NCT07239674

Brief Summary

The global incidence of Differentiated Thyroid Cancer (DTC) is rising. While surgery followed by TSH suppression is the standard of care, achieving target TSH levels with levothyroxine (L-T4) monotherapy remains challenging, with only 25-70% of intermediate/high-risk patients attaining it within 6-8 months. This therapeutic dilemma stems from three key issues: impaired T4-to-T3 conversion due to DIO2 polymorphisms, the non-physiological hormone ratio of T4 monotherapy, and L-T4's narrow therapeutic window. This often results in an "under- versus over-suppression" paradox, increasing risks of recurrence, atrial fibrillation, and osteoporosis. Combining L-T4 with desiccated thyroid extract (DTE; T4:T3 ≈ 4:1) may overcome these limitations by bypassing DIO2 defects and providing a more physiological hormone profile, thereby potentially improving TSH control while mitigating side effects. Supported by the 2023 Chinese guidelines and our promising pilot data (82% cumulative target attainment at a median of 1.4 months), we propose a two-stage national study: a multicenter cohort study followed by a randomized trial, to generate high-level evidence for this combination therapy in high-risk DTC.

Trial Health

65
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
646

participants targeted

Target at P75+ for phase_3

Timeline
26mo left

Started Nov 2025

Typical duration for phase_3

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress15%
Nov 2025Jun 2028

First Submitted

Initial submission to the registry

November 16, 2025

Completed
4 days until next milestone

First Posted

Study publicly available on registry

November 20, 2025

Completed
10 days until next milestone

Study Start

First participant enrolled

November 30, 2025

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 30, 2027

Expected
7 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2028

Last Updated

November 20, 2025

Status Verified

November 1, 2025

Enrollment Period

2 years

First QC Date

November 16, 2025

Last Update Submit

November 16, 2025

Conditions

Intermediate-to-High Risk Differentiated Thyroid Cancer

Keywords

TSH Suppression TherapyDesiccated Thyroid ExtractDifferentiated Thyroid CancerLevothyroxine

Outcome Measures

Primary Outcomes (2)

  • Rate of adequate TSH suppression

    Rate of adequate TSH suppression defined as TSH level reaching the preset suppression target. TSH suppression targets follow the 2023 Chinese Guidelines for Thyroid Nodules and Differentiated Thyroid Cancer (2nd edition): during the initial treatment phase (within 1 year after surgery ± ¹³¹I therapy), serum TSH should be \< 0.1 mU/L for high-risk patients and 0.1-0.5 mU/L for intermediate-risk patients.

    1, 3, 6, 9, 12 months postoperative and 1 month after every dose adjustment

  • Time to TSH suppression target

    Median number of days from treatment initiation to the first measurement meeting TSH suppression criteria.

    1, 3, 6, 9, 12 months postoperative and 1 month after every dose adjustment

Secondary Outcomes (5)

  • Thyroid function test

    Preoperative, 1, 3, 6, 9, 12 months postoperative and 1 month after every dose adjustment

  • Symptoms and quality of life related to thyroid dysfunction

    Preoperative, 1, 3, 6, 9, 12 months postoperative and 1 month after every dose adjustment

  • Assessment of hair-loss severity

    Preoperative, 1, 3, 6, 9, 12 months postoperative and 1 month after every dose adjustment

  • Adverse events (AEs)

    1, 3, 6, 9, 12 months postoperative and 1 month after every dose adjustment

  • DIO2 polymorphism analysis

    Preoperative

Study Arms (2)

Experimantal Group

EXPERIMENTAL

Combination therapy with desiccated thyroid extract and levothyroxine (DTE + L-T4) as the TSH-suppressive regimen.

Drug: desiccated thyroid extract (DTE)+levothyroxine (L-T4)

Control group

NO INTERVENTION

Levothyroxine (L-T4) monotherapy as the TSH-suppressive regimen.

Interventions

desiccated thyroid extract (DTE)+levothyroxine (L-T4)DRUG

Desiccated thyroid extract (DTE) is a dry preparation obtained from animal thyroid glands that contains both thyroxine (T4) and triiodothyronine (T3) in an approximately 4:1 ratio, closely matching the physiological hormone profile secreted by the human thyroid. Combining DTE with levothyroxine (L-T4) may overcome current therapeutic bottlenecks. First, L-T4 given in adequate doses provides the major T4-mediated TSH suppression, while the small amount of T3 supplied by DTE acts directly on pituitary thyrotrophs, bypassing impaired DIO2 conversion; this pharmacodynamic synergy yields tighter TSH control, steadier serum levels, and fewer thyrotoxic side-effects. Second, because thyroid-hormone receptor isoforms are differentially expressed across tissues and display distinct T4/T3 affinities, the combination allows finer tuning of thyroid hormone signaling-maintaining adequate tumor suppression while attenuating adverse cardiac and skeletal effects.

Experimantal Group

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Stage 1 eligibility: (1) Age ≥ 18 years；(2) Histologically proven DTC after initial surgery (± ¹³¹I)；(3) ATA recurrence risk intermediate (low-intermediate or high-intermediate) or high；(4) On L-T4 monotherapy: TSH above target despite FT4 ≥ 90 % of normal upper limit；(5) Signed informed consent and agreement to follow-up. Stage 2 eligibility: (1) Age 18-70 years (inclusive)；(2) Histologically proven DTC undergoing first-time surgery；(3) ATA recurrence risk intermediate (low-intermediate or high-intermediate) or high；(4) Signed informed consent and agreement to post-operative follow-up.

You may not qualify if:

  • (1) Non-DTC histology; (2) Hyperthyroidism, toxic adenoma, or toxic nodular goiter; (3) Malabsorptive GI disorders (e.g., H.-pylori gastritis, atrophic gastritis, celiac disease) or history of gastric bypass; (4) Hypersensitivity to levothyroxine or desiccated thyroid; (5) Angina, coronary artery disease, tachyarrhythmia, osteoporosis; (6) Concurrent malignancy; (7) Pregnant, lactating, or planning pregnancy within 12 months; (8) Severe COPD, hepatic or renal insufficiency, uncontrolled hypertension or diabetes, or any condition that could bias outcome assessment; (9) Chronic use of psychotropics, systemic glucocorticoids, amiodarone, chemotherapy, iron, thionamides, PPIs, or other drugs interfering with thyroid hormone; (10) Previous exposure to levothyroxine, desiccated thyroid, or T3 preparations; (11) Participation in another clinical trial that could interfere with this study.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (10)

  • Turner, H.L., van Etten, J., Firth, D. et al. Modelling rankings in R: the PlackettLuce package. Computational Statistics.2020; 35(3): 1027-1057.

    RESULT

  • Fussey JM, Khan H, Ahsan F, Prashant R, Pettit L. Thyroid-stimulating hormone suppression therapy for differentiated thyroid cancer: The role for a combined T3/T4 approach. Head Neck. 2017 Dec;39(12):2567-2572. doi: 10.1002/hed.24926. Epub 2017 Sep 27.

    PMID: 28960722RESULT

  • Hao D, Tian L, He H, Zhu C, Guo L, Zhang K, Zhang J. Efficacy and safety of postoperative levothyroxine sodium tablets for improving serum thyroid hormone levels and tumor marker levels in patients with thyroid tumors. Eur J Transl Myol. 2023 Sep 5;33(3):11582. doi: 10.4081/ejtm.2023.11582.

    PMID: 37668013RESULT

  • Wang Z, Angell TE, Sun W, Qin Y, He L, Dong W, Zhang D, Zhang T, Shao L, Lv C, Zhang P, Guan H, Zhang H. Analysis of the strategy of LT4 prescribing and TSH monitoring for thyroid carcinoma after lobectomy. Ann Transl Med. 2020 Oct;8(19):1238. doi: 10.21037/atm-20-4890.

    PMID: 33178770RESULT

  • Chen W, Li J, Peng S, Hong S, Xu H, Lin B, Liang X, Liu Y, Liang J, Zhang Z, Ye Y, Liu F, Lin C, Xiao H, Lv W. Association of Total Thyroidectomy or Thyroid Lobectomy With the Quality of Life in Patients With Differentiated Thyroid Cancer With Low to Intermediate Risk of Recurrence. JAMA Surg. 2022 Mar 1;157(3):200-209. doi: 10.1001/jamasurg.2021.6442.

    PMID: 34935859RESULT

  • Ming J, Zhu JQ, Zhang H, Sun H, Wang J, Cheng RC, Xie L, Li XR, Tian W, Huang T. A multicenter, prospective study to observe the initial management of patients with differentiated thyroid cancer in China (DTCC study). BMC Endocr Disord. 2021 Oct 21;21(1):208. doi: 10.1186/s12902-021-00871-x.

    PMID: 34670546RESULT

  • Yavuz DG, Yazan CD, Hekimsoy Z, Aydin K, Gokkaya N, Ersoy C, Akalin A, Topaloglu O, Aydogan BI, Dilekci ENA, Alphan Uc Z, Cansu GB, Ozsari L, Iyidir OT, Olgun ME, Keskin L, Mert M, Can B, Gungor K, Galip T, Canturk Z, Elbuken G, Pekkolay Z, Kutbay NO, Yorulmaz G, Kalkan AT, Unsal YA, Yay A, Karagun B, Bozkur E. Assesment of attainment of recommended TSH levels and levothyroxine compliance in differentiated thyroid cancer patients. Clin Endocrinol (Oxf). 2022 Dec;97(6):833-840. doi: 10.1111/cen.14787. Epub 2022 Jun 12.

    PMID: 35639050RESULT

  • Ku EJ, Yoo WS, Lee EK, Ahn HY, Woo SH, Hong JH, Chung HK, Park JW. Effect of TSH Suppression Therapy on Bone Mineral Density in Differentiated Thyroid Cancer: A Systematic Review and Meta-analysis. J Clin Endocrinol Metab. 2021 Nov 19;106(12):3655-3667. doi: 10.1210/clinem/dgab539.

    PMID: 34302730RESULT

  • Ringel MD, Sosa JA, Baloch Z, Bischoff L, Bloom G, Brent GA, Brock PL, Chou R, Flavell RR, Goldner W, Grubbs EG, Haymart M, Larson SM, Leung AM, Osborne JR, Ridge JA, Robinson B, Steward DL, Tufano RP, Wirth LJ. 2025 American Thyroid Association Management Guidelines for Adult Patients with Differentiated Thyroid Cancer. Thyroid. 2025 Aug;35(8):841-985. doi: 10.1177/10507256251363120.

    PMID: 40844370RESULT

  • Miranda-Filho A, Lortet-Tieulent J, Bray F, Cao B, Franceschi S, Vaccarella S, Dal Maso L. Thyroid cancer incidence trends by histology in 25 countries: a population-based study. Lancet Diabetes Endocrinol. 2021 Apr;9(4):225-234. doi: 10.1016/S2213-8587(21)00027-9. Epub 2021 Mar 1.

    PMID: 33662333RESULT

MeSH Terms

Conditions

Thyroid Diseases

Interventions

Thyroid (USP)Thyroxine

Condition Hierarchy (Ancestors)

Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Thyroid HormonesHormonesHormones, Hormone Substitutes, and Hormone AntagonistsAmino Acids, AromaticAmino Acids, CyclicAmino AcidsAmino Acids, Peptides, and Proteins

Central Study Contacts

ZhiHui Li

CONTACT

+86 18980602027rockoliver@vip.sina.com

Yu Feng

CONTACT

+86 151830427031350502131@qq.com

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
West China Hospital, Sichuan University

Study Record Dates

First Submitted

November 16, 2025

First Posted

November 20, 2025

Study Start

November 30, 2025

Primary Completion (Estimated)

November 30, 2027

Study Completion (Estimated)

June 30, 2028

Last Updated

November 20, 2025

Record last verified: 2025-11