases, John Paul II Hospital	Krakow	Lesser Poland

Sponsors (1)

Lead Sponsor	Collaborator
Katarzyna Holcman

Country where clinical trial is conducted

Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	left ventricle longitudinal strain	To investigate echocardiographic left ventricle longitudinal strain profile in hereditary and wild-type ATTR cardiac amyloidosis.	day 1
Primary	regional left ventricle 99mTc-DPD uptake	To compare the regional left ventricle 99mTc-DPD uptake among patients with hereditary and wild-type cardiac transthyretin amyloidosis.	day 1
Secondary	right ventricular 99mTc-DPD accumulation	To assess prevalence of right ventricular 99mTc-DPD accumulation among patients with hereditary and wild-type cardiac transthyretin amyloidosis.	day 1
Secondary	99mTc-DPD cardiac uptake among asymptomatic hereditary transthyretin amyloidosis variants carriers	To evaluate the presence and extent of 99mTc-DPD cardiac uptake among asymptomatic hereditary transthyretin amyloidosis variants carriers.	day 1