A PILOT Study on LSGB vs EMB in the Diagnosis of Cardiac Transthyretin Amyloidosis

NCT ID: NCT05375279

Last Updated: 2022-05-23

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 20 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-06-15
• Study Completion Date: 2023-03-31

Brief Summary

Transthyretin (TTR) is a plasma protein mainly synthesized in the liver, recognized as a transporter of thyroxine and retinol-binding protein. Unstable changes in two types of TTR (wild type or variant) become misfolded, aggregate, and ultimately forms amyloid fibrils. Amyloid Transthyretin Cardiac amyloidosis (ATTR-CA) is an infiltrative cardiomyopathy caused by extracellular deposition of insoluble transthyretin (TTR) amyloid fibrils in the heart muscle. Cardiac amyloidosis (CA) has been recognized as a common cause of heart failure with preserved ejection fraction (HFpEF) among elderly persons, with increasing incidence.

There are different ways of diagnosing ATTR-CA. These include cardiac magnetic resonance imaging, nuclear scintigraphy, and tissue biopsy, the gold standard. Tissues biopsy extracted from the adipose, lip salivary gland (LSG), and heart muscle (endomyocardial biopsy or EMB).

Tissue diagnosis is the prerequisite of provincial support of the disease-modifying agent. However, with the convenience, ease, less risk of bleeding, and high sensitivity, LSG may offer an alternative to the more invasive EMB to diagnose suspected CA.

To test the hypothesis that LSGB can replace EMB in tissue diagnosis of ATTR-CM.

This Pilot study is designed to evaluate two invasive diagnostic methodologies: LSGB and the EMB. A total of 20 patients who underwent EMB within the last six months with confirmed Amyloid Transthyretin -wild type (ATTRwT) will be invited to participate. In addition, patients who signed the informed consent form will be scheduled for LSGB within two weeks.

Detailed Description

We propose broad eligibility criteria to increase the generalizability and feasibility of the proposed study. Patients who are confirmed diagnosis of Amyloid Transthyretin Cardiomyopathy - wild type (ATTRwt) through Echocardiography, Cardiac Magnetic Resonance Imaging, pyrophosphate scan, and genetic testing and had an endomyocardial biopsy (or will undergo endomyocardial biopsy) are eligible to participate in the study.The exclusion criteria are predominantly patients who had negative amyloid deposits in the endomyocardial biopsy. There are no exclusions based on gender, race or ethnicity in this trial.

LSG biopsy will be performed under local anesthesia (2% lidocaine). The lip will be everted, and a 3 to 4 mm longitudinal incision will be made in the labial mucosa in front of the mandibular canine tooth. Three minor salivary glands will be exposed and removed. No silk suture will be used. [18] The LSG specimen will match the EMB specimen. LSG biopsy tissues will be studied using the method of Congo red stain.[18] The participants will be scheduled for LSGB at the London Health Sciences Centre within two weeks of signing the informed consent.

Conditions

Amyloidosis

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

LSGB vs EMB

Patients who already underwent EMB within the last six months with confirmed Amyloid Transthyretin -wild type (ATTRwT) will undergo LSGB.

Lip Salivary Gland Biopsy

Intervention Type: PROCEDURE

Obtaining few salivary glands from the partipants' lip that will be studied using the Congo Red staining method.

Interventions

Lip Salivary Gland Biopsy

Obtaining few salivary glands from the partipants' lip that will be studied using the Congo Red staining method.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Patients who are confirmed diagnosis of Amyloid Transthyretin Cardiomyopathy - wild type (ATTRwt) through Echocardiography, Cardiac Magnetic Resonance Imaging, pyrophosphate scan, and genetic testing and had an endomyocardial biopsy (or will undergo endomyocardial biopsy).

Exclusion Criteria

• Patients who had negative amyloid deposits in the endomyocardial biopsy.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 96 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

Unity Health Toronto

OTHER

Sponsor Role: lead

Responsible Party

Gordon Moe

Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gordon W Moe, MD, FRCPC, FACC

Role: PRINCIPAL_INVESTIGATOR

Unity Health Toronto

Locations

London Health Sciences Centre

London, Ontario, Canada

Countries

Canada

Central Contacts

Gordon W. Moe, MD, FRCPC, FACC

Role: CONTACT

Gordon.Moe@unityhealth.to

416-864-5192

Carlos Fernando, MD, MSc, MBA

Role: CONTACT

Carlos.Fernando@unityhealth.to

416-864-6060 ext. 46969

Facility Contacts

Heather Hern

Role: primary

heather.hern@lhsc.on.ca

519-685-8500 ext. 32818

Other Identifiers

70095215

Identifier Type: -

Identifier Source: org_study_id