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

March 19, 2024 updated by: Mathew S. Maurer, MD, Columbia University

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Observational

Enrollment (Estimated)

1663

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • California
      • Beverly Hills, California, United States, 90211
        • Recruiting
        • Cedars-Sinai Medical Center
        • Contact:
        • Contact:
        • Principal Investigator:
          • Jignesh Patel, MD
        • Sub-Investigator:
          • Michelle Kittleson, MD,PhD
    • Massachusetts
      • Boston, Massachusetts, United States, 02111
      • Boston, Massachusetts, United States, 02359
        • Recruiting
        • Boston Medical Center
        • Contact:
        • Contact:
        • Principal Investigator:
          • Frederick Ruberg, MD
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Active, not recruiting
        • Mayo Clinic
    • New York
      • New York, New York, United States, 10032
        • Recruiting
        • Columbia University Irving Medical Center
        • Principal Investigator:
          • Mathew S Maurer, MD
        • Contact:
        • Contact:
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic
        • Contact:
        • Contact:
          • Lauren Ives, RN
          • Phone Number: 216-316-3370
          • Email: ivesl@ccf.org
        • Principal Investigator:
          • Mazen Hanna, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Probability Sample

Study Population

Previously procured surgical specimens from spinal surgery performed 5 to 15 years ago.

Description

Inclusion Criteria:

  1. Clinically indicated lumbar spinal decompressive surgery that involved removal of the ligamentum flavum 5 to 15 years prior to enrollment.
  2. Age >60 years at the time of the surgery.
  3. Able to understand and sign the informed consent document after the nature of the study has been fully explained.

Exclusion Criteria:

  1. Confirmed primary amyloidosis (AL) or secondary amyloidosis (AA).
  2. Known TTR amyloidosis.
  3. Lumbar surgery for indications other than spinal stenosis.
  4. Active malignancy.
  5. Impairment from stroke, injury or other medical disorder that precludes participation in the study.
  6. Disabling dementia or other mental or behavioral disease.
  7. Enrollment in a clinical trial not approved for co-enrollment.
  8. Weight >350 lbs.
  9. Inability or unwillingness to comply with the study requirements.
  10. Nursing home resident.
  11. Other reason that would make the subject inappropriate for entry into this study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
ATTR Negative
Participants who have undergone previous lumbar spinal, and/or carpel tunnel surgery will provide medical record data and spinal specimen for analysis of presence of ATTR amyloid.
ATTR Positive
Participants who have undergone previous lumbar spinal, and/or carpel tunnel surgery will provide medical record data, spinal specimen, prospective data from cardiac workup with confirmed ATTR amyloid in spinal specimen then undergo cardiac workup for cardiac phenotyping/genotyping.
Diagnostic test: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: up to 3 years
To identify who can be at risk for ATTR Cardiac Amyloidosis. The investigator is going to collect spinal ligamentum flavum specimens and stain with congo red and those who result positive for ATTR amyloid in their spinal specimen will be counted
up to 3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent of subjects with ATTR-CA among those with localized TTR in their spinal tissue
Time Frame: up to 6 years
To evaluate number of subjects with ATTR-CA among those with localized TTR in their spinal tissue. The investigator is going to perform standard of care (SOC) cardiac amyloidosis work up including PYP scan to confirm cardiac phenotype
up to 6 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Columbia University

Collaborators

National Institute on Aging (NIA)

Investigators

  • Principal Investigator: Mathew S Maurer, MD, Columbia University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 19, 2023

Primary Completion (Estimated)

May 1, 2025

Study Completion (Estimated)

May 1, 2028

Study Registration Dates

First Submitted

August 17, 2023

First Submitted That Met QC Criteria

September 5, 2023

First Posted (Actual)

September 13, 2023

Study Record Updates

Last Update Posted (Actual)

March 20, 2024

Last Update Submitted That Met QC Criteria

March 19, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AAAU4704
  • R01AG081582-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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