Clinical trial NCT05375279: A PILOT Study on LSGB vs EMB in the Diagnosis of Cardiac Transthyretin Amyloidosis
Official title: A PILOT Study on Labial Salivary Gland Biopsy Potentially to Replace Endomyocardial Biopsy in the Diagnosis of Cardiac Transthyretin Amyloidosis
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Amyloidosis
Keywords: Amyloidosis
Cardiomyopathy
Lead sponsor: Unity Health Toronto
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2022-05-16
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 96
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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).

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.

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.

Primary outcomes:
measure: LSG biopsy with positive amyloid deposits will be observed in a higher proportion in patients with positive EMB.
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
Study officials:
affiliation: Unity Health Toronto
name: Gordon W Moe, MD, FRCPC, FACC
role: PRINCIPAL_INVESTIGATOR
References: