Desiccated Thyroid Extract Combined With Levothyroxine for TSH Suppression Therapy in DTC

NCT ID: NCT07239674

Last Updated: 2025-11-20

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 646 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-11-30
• Study Completion Date: 2028-06-30

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.

Detailed Description

This study is a multicenter, open-label, randomized controlled trial. 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. Exclusion criteria: (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.

Stage 1 prospectively enrolls patients who underwent initial DTC surgery at participating sites, were classified as intermediate or high recurrence risk, subsequently failed to achieve target TSH suppression on L-T4 monotherapy while having FT4 ≥ 90 % of the normal upper limit. The TSH-suppressive regimen is switched to DTE + L-T4, creating a before-and-after self-control study. Stage 2 screens patients scheduled for initial DTC surgery; eligible participants are randomized 1:1 to experimental arm (DTE + L-T4 combination) and control arm (L-T4). The stage 2 target sample size is 446 patients (223 per arm).

Data collection includes: (1) Baseline characteristics: sex, age, BMI, comorbidities (cardiovascular, endocrine, thyroid, etc.), prior neck irradiation; (2) Pre-operative imaging/labs: laryngoscopy, thyroid US, TSH, FT3, FT4, TT3, TT4; (3) Operative data: procedure type, date, extent of lymph-node dissection; (4) Symptom/QoL: ThyPRO-39 questionnaire; (5) hair-pull test for alopecia; (6) Genetics: DIO2 polymorphism; (6) Post-operative plan: initial TSH-suppression dose, first dosing date, RAI administration; (7) Pathology: histology, TNM stage, molecular results, ATA risk stratum. Follow-up at 1, 3, 6, 9, 12 months post-op and 1 month after every dose adjustment: (1) Vital signs, weight, TSH-suppression details; (2) Imaging/labs: thyroid US, TSH, FT3, FT4, TT3, TT4, Tg, TgAb, calcium, 25-OH-VD; (3) Adverse events: cardiovascular, musculoskeletal, neurologic, GI, allergic reactions; (4) ThyPRO-39 and hair-pull test repeated at each visit.

Conditions

Intermediate-to-High Risk Differentiated Thyroid Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimantal Group

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

Group Type: EXPERIMENTAL

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

Intervention Type: 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.

Control group

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• (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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

West China Tianfu Hospital, Sichuan University

UNKNOWN

Sponsor Role: collaborator

Shang Jin Hospital of West China Hospital,Sichuan University

UNKNOWN

Sponsor Role: collaborator

Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, China

UNKNOWN

Sponsor Role: collaborator

First Affiliated Hospital of Guangxi Medical University

OTHER

Sponsor Role: collaborator

First Affiliated Hospital of Kunming Medical University

OTHER

Sponsor Role: collaborator

Xijing Hospital of Airforce Medical University

UNKNOWN

Sponsor Role: collaborator

Sir Run Run Shaw Hospital

OTHER

Sponsor Role: collaborator

First Affiliated Hospital of Chongqing Medical University

OTHER

Sponsor Role: collaborator

The Affiliated Hospital Of Guizhou Medical University

OTHER

Sponsor Role: collaborator

The Second Affiliated Hospital of Kunming Medical University

OTHER

Sponsor Role: collaborator

The Second Affiliated Hospital of Lanzhou University

UNKNOWN

Sponsor Role: collaborator

The Fifth People's Hospital of Qinghai Province （Qinghai Province Cancer Hospital)

UNKNOWN

Sponsor Role: collaborator

The Affiliated Hospital of Inner Mongolia Medical University

OTHER

Sponsor Role: collaborator

The First Affiliated Hospital of Shanxi Medical University

OTHER

Sponsor Role: collaborator

General Hospital of Ningxia Medical University

OTHER

Sponsor Role: collaborator

Yantai Yuhuangding Hospital

OTHER

Sponsor Role: collaborator

Sun Yat-sen University

OTHER

Sponsor Role: collaborator

Zhongnan Hospital

OTHER

Sponsor Role: collaborator

West China Hospital

OTHER

Sponsor Role: lead

Responsible Party

Yu Feng

West China Hospital, Sichuan University

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

ZhiHui Li

Role: CONTACT

rockoliver@vip.sina.com

+86 18980602027

Yu Feng

Role: CONTACT

1350502131@qq.com

+86 15183042703

References

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

Reference Type: 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.

Reference Type: RESULT

PMID: 28960722 (View on PubMed)

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.

Reference Type: RESULT

PMID: 37668013 (View on PubMed)

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.

Reference Type: RESULT

PMID: 33178770 (View on PubMed)

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.

Reference Type: RESULT

PMID: 34935859 (View on PubMed)

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.

Reference Type: RESULT

PMID: 34670546 (View on PubMed)

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.

Reference Type: RESULT

PMID: 35639050 (View on PubMed)

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.

Reference Type: RESULT

PMID: 34302730 (View on PubMed)

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 J, 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.

Reference Type: RESULT

PMID: 40844370 (View on PubMed)

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.

Reference Type: RESULT

PMID: 33662333 (View on PubMed)

Other Identifiers

2025(1862)

Identifier Type: -

Identifier Source: org_study_id