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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Amyloidosis
• Intervention / Treatment: Procedure: Lip Salivary Gland Biopsy

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.

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

Contacts and Locations

• Study Contact: Name: Gordon W. Moe, MD, FRCPC, FACC; Phone Number: 416-864-5192; Email: Gordon.Moe@unityhealth.to
• Study Contact Backup: Name: Carlos Fernando, MD, MSc, MBA; Phone Number: 46969 416-864-6060; Email: Carlos.Fernando@unityhealth.to

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Centre
      • Contact: Heather Hern; Phone Number: 32818 519-685-8500; Email: heather.hern@lhsc.on.ca
      • Principal Investigator: Ryan Davey, MD, FRCPC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 96 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

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).

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
LSGB vs EMB; Patients who already underwent EMB within the last six months with confirmed Amyloid Transthyretin -wild type (ATTRwT) will undergo LSGB.	Procedure: Lip Salivary Gland Biopsy; Obtaining few salivary glands from the partipants' lip that will be studied using the Congo Red staining method.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Unity Health Toronto
• Collaborators: Pfizer
• Investigators: Principal Investigator: Gordon W Moe, MD, FRCPC, FACC, Unity Health Toronto

Study record dates

Study Major Dates

• Study Start (Anticipated): June 15, 2022
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): March 31, 2023

Study Registration Dates

• First Submitted: May 10, 2022
• First Submitted That Met QC Criteria: May 10, 2022
• First Posted (Actual): May 16, 2022

Study Record Updates

• Last Update Posted (Actual): May 23, 2022
• Last Update Submitted That Met QC Criteria: May 16, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Amyloidosis; Cardiomyopathy
• Additional Relevant MeSH Terms: Metabolic Diseases; Proteostasis Deficiencies; Amyloidosis
• Other Study ID Numbers: 70095215

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No