Carpal Tunnel Syndrome and Amyloid Cardiomyopathy

The investigators will prospectively evaluate tissue samples obtained from patients undergoing carpal tunnel release surgery for amyloid in the soft tissue that is removed. Patients who have tissue that stains positive for amyloid will undergo cardiac testing to look for evidence of cardiac involvement.

Study Overview

• Status: Completed
• Conditions: Carpal Tunnel Syndrome; Amyloidosis; Transthyretin Amyloidosis; Cardiomyopathy; Senile Systemic Amyloidosis

Detailed Description

Since the 1970s, the connection between amyloidosis and carpal tunnel syndrome has been described, with tenosynovial tissue staining positive for amyloid fibril deposition. Up to 30% of patients in prior studies with idiopathic carpal tunnel syndrome have biopsy tissue that stains positive for amyloid deposition. However, the prevalence of cardiac involvement at the time of carpal tunnel syndrome surgery has not been established. Furthermore, the role of TTR kinetic stability in the disease progression of amyloidosis is unclear.

Diagnosing TTR amyloidosis at the time of carpal tunnel involvement could lead to an earlier identification of the disease at a stage where the cardiomyopathy may be occult or less advanced. In addition, abnormal TTR kinetics may even precede tissue deposition in the flexor tendon retinaculum. As several emerging pharmacological strategies are in development that may slow or even halt TTR amyloidosis, earlier diagnosis is advantageous. Identification and implementation of therapy for prevention or early disease treatment may alter the natural history of this progressive systemic disease.

• Study Type: Observational
• Enrollment (Actual): 96

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44113
      • Lutheran Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adult patients undergoing carpal tunnel release surgery for idiopathic carpal tunnel syndrome not responding conservative and medical management.

Description

Inclusion Criteria:

• Males ≥ 50 years of age
• Females ≥ 60 years of age
• Undergoing carpal tunnel release surgery (adequate symptoms are not responding to conservative management requiring surgery)
• Able to consent
• Underwent carpal tunnel surgery and biopsy within last 30 days, if the study was discussed prior to surgery by one of the study physicians.

Exclusion Criteria:

• Secondary CTS (Hemodialysis, rheumatoid arthritis, trauma)
• Known diagnosis of amyloidosis

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Patients with carpal tunnel syndrome.; Patients undergoing carpal tunnel release surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of transthyretin (TTR) amyloidosis in patients undergoing carpal tunnel release surgery	Identify the incidence of TTR amyloid deposits in the soft tissue of patients undergoing carpal tunnel surgery for idiopathic carpal tunnel syndrome	Biopsy completed on day of surgery
Cardiac progression of transthyretin (TTR) amyloidosis in carpal tunnel biopsy-positive patients	Assess the progression of cardiac disease in patients with TTR deposits found in soft tissue removed at the time of carpal tunnel surgery	4 years from baseline cardiac assessment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of abnormal transthyretin (TTR) kinetics in patients undergoing carpal tunnel surgery	Identify the prevalence of abnormal TTR kinetics in patients undergoing carpal tunnel surgery for idiopathic carpal tunnel syndrome (develop a new test that aids identification of misfolded TTR intermediates that is more specific and sensitive to diagnosis this disease in the blood or tissue)	One-time kinetics test for biopsy-negative patients; baseline kinetics and annually for 4 years in biopsy-positive patients
Early transthyretin (TTR) amyloid cardiomyopathy identification in carpal tunnel biopsy-positive patients	Investigate whether early TTR cardiomyopathy can be identified in patients who have TTR amyloid deposits identified in the soft tissue removed at the time of carpal tunnel surgery using cardiac biomarkers, echocardiography with strain, and nuclear bone scintigraphy	Baseline and annual testing for 4 years in biopsy-positive patients

Collaborators and Investigators

• Sponsor: The Cleveland Clinic
• Investigators: Principal Investigator: Mazen Hanna, MD, The Cleveland Clinic

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2016
• Primary Completion (Actual): July 21, 2021
• Study Completion (Actual): December 2, 2021

Study Registration Dates

• First Submitted: April 20, 2016
• First Submitted That Met QC Criteria: June 2, 2016
• First Posted (Estimate): June 8, 2016

Study Record Updates

• Last Update Posted (Actual): December 22, 2021
• Last Update Submitted That Met QC Criteria: December 21, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Amyloidosis; Carpal tunnel syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Metabolic Diseases; Nervous System Diseases; Wounds and Injuries; Disease; Neuromuscular Diseases; Mononeuropathies; Peripheral Nervous System Diseases; Median Neuropathy; Nerve Compression Syndromes; Cumulative Trauma Disorders; Sprains and Strains; Proteostasis Deficiencies; Syndrome; Carpal Tunnel Syndrome; Amyloidosis; Cardiomyopathies
• Other Study ID Numbers: 16-158

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No