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

Amyloidosis Clinical Trial

Official title:

A PILOT Study on Labial Salivary Gland Biopsy Potentially to Replace Endomyocardial Biopsy in the Diagnosis of Cardiac Transthyretin Amyloidosis

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05375279
• Other study ID #: 70095215
• Status: Not yet recruiting
• Start date: June 15, 2022
• Est. completion date: March 31, 2023

Study information

• Verified date: May 2022
• Source: Unity Health Toronto
• Contact: Gordon W. Moe, MD, FRCPC, FACC
• Phone: 416-864-5192
• Email: Gordon.Moe[@]unityhealth.to
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: March 31, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 96 Years

Eligibility

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.

Related Conditions & MeSH terms

• Amyloidosis

Intervention

Procedure:
• Lip Salivary Gland Biopsy
Obtaining few salivary glands from the partipants' lip that will be studied using the Congo Red staining method.

Locations

Country	Name	City	State
Canada	London Health Sciences Centre	London	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Unity Health Toronto	Pfizer

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	LSG biopsy with positive amyloid deposits will be observed in a higher proportion in patients with positive EMB.	Proportions of patients who will test positive and negative will be determined.	6 months