Orthopaedic Specimen Pathology and Early Diagnosis of ATTR Cardiopathy (ATTR-ORTHO) (ATTR-ORTHO)

Contribution of Systematic Pathological Examination of Orthopaedic Specimens to the Early Diagnosis of Tranthyretin Amyloid Heart Disease

The goal of this observational study is to learn about the frequency of ATTR amyloid, cardiac involvement and associated features, in 150 patients aged 50 or more years, and operated for an idiopathic carpal tunnel syndrome, lumbar spine stenosis or total hip or knee arthroplasty for primary osteoarthritis. The main questions to be answered are:

1. What is the frequency of ATTR deposits in samples retrieved during surgery?
2. What is the frequency of cardiac involvement in ATTR positive patients?

3. What are the preoperative predictors of ATTR deposits? Participants will

   • have operative samples stained by Congo red in search of amyloid, which will be typed by immunochemistry in positive samples,
   • undergo a multimodal imaging search for cardiac involvement, if ATTR is identified,
   • undergo a preoperative complete clinical examination, including collection of medical history, ECG, biochemical tests, and imaging (ultrasound scans of rotator cuff and hip capsule in all participating patients, of the carpal tunnel in patients operated at this site, and MRI + standing profile radiography of the lumbar spine, in patients operated for lumbar stenosis)
   • ATTR positive patients will be proposed to be followed-up by a reference center, with the aim of an early diagnosis of cardiac involvement, allowing efficient mamagement.

Researchers will assess the frequency of ATTR deposits at each operated site, the frequency or ATTR cardiopathy in ATTR + patients, and will compare demographic, clinical, biochemical, and imaging features in patients with and without ATTR deposits, to guide the indications of pathological examination during these frequent orthopedic surgeries

Study Overview

• Status: Recruiting
• Conditions: Carpal Tunnel Syndrome; Knee Prosthesis; ATTR Amyloidosis; Cardiopathy; Hip Prosthesis; Lumbar Spine Stenosis

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

Study Locations

• France
  • Paris, France, 75014
    • Recruiting
    • Mutualist Montsouris Institute
    • Contact: Thomas M Bardin, Pr; Phone Number: +33 156616263; Email: thomas.bardin@imm.fr

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

Patients meeting the inclusion criteria in a single orthopaedic surgery center located in Paris, France

Description

Inclusion Criteria:

1. patients aged 50 or over
2. having signed an informed consent form

3. undergoing surgery for

   1. idiopathic carpal tunnel syndrome
   2. or lumbar spinal canal stenosis
   3. or prosthetic replacement of a hip or knee for primary osteoarthritis

Exclusion Criteria:

1. secondary carpal tunnel syndrome (inflammatory rheumatism, diabetes, hypothyroidism, etc.)
2. Indication of prosthesis for a condition other than primary osteoarthritis.
3. Known amyloidosis
4. Refusal of consent
5. Inability to understand the study
6. Age < 50 years

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
frequency of ATTR amyloidosis	presence of ATTR amyloidosis in surgical samples by immunohistochemistry performed when samples countain amyloi by Congo red.ATTR will be semiquantitalively assessed using a published scale.	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
presence of ATTR cardiopathy	Diagnosis by multimodal imaging(bone scintigraphy, cardiac US scan, MRI)	20 months
proportion of wild type and hereditary ATTR	hereditary: patients exibit a mutation of the TTR gene, wild type: no mutation. TTR genotyping will determine if the gene is muted (hereditary ATTR) or not (wild type).	20 months
Description of preoperative predictors of ATTR	features more frequent in patients diagnosed with ATTR versus not: - demographic and clinical characteristics, will be collected before surgery and compared in ATTR positive and ATTR negative patients.	18 months
Description of preoperative predictors of ATTR	features more frequent in patients diagnosed with ATTR versus not: - imaging characteristics (USscans of rotator cuff, hip capsula and carpal tunel) will be collected before surgery and compared in ATTR positive and ATTR negative patients.	18 months
preoperative predictors of ATTR	biochemical features more frequent in patients diagnosed with ATTR versus not: troponine (g/L); BNP (ng/L); proteuniria (ng/L) will be collected before surgery and compared in ATTR positive and ATTR negative patients.	18 months

Collaborators and Investigators

• Sponsor: Institut Mutualiste Montsouris

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2024
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: March 6, 2024
• First Submitted That Met QC Criteria: April 10, 2024
• First Posted (Actual): April 16, 2024

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: orthopaedic surgery; cardiac amyloidosis; ATTR amyloidosis
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Metabolic Diseases; Nervous System Diseases; Wounds and Injuries; Neuromuscular Diseases; Mononeuropathies; Peripheral Nervous System Diseases; Median Neuropathy; Nerve Compression Syndromes; Cumulative Trauma Disorders; Sprains and Strains; Proteostasis Deficiencies; Heart Diseases; Carpal Tunnel Syndrome; Amyloidosis
• Other Study ID Numbers: MED-02-2023

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No