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

Lumbar Spinal Stenosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06034405
• Other study ID #: AAAU4704
• Secondary ID: R01AG081582-01
• Status: Recruiting
• Start date: September 19, 2023
• Est. completion date: May 2028

Study information

• Verified date: March 2024
• Source: Columbia University
• Contact: Mathew S Maurer, MD
• Phone: 212-932-4537
• Email: msm10[@]cumc.columbia.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1663
• Est. completion date: May 2028
• Est. primary completion date: May 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 60 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Amyloidosis
• Cardiac Amyloidosis
• Cardiomyopathies
• Cardiomyopathy, Hypertrophic
• Constriction, Pathologic
• Lumbar Spinal Stenosis
• Spinal Stenosis

Intervention

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.

Locations

Country	Name	City	State
United States	Cedars-Sinai Medical Center	Beverly Hills	California
United States	Boston Medical Center	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	Cleveland Clinic	Cleveland	Ohio
United States	Columbia University Irving Medical Center	New York	New York
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Columbia University	National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

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* Note: There are 64 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	Percent of subjects with ATTR-CA among those with localized TTR in their spinal tissue	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