Early Diagnosis of Age-Linked CArdiac TransThyRetin Amyloidosis by Selective Screening in Spinal Stenosis Surgery (ALCATTRASS)

Early Diagnosis of Age-Linked CArdiac TransThyRetin Amyloidosis by Selective Screening in Spinal Stenosis Surgery: the Multi-centric ALCATTRASS-study.

The goal of this observational study is to keep track of the cardiological follow-up of patients who have undergone back surgery because of symptomatic narrowing of the spinal canal and in whom microscopic examination of the tissue removed during this surgery showed a high amount of local deposits of small proteins. This finding may be an early sign of a condition in which other organs (especially the heart) may also be affected by these proteins, called amyloidosis.

Patients who participate in this study, will be followed up for life. During the first routine consultation with the cardiologist, the physician-investigator will collect information, such as demographics (age, weight, height, gender), medical history, medication, symptoms and the results of prescribed examinations. These examinations include microscopic examination of tissue removed during the surgery, blood tests, electrocardiography, echocardiography and a bone scan. These examinations are clinically necessary and appropriate, and patients should undergo them even without participating in the study.

Study Overview

• Status: Recruiting
• Conditions: Transthyretin Amyloid Cardiomyopathy

Detailed Description

Background: Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed, severe, yet treatable disease. Lumbar spinal stenosis (SS) in elderly is a red flag for ATTR-CM, often preceding cardiac diagnose by many years. Yet, optimal screening strategies for early ATTR-CM detection at time of SS diagnosis are underused.

Study aim: Multi-centric validation of the diagnostic yield of a standard-of-care prospective screening strategy for early ATTR-CM detection in the elderly, based on ligamentum flavum biopsy assessment at SS surgery.

Design: International, multi-centre, prospective, observational, multi-disciplinary, diagnostic registry.

Methods: All consecutive patients ≥60 years old undergoing standard-of-care ligamentum flavum biopsy as part of symptomatic SS surgery within 12 heart centres are included. The burden of ATTR amyloid deposition (positive Congo-red and pre-albumin staining) is assessed semi-quantitatively by visual Westermark grading. Patients with significant ATTR amyloid burden (grade 3 (≥5-10%) or 4 (>10%) ATTR amyloid on biopsy specimen) undergo standard-of-care work-up to exclude ATTR-CM, conform state-of-the-art clinical practice and ESC recommendations (i.e. baseline cardiac biomarkers, ECG, transthoracic echocardiography, monoclonality assessment and bone-scintigraphy with SPECT; additional CMR and/or endomyocardial biopsy as needed). The diagnostic yield of this biopsy-based strategy will be evaluated.

Conclusion: This trial will validate the diagnostic yield of selective ligamentum flavum biopsy analysis in SS surgery patients as a simple and valuable prospective screening strategy for early ATTR-CM detection.

• Study Type: Observational
• Enrollment (Estimated): 400

Contacts and Locations

• Study Contact: Name: Emma Christiaen; Phone Number: 0032 50 45 32 93; Email: emma.christiaen@azsintjan.be

Study Locations

• Belgium
  • Brugge, Belgium
    • Recruiting
    • AZ Sint-Jan Brugge AV
    • Contact: Philippe Debonnaire

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

All consecutive patients ≥60 years old that undergo lumbar spinal stenosis surgery at the neurosurgery or orthopaedic department with Westermark grade 3 or 4 ATTR amyloid burden on ligamentum flavum biopsy

Description

Inclusion Criteria:

• ≥ 60 years old
• Lumbar spinal canal stenosis, undergoing spinal surgery
• Westermark grade 3 or 4 ATTR amyloid burden on ligamentum flavum biopsy

Exclusion Criteria:

• Prior diagnosis of cardiac amyloidosis
• Unwilling to provide informed consent

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of diagnosis of cardiac amyloidosis	Diagnosis of transthyretin amyloid cardiomyopathy	1 week

Collaborators and Investigators

• Sponsor: Philippe Debonnaire
• Investigators: Principal Investigator: Philippe Debonnaire, MD, PhD, AZ Sint-Jan Brugge AV

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: October 20, 2023
• First Submitted That Met QC Criteria: October 20, 2023
• First Posted (Actual): October 26, 2023

Study Record Updates

• Last Update Posted (Actual): August 7, 2024
• Last Update Submitted That Met QC Criteria: August 6, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Metabolic Diseases; Musculoskeletal Diseases; Proteostasis Deficiencies; Spinal Diseases; Bone Diseases; Amyloidosis; Cardiomyopathies; Spinal Stenosis
• Other Study ID Numbers: ALCATTRASS

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