Evaluation of DNA Methylation Signatures for the Diagnosis and Management of Thyroid Nodules

February 20, 2026 updated by: City of Hope Medical Center

Evaluation of DNA Methylation Signatures in Diagnosis and Management of Thyroid Nodules

This clinical trial evaluates deoxyribonucleic acid (DNA) methylation signatures in diagnosing and managing thyroid nodules. The purpose of this research is to develop a new test for thyroid cancer. This test will use needle biopsies (small collections of tissue with a needle) from the thyroid to determine whether the participant has a malignant (cancer) or benign (not showing cancer) thyroid tumor. The information learned from this trial may help develop a more accurate test so that patients do not have unnecessary surgeries for nodules that are thought to be suspicious but are actually benign.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVE:

I. To evaluate the effect of Diagnostic DNA Methylation Signatures (DDMS-2) results (positive predictive value [PPV], negative predictive value [NPV], sensitivity and specificity) on physician decision-making for clinical management of 800 indeterminate thyroid nodules.

SECONDARY OBJECTIVES:

I. To determine sensitivity and specificity, PPV, NPV of DDMS-2 with 1450 needle biopsies including 800 needle biopsies with indeterminate cytopathology.

II. Compare the diagnostic accuracy between DDMS-2 and two currently used diagnostic approaches based on genetic alterations and gene expression within the same prospective cohort of 800 indeterminate needle biopsies.

OUTLINE:

Patients undergo needle biopsy for collection of tissue samples. Tissue samples are analyzed using DDMS-2. Patients' medical records are also reviewed.

Study Type

Interventional

Enrollment (Estimated)

1450

Phase

  • Not Applicable

Contacts and Locations

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

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope Medical Center
        • Contact:
          • John H. Yim
          • Phone Number: 626-218-3590
          • Email: JYim@coh.org
        • Principal Investigator:
          • John H. Yim

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients without impaired decision-making capacity and who are undergoing needle biopsies for thyroid nodule diagnosis
  • Over the age of 18
  • Any gender, race and ethnicity
  • Patients must provide informed consent prior to use of their tissues and clinical data

Exclusion Criteria:

  • Children are excluded from the study, since the biology of children thyroid nodules is different from adults

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

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Diagnostic (needle biopsy, DDMS-2)
Patients undergo needle biopsy for collection of tissue samples. Tissue samples are analyzed using DDMS-2. Patients' medical records are also reviewed.
Other: Electronic Health Record Review
Review of medical records
Procedure: Diagnostic Procedure
Analysis via DDMS-2
Other Names:
  • Diagnostic Method
  • Diagnostic Technique
  • Diagnostic Test
Procedure: Needle Biopsy
Undergo needle biopsy
Other Names:
  • Aspiration Biopsy
  • Puncture Biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sensitivity of Diagnostic Deoxyribonucleic Acid (DNA) Methylation Signatures (DDMS-2)
Time Frame: Up to 5 years
The sensitivity of DDMS-2 will be estimated by taking the ratio of the number of true thyroid cancer specimens diagnosed as cancer by DDMS and the total number of thyroid cancer specimens. Will also determine the 95% confidence intervals.
Up to 5 years
Specificity of DDMS-2
Time Frame: Up to 5 years
The specificity will be estimated by taking the ratio of the number of true benign nodules diagnosed as benign by DDMS and the total number of true benign thyroid nodules. Will also determine the 95% confidence intervals.
Up to 5 years
Positive predictive value (PPV) of DDMS-2
Time Frame: Up to 5 years
PPV (number of true thyroid cancer specimens by DDMS / number of thyroid cancers diagnosis by DDMS) will be calculated. Will also determine the 95% confidence intervals.
Up to 5 years
Negative predictive value (NPV) of DDMS-2
Time Frame: Up to 5 years
NPV (number of true benign nodules diagnosed by DDMS/number of benign diagnosis by DDMS) will be calculated. Will also determine the 95% confidence intervals.
Up to 5 years

Collaborators and Investigators

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

Sponsor

City of Hope Medical Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: John H Yim, City of Hope Medical Center

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)

October 22, 2021

Primary Completion (Estimated)

October 22, 2026

Study Completion (Estimated)

October 22, 2026

Study Registration Dates

First Submitted

February 4, 2022

First Submitted That Met QC Criteria

February 4, 2022

First Posted (Actual)

February 8, 2022

Study Record Updates

Last Update Posted (Actual)

February 23, 2026

Last Update Submitted That Met QC Criteria

February 20, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 21129 (Other Identifier: City of Hope Medical Center)
  • P30CA033572 (U.S. NIH Grant/Contract)
  • NCI-2021-12556 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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