A Phase 3 interventional study of desiccated thyroid extract (DTE)+levothyroxine (L-T4) in Intermediate-to-High Risk Differentiated Thyroid Cancer, sponsored by West China Hospital. Not yet recruiting. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2025-11-20.
Sponsored by West China Hospital · Phase 3, Interventional, and Treatment
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.
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.
Exclusion Criteria:
Combination therapy with desiccated thyroid extract and levothyroxine (DTE + L-T4) as the TSH-suppressive regimen.
Drug: desiccated thyroid extract (DTE)+levothyroxine (L-T4)
Levothyroxine (L-T4) monotherapy as the TSH-suppressive regimen.
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.
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.
Time frame: 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.
Time frame: 1, 3, 6, 9, 12 months postoperative and 1 month after every dose adjustment
Thyroid function test
Thyroid function parameters (TSH, FT3, FT4, TT3, TT4) are measured at every follow-up visit to evaluate the physiological stability of hormone replacement.
Time frame: Preoperative, 1, 3, 6, 9, 12 months postoperative and 1 month after every dose adjustment
Symptoms and quality of life related to thyroid dysfunction
THyPRO-39
Time frame: Preoperative, 1, 3, 6, 9, 12 months postoperative and 1 month after every dose adjustment
Assessment of hair-loss severity
Hair-pull test.
Time frame: Preoperative, 1, 3, 6, 9, 12 months postoperative and 1 month after every dose adjustment
Adverse events (AEs)
Adverse events (AEs) refer to any unfavorable medical occurrences that develop during the clinical trial, regardless of whether they are related to the investigational medication. They include: Thyroid-hormone-excess-related AEs * Cardiovascular system: tachycardia, angina, cardiac insufficiency, atrial fibrillation and other arrhythmias. * Musculoskeletal system: osteoporosis, fractures, bone pain. Hypersensitivity/allergic reactions
Time frame: 1, 3, 6, 9, 12 months postoperative and 1 month after every dose adjustment
DIO2 polymorphism analysis
Genomic DNA is extracted from pre-operative blood. The region containing the target SNP is amplified by PCR, digested with a restriction endonuclease, and genotypes are assigned after electrophoresis based on fragment sizes. The data will be used to explore the relationship between DIO2 genotype, TSH-suppression efficacy, and the FT3/FT4 ratio, providing a molecular basis for individualized therapy.
Time frame: Preoperative
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Plan to share: Undecided
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West China Hospital