Analysis of Lumbar Spine Stenosis Specimens for Identification of Transthyretin Cardiac Amyloidosis

Обзор

Primary objective: To identify older adults with transthyretin cardiac amyloidosis (ATTR-CA) early in the course of the illness, at a time when disease modifying therapies are most effective. The specific aims of this epidemiologic investigation include: 1. To identify subjects with previous lumbar spinal stenosis (LSS) Surgery who have evidence of transthyretin (TTR) amyloid deposits in spinal specimens and could be at risk for ATTR cardiac amyloidosis. 2. To evaluate for ATTR-CA among those with localized TTR in the spinal tissue. The study will also explore the following: 1. The prevalence of amyloid in lumbar spinal stenosis specimens by Congo Red staining. 2. The prevalence of TTR deposits among subjects with amyloid as determined by mass spectrometry. 3. Evaluation of a novel artificial intelligence technique for that can identify amyloid histologically with standard H\&E staining. 4. Difference in ATTR-CA prevalence between subjects with TTR and indeterminate amyloid deposits in subject's spine by myocardial uptake of technetium pyrophosphate scan (Tc99-PYP).

Подробное описание

This is a multicenter, prospective cohort study aimed at facilitating identification of individuals with ATTR-CA. Investigators will identify subjects with previous LSS surgery who have evidence of TTR amyloid deposits in spinal specimens. Subjects with localized TTR in spinal tissue will be invited to an on-site visit and be evaluated for the presence of clinical manifestations of ATTR cardiac amyloidosis (ATTR-CA).

Subjects will undergo nuclear scintigraphy, TTR genetic test, a clinical evaluation, electrocardiogram, and echocardiogram. Quality of life questionnaires will also be administered. Subjects who have myocardial retention of the imaging radiotracer with a Perugini score equal to 2 (uptake equal to bone) or 3 (uptake greater than bone) and confirmation by SPECT or SPECT/CT that the uptake is myocardial in nature and have no evidence of monoclonal proteins will be diagnosed with ATTR-CA.

This study is to be conducted at five study sites: Boston Medical Center, Cedars Sinai Medical Center, Cleveland Clinic, Columbia University Irving Medical Center, and Tufts University Medical Center. The Mayo Clinic will serve a Pathology research core to analyze spine specimens.

Most of the subjects are expected to complete all the study procedures and questionnaires on a single day.

Up to 1663 patients will be consented in this study to have spinal specimens examined for the presence of amyloid by Congo Red at the Mayo Clinic core lab. From the pool of subjects with amyloid detected (which anticipate will be 33% or at least 544), the investigators expect to recruit 163 participants to undergo cardiac phenotyping (Tc99m and cardiac evaluation). Among the 163 participants who undergo cardiac phenotyping, 98 will have TTR as the precursor protein identified by mass spectrometry and 65 will have an indeterminant precursor protein by mass spectrometry.

Вмешательства

• Диагностический тест Tc99-PYP or Tc99-HDMP Scan
  Difference in ATTR-CA prevalence between subjects with TTR and indeterminate amyloid deposits in their spine by myocardial uptake of Tc99-PYP.

Первичные конечные точки

• Percent of subjects with previous LSS surgery who have evidence of TTR amyloid deposits in their spinal specimen and could be at risk for ATTR cardiac amyloidosis [Срок оценки: up to 3 years]

Вторичные конечные точки (1)

• Percent of subjects with ATTR-CA among those with localized TTR in their spinal tissue [Срок оценки: up to 6 years]

Критерии участия

Критерии включения

• Clinically indicated spinal decompressive surgery within 20 years prior to enrollment.
• Age ≥50 years at the time of the surgery.
• Able to understand and sign the informed consent document after the nature of the study has been fully explained.

Критерии исключения

The presence of any of the following excludes eligibility for enrollment in this study:

• Confirmed primary amyloidosis (AL) or secondary amyloidosis (AA).
• Known TTR amyloidosis.
• Other reason that would make the subject inappropriate for entry into this study.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

США · 6 центров

• Cedars-Sinai Medical Center — Beverly Hills
• Tufts Medical Center — Boston
• Boston Medical Center — Boston
• Mayo Clinic — Rochester
• Columbia University Irving Medical Center — New York
• Cleveland Clinic — Cleveland

Публикации

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• Maurer MS, Schwartz JH, Gundapaneni B, Elliott PM, Merlini G, Waddington-Cruz M, Kristen AV, Grogan M, Witteles R, Damy T, Drachman BM, Shah SJ, Hanna M, Judge DP, Barsdorf AI, Huber P, Patterson TA, Riley S, Schumacher J, Stewart M, Sultan MB, Rapezzi C; ATTR-ACT Study Investigators. Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy. N Engl J Med. 2018 Sep 13;379(11):1007 PMID 30145929
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Идентификаторы

NCT: NCT06034405 · AAAU4704 · R01AG081582-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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