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

NCT06034405 | Recruiting DMC

• 2 other identifiers: AAAU4704R01AG081582-01
• Study Type: observational
• Target: 1,663
• Locations: 1 country
• Sites: 6

Brief 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. 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. 2.To evaluate for ATTR-CA among those with localized TTR in the spinal tissue.
3. 3.The prevalence of amyloid in lumbar spinal stenosis specimens by Congo Red staining.
4. 4.The prevalence of TTR deposits among subjects with amyloid as determined by mass spectrometry.
5. 5.Evaluation of a novel artificial intelligence technique for that can identify amyloid histologically with standard H\&E staining.
6. 6.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).

Conditions

Lumbar Spinal Stenosis; Cardiac Amyloidosis; ATTR Amyloidosis Wild Type; ATTR Gene Mutation; ATTRV122I Amyloidosis; Cardiomyopathy, Hypertrophic

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Percent of subjects with ATTR-CA among those with localized TTR in their spinal tissue

  up to 6 years

Study Arms (2)

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

Interventions

Tc99-PYP or Tc99-HDMP Scan DIAGNOSTIC_TEST

Difference in ATTR-CA prevalence between subjects with TTR and indeterminate amyloid deposits in their spine by myocardial uptake of Tc99-PYP.

ATTR Positive

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Previously procured surgical specimens from spinal surgery performed within 20 years prior to enrollment.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Columbia University: lead
• National Institute on Aging (NIA): collaborator

Study Sites (6)

Cedars-Sinai Medical Center

Beverly Hills, California, 90211, United States

RECRUITING

Tufts Medical Center

Boston, Massachusetts, 02111, United States

RECRUITING

Boston Medical Center

Boston, Massachusetts, 02359, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

ACTIVE NOT RECRUITING

Columbia University Irving Medical Center

New York, New York, 10032, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44195, United States

RECRUITING

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• Takeuchi M, Nishikage T, Mor-Avi V, Sugeng L, Weinert L, Nakai H, Salgo IS, Gerard O, Lang RM. Measurement of left ventricular mass by real-time three-dimensional echocardiography: validation against magnetic resonance and comparison with two-dimensional and m-mode measurements. J Am Soc Echocardiogr. 2008 Sep;21(9):1001-5. doi: 10.1016/j.echo.2008.07.008.

  PMID: 18765176 BACKGROUND

• Tendler A, Helmke S, Teruya S, Alvarez J, Maurer MS. The myocardial contraction fraction is superior to ejection fraction in predicting survival in patients with AL cardiac amyloidosis. Amyloid. 2015 Mar;22(1):61-6. doi: 10.3109/13506129.2014.994202. Epub 2014 Dec 16.

  PMID: 25510353 BACKGROUND

• Bokhari S, Castano A, Pozniakoff T, Deslisle S, Latif F, Maurer MS. (99m)Tc-pyrophosphate scintigraphy for differentiating light-chain cardiac amyloidosis from the transthyretin-related familial and senile cardiac amyloidoses. Circ Cardiovasc Imaging. 2013 Mar 1;6(2):195-201. doi: 10.1161/CIRCIMAGING.112.000132. Epub 2013 Feb 11.

  PMID: 23400849 BACKGROUND

• Cheng RK, Levy WC, Vasbinder A, Teruya S, De Los Santos J, Leedy D, Maurer MS. Diuretic Dose and NYHA Functional Class Are Independent Predictors of Mortality in Patients With Transthyretin Cardiac Amyloidosis. JACC CardioOncol. 2020 Sep;2(3):414-424. doi: 10.1016/j.jaccao.2020.06.007. Epub 2020 Sep 15.

  PMID: 33073249 BACKGROUND

• Lee JY, Moon SH, Suh BK, Yang MH, Park MS. Outcome and Complications in Surgical Treatment of Lumbar Stenosis or Spondylolisthesis in Geriatric Patients. Yonsei Med J. 2015 Sep;56(5):1199-205. doi: 10.3349/ymj.2015.56.5.1199.

  PMID: 26256960 BACKGROUND

• Kazi DS, Bellows BK, Baron SJ, Shen C, Cohen DJ, Spertus JA, Yeh RW, Arnold SV, Sperry BW, Maurer MS, Shah SJ. Cost-Effectiveness of Tafamidis Therapy for Transthyretin Amyloid Cardiomyopathy. Circulation. 2020 Apr 14;141(15):1214-1224. doi: 10.1161/CIRCULATIONAHA.119.045093. Epub 2020 Feb 12.

  PMID: 32078382 BACKGROUND

• Ruiz-Negron N, Nativi-Nicolau J, Maurer MS, Moran AE, Kovacsovics T, Bellows BK. Cost-effectiveness of technetium pyrophosphate scintigraphy versus heart biopsy for the diagnosis of transthyretin amyloidosis. Amyloid. 2019;26(sup1):71-72. doi: 10.1080/13506129.2019.1583192. No abstract available.

  PMID: 31343305 BACKGROUND

• Weintraub WS, Bhatt DL, Zhang Z, Dolman S, Boden WE, Bress AP, King JB, Bellows BK, Tajeu GS, Derington CG, Johnson J, Andrade K, Steg PG, Miller M, Brinton EA, Jacobson TA, Tardif JC, Ballantyne CM, Kolm P. Cost-effectiveness of Icosapent Ethyl for High-risk Patients With Hypertriglyceridemia Despite Statin Treatment. JAMA Netw Open. 2022 Feb 1;5(2):e2148172. doi: 10.1001/jamanetworkopen.2021.48172.

  PMID: 35157055 BACKGROUND

• Zhang Z, Kolm P, Grau-Sepulveda MV, Ponirakis A, O'Brien SM, Klein LW, Shaw RE, McKay C, Shahian DM, Grover FL, Mayer JE, Garratt KN, Hlatky M, Edwards FH, Weintraub WS. Cost-effectiveness of revascularization strategies: the ASCERT study. J Am Coll Cardiol. 2015 Jan 6;65(1):1-11. doi: 10.1016/j.jacc.2014.09.078.

  PMID: 25572503 BACKGROUND

• Zhang Z, Kolm P, Boden WE, Hartigan PM, Maron DJ, Spertus JA, O'Rourke RA, Shaw LJ, Sedlis SP, Mancini GB, Berman DS, Dada M, Teo KK, Weintraub WS. The cost-effectiveness of percutaneous coronary intervention as a function of angina severity in patients with stable angina. Circ Cardiovasc Qual Outcomes. 2011 Mar;4(2):172-82. doi: 10.1161/CIRCOUTCOMES.110.940502. Epub 2011 Feb 8.

  PMID: 21304091 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood will be drawn and analyzed for standard chemistry (Chem-7), liver function tests, NT-proBNP, troponin I and T, and TTR gene sequencing (see below). For subjects with ATTR-CA by positive uptake of 99mTc-PYP, further testing of prealbumin and monoclonal proteins (serum free light chains and immunofixation in serum and urine) will be performed. Additional aliquots will be stored at -80° for future analysis.

MeSH Terms

Conditions

Spinal Stenosis; Amyloid Neuropathies, Familial; Cardiomyopathy, Hypertrophic

Condition Hierarchy (Ancestors)

Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Amyloid Neuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Amyloidosis, Familial; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Amyloidosis; Proteostasis Deficiencies; Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Aortic Valve Disease; Heart Valve Diseases

Study Officials

• Mathew S Maurer, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mathew S Maurer, MD

CONTACT

212-932-4537; msm10@cumc.columbia.edu

Samantha L Guadalupe, MHA

CONTACT

212-932-4537; slg2172@cumc.columbia.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Arnold and Arlene Goldstein Professor of Cardiology (in Medicine, Dept of Medicine Cardiology)

Study Record Dates

• First Submitted: August 17, 2023
• First Posted: September 13, 2023
• Study Start: September 19, 2023
• Primary Completion: May 1, 2026
• Study Completion (Estimated): May 1, 2028
• Last Updated: November 12, 2025

Record last verified: 2025-11

Locations

US (6)