Screening for Systemic Amyloidosis Via the Ligamentum Flavum (ALF)

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ClinicalTrials.gov Identifier: NCT03923920

Recruitment Status : Recruiting

First Posted : April 23, 2019

Last Update Posted : April 30, 2020

See Contacts and Locations

Sponsor:

Information provided by (Responsible Party):

Mazen Hanna MD, The Cleveland Clinic

Study Description

Brief Summary:

The investigators will prospectively evaluate for the presence of amyloid deposits in ligamentum flavum (yellow ligament) tissue samples obtained from patients undergoing spinal stenosis surgery. Patients who have tissue that stains positive for amyloid will be referred to an amyloidosis specialist.

Condition or disease	Intervention/treatment
Amyloid Amyloidosis Spinal Stenosis Transthyretin Amyloidosis Primary Amyloidosis of Light Chain Type	Procedure: Biopsy

Detailed Description:

Similar to carpal tunnel syndrome, spinal stenosis is associated with systemic amyloidosis and presents earlier than cardiac amyloidosis symptoms - 21-45% of ATTR patients and case reports in AL patients. The investigators' recent study found that 10% of older patients undergoing carpal tunnel release surgery were positive for amyloidosis, with 20% of that group presenting with cardiac involvement. 70% of the amyloid-positive group had a history of spinal stenosis and 40% required surgical intervention. Surgical intervention for spinal stenosis could provide an opportunity to screen for amyloidosis through yellow ligament (ligamentum flavum) biopsy.

This study will look at the prevalence of amyloidosis in patients undergoing surgical intervention for non-congenital spinal stenosis and spondyloarthropathy. The investigators hypothesize that 10% of such patients will be positive for amyloidosis.

Study Design

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Study Type :	Observational
Estimated Enrollment :	200 participants
Observational Model:	Cohort
Time Perspective:	Prospective
Official Title:	Screening for Systemic Amyloidosis Via the Ligamentum Flavum
Actual Study Start Date :	May 1, 2019
Estimated Primary Completion Date :	April 1, 2021
Estimated Study Completion Date :	October 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Transthyretin amyloidosis

MedlinePlus related topics: Amyloidosis Biopsy Spinal Stenosis

Genetic and Rare Diseases Information Center resources: AL Amyloidosis Familial Transthyretin Amyloidosis

U.S. FDA Resources

Groups and Cohorts

Group/Cohort	Intervention/treatment
Spinal Stenosis Biopsy Biopsy of ligamentum flavum tissue during spinal stenosis surgery sent to pathology for amyloid-specific analysis	Procedure: Biopsy During clinically-scheduled spinal stenosis surgery, ligamentum flavum tissue (which may contain surrounding tissue and subcutaneous fat) that is removed during the procedure will be sent to pathology to be analyzed with amyloid-specific staining.

Outcome Measures

Primary Outcome Measures :

Incidence of amyloidosis in older patients undergoing spinal stenosis surgery [ Time Frame: Baseline to 30 days ]
Incidence of amyloid deposits in removed ligamentum flavum tissue of older patients undergoing spinal stenosis surgery

Biospecimen Retention: Samples With DNA

Ligamentum flavum tissue (may contain surrounding tissue and subcutaneous fat)

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	50 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Sampling Method:	Non-Probability Sample

Study Population

Patients undergoing spinal stenosis surgery

Criteria

Inclusion Criteria:

Age ≥50 years
Undergoing surgical intervention for non-congenital spinal stenosis and/or spondyloarthropathy
Able to consent

Exclusion Criteria:

History of congenital spinal stenosis or congenital spondyloarthropathy

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03923920

Contacts

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Contact: Mazen A Hanna, MD	2164443490	Hannam@ccf.org
Contact: Joseph P Donnelly, MD	3028932315	donnelj@ccf.org

Locations

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United States, Ohio
Cleveland Clinic	Recruiting
Cleveland, Ohio, United States, 44195
Contact: Mazen Hanna, M. D. 216-444-3490 hannam@ccf.org

Sponsors and Collaborators

The Cleveland Clinic

Investigators

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Principal Investigator:	Mazen A Hanna, MD	The Cleveland Clinic

More Information

Publications:

Sperry BW, Reyes BA, Ikram A, Donnelly JP, Phelan D, Jaber WA, Shapiro D, Evans PJ, Maschke S, Kilpatrick SE, Tan CD, Rodriguez ER, Monteiro C, Tang WHW, Kelly JW, Seitz WH Jr, Hanna M. Tenosynovial and Cardiac Amyloidosis in Patients Undergoing Carpal Tunnel Release. J Am Coll Cardiol. 2018 Oct 23;72(17):2040-2050. doi: 10.1016/j.jacc.2018.07.092.

Yanagisawa A, Ueda M, Sueyoshi T, Okada T, Fujimoto T, Ogi Y, Kitagawa K, Tasaki M, Misumi Y, Oshima T, Jono H, Obayashi K, Hirakawa K, Uchida H, Westermark P, Ando Y, Mizuta H. Amyloid deposits derived from transthyretin in the ligamentum flavum as related to lumbar spinal canal stenosis. Mod Pathol. 2015 Feb;28(2):201-7. doi: 10.1038/modpathol.2014.102. Epub 2014 Sep 5.

Westermark P, Westermark GT, Suhr OB, Berg S. Transthyretin-derived amyloidosis: probably a common cause of lumbar spinal stenosis. Ups J Med Sci. 2014 Aug;119(3):223-8. doi: 10.3109/03009734.2014.895786. Epub 2014 Mar 12.

Sueyoshi T, Ueda M, Jono H, Irie H, Sei A, Ide J, Ando Y, Mizuta H. Wild-type transthyretin-derived amyloidosis in various ligaments and tendons. Hum Pathol. 2011 Sep;42(9):1259-64. doi: 10.1016/j.humpath.2010.11.017. Epub 2011 Feb 21.

Sekijima Y, Yazaki M, Ueda M, Koike H, Yamada M, Ando Y. First nationwide survey on systemic wild-type ATTR amyloidosis in Japan. Amyloid. 2018 Mar;25(1):8-10. doi: 10.1080/13506129.2017.1409706. Epub 2017 Nov 28.

M'bappé P, Grateau G. Osteo-articular manifestations of amyloidosis. Best Pract Res Clin Rheumatol. 2012 Aug;26(4):459-75. doi: 10.1016/j.berh.2012.07.003. Review.

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Responsible Party:	Mazen Hanna MD, Principle Investigator, The Cleveland Clinic
ClinicalTrials.gov Identifier:	NCT03923920
Other Study ID Numbers:	18-1512
First Posted:	April 23, 2019 Key Record Dates
Last Update Posted:	April 30, 2020
Last Verified:	April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

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Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by Mazen Hanna MD, The Cleveland Clinic:


Biopsy Surgery Screening

Additional relevant MeSH terms:

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Immunoglobulin Light-chain Amyloidosis Spinal Stenosis Amyloidosis Proteostasis Deficiencies Metabolic Diseases Spinal Diseases Bone Diseases Musculoskeletal Diseases	Neoplasms, Plasma Cell Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Immunoproliferative Disorders Immune System Diseases Paraproteinemias

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