Differentiated Thyroid CancerTHRIVENCT06647602
Thyroid Hormone Replacement After Radio Iodine: Value and Efficacy
An observational study of Differentiated Thyroid Cancer and Thyroid Cancer, run by University Medical Center Groningen at 2 sites in Netherlands.
Trial summary
This study will be a multicentre prospective cohort study on TH-substitution after thyroid hormone withdrawal preceding radioiodine treatment. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Differentiated Thyroid Cancer, Thyroid Cancer, Levothyroxine
- What is being tested?
- Euthyrox (levothyroxine) and Cytomel (liothyronine)
- Type of treatment
- Pill or oral medicine
- How many people
- 40 participants
- Where
- 2 sitesNetherlands
- Study dates
- 1 Sep 2026to 31 Dec 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: This study will include patients with a histologically confirmed high-risk DTC, men and women aged 18-75 years. Patients have to be prepared to RAI with TH-withdrawal and treated according to the ATA guidelines.
Who may be able to join
- Histologically confirmed DTC (papillary thyroid carcinoma, follicular thyroid carcinoma, oncocytic thyroid carcinoma)
- Classified as high-risk DTC according to the ATA guidelines or, patients for whom the risk of a recurrence is estimated to be higher based on clinical features (assessed by their treating physician).
- Prepared for RAI-therapy with TH-withdrawal
- Patients must be fit to adhere to the study protocol
- Patients must be able to read and understand the Dutch language
Who cannot join
- Pregnancy
- Patients with comorbidities, such as severe heart failure, (poorly controlled) atrial fibrillation, of which the treating physician decides that L-T3 is unsuitable.
- Conditions or drugs interfering with thyroid hormone uptake:
- Patients with a history of atrophic gastritis
- Patients using proton-pomp inhibitors
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands2 sites
University Medical Center Groningen (UMCG)
Groningen, Provincie Groningen, 9700RB
Mirthe Links, Bsc, +31 50 3610973, m.h.links@umcg.nl
Radboud University Nijmegen
Nijmegen
Mirthe Links, Bsc, +31 50 3610973, m.h.links@umcg.nl
About this study
This study will be a multicentre prospective cohort study on TH-substitution after thyroid hormone withdrawal preceding radioiodine treatment.
Read the detailed description
While treatment with L-T4 after TH-withdrawal is widely used in DTC patients to suppress TSH and improve hypothyroid symptoms, the value of L-T3 addition in initiation of TH treatment has not been evaluated in this context. Lifelong monotherapy with L-T3 should not be preferred over L-T4 yet, short-term use of L-T3 to initiate TH-supplementation can be safely implemented. We hypothesize that initial treatment with L-T4+L-T3 combination treatment can have a more direct effect on TSH-levels and earlier relieve of hypothyroid symptoms resulting in a better QoL. We will conduct a prospective cohort study comparing the initiation of TH-supplementation after TH-withdrawal in two cohorts of DTC patients: patients receiving L-T4+LT3 with a gradually decrease of L-T3 dose in time, and patients receiving L-T4 only. We will compare potency to suppress TSH, effect on QoL and effects on thyroid- and cardiovascular parameters. Patients (18-75 years) diagnosed with high-risk DTC after TH-withdrawal will be eligible for inclusion. The primary objective is to compare the proportion of patients reaching target TSH-levels after two weeks of substitution with L-T3 or L-T4.
Secondary objectives are to compare the effects of L-T4+L-T3 or L-T4 in the first 3 months of treatment on serum thyroid parameters TSH and Tg, quality of life, and cardiovascular parameters
- Conditions
- Differentiated Thyroid Cancer, Thyroid Cancer, Levothyroxine, Liothyronine, Thyroid Hormones
- Being tested
- Euthyrox (levothyroxine), Cytomel (liothyronine)
- Medical subject headings
- Thyroid Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Euthyrox (levothyroxine)Drug
Euthyrox (levothyroxine sodium tablets; L-T4) is a thyromimetic synthetic drug identical to T4. Patients will recieve levothyroxine (euthyrox) in a dose of 2 μg × kg body weight / day.
Cytomel (liothyronine)Drug
Cytomel (liothyronine sodium tablets; L-T3) is a thyromimetic synthetic drug identical to T3.
The patients in this cohort recieve L-T4+L-T3 combination therapy. The L-T4 dose will be 2 μg × kg body weight / day, equal to the dose in the other interventional arm. L-T3 will be added twice daily from the first day of combination treatment, in dosages gradually decreasing from 25 ug 2/day to 5 ug 2/day over a time span of 3 weeks after which L-T3 is stopped.
| Study group | Role | What they receive |
|---|---|---|
| TH-combination cohort | L-T4+L-T3 combination according to local protocol. Receives: Drug: Cytomel (liothyronine) | |
| Levothyroxine cohort | L-T4 monotherapy according to local protocol. Receives: Drug: Euthyrox (levothyroxine) |
What is being measured
The primary outcome is the main question the study is designed to answer.
TSH after two weeks of TH substitution
The percentage of patients reaching target TSH (<0.5 mU/L) after two weeks of L-T3+L-T4 substitution compared to patients with L-T4-substitution.
Measured: Before and after 2 weeks of TH-substitution
Secondary outcomes (5)
TSH (mU/L)
The % of decrease of serum thyroid parameters TSH after 1, 2, 4, 6, and 12 weeks of TH-substitution.
Measured: Before and after 1, 2, 4, 6, and 12 weeks of TH-substitution.
Thyroglobulin (Tg; ng/mL)
The % of decrease of serum thyroid parameters Tg after 1, 2, 4, 6, and 12 weeks of TH-substitution.
Tg is a precursor of T3 and T4 and is a measurement for remaining thyroid (cancer) cells. Tg-levels are affected by TSH and therefore, we expect by reducing TSH-levels to also reduce Tg levels. Consecutive Tg-measurements in this study act as a secondary measure for TH substitution. Since Tg-values between patients variable, we will use the % decrease instead of absolute values.
Measured: Before and after 1, 2, 4, 6, and 12 weeks of TH-substitution
QoL in patients treated with L-T3 or L-T4
Quality of life will be assessed using standardized QoL questionnaires for thyroid- and thyroid cancer patient reported outcome. Our aim is to compare improvement of hypothyroid symptoms after initiation of therapy, and evaluate whether sings of hyperthyroidism and possible overtreatment are present. We will use the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 (core measure QoL questionnaire) in combination with the THYCA-QoL (additional thyroid cancer-specific part).
Measured: Before and after 2, 6, and 12 weeks of TH-substitution
Heart rate (HR; bpm)
Cardiovascular parameters will be assessed during visits to the outpatient clinic before initiation of TH-substitution (during hypothyroidism) and after 6 weeks of TH-treatment. Patients will be compared intra- and interindividually.
Measured: Before and after 6 and 12 weeks of TH-substitution
Blood pressure (BP; mmHg)
Cardiovascular parameters will be assessed during visits to the outpatient clinic before initiation of TH-substitution (during hypothyroidism) and after 6 and 12 weeks of TH-treatment. Patients will be compared intra- and interindividually.
Measured: Before and after 6 and 12 weeks of TH-substitution
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2024
- Study start1 Sep 2026 (estimated)
- Primary completion31 Mar 2028 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Differentiated Thyroid CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Collaborators
- Radboud University Medical Center
- Responsible party
- Sponsor
- Investigators
- Wouter Zandee, MD/PhD, Principal investigator, University Medical Center Groningen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06647602
- Sponsor's protocol ID
- 11432
- Other IDs
- 2024-511668-10-00
- Acronym
- THRIVE
- Status last verified
- Feb 2026
- First submitted
- 11 Jun 2024
- Last updated
- 10 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Handling of personal data complies with the General Data Protection Regulation (GDPR; in Dutch: De uitvoeringswet algemene verorderning gegevensbescherming \[UAVG\]). Encoded data will be kept for 15 years after closure of the study and can only be used for ancillary studies after strict approval of the study protocol by the project leader (dr. W. Zandee).
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Thyroid Hormone Replacement After Radio Iodine: Value and Efficacy
- ClinicalTrials.gov ID
- NCT06647602
- Acronym / sponsor ID
- THRIVE / 11432
- Conditions
- Differentiated Thyroid Cancer, Thyroid Cancer, Levothyroxine, Liothyronine, Thyroid Hormones
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- University Medical Center GroningenUniversity, hospital or other
- Collaborators
- Radboud University Medical Center
- Study start
- 1 Sep 2026 (estimated)
- Primary completion
- 31 Mar 2028 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 18 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will be a multicentre prospective cohort study on TH-substitution after thyroid hormone withdrawal preceding radioiodine treatment.
Detailed description
While treatment with L-T4 after TH-withdrawal is widely used in DTC patients to suppress TSH and improve hypothyroid symptoms, the value of L-T3 addition in initiation of TH treatment has not been evaluated in this context. Lifelong monotherapy with L-T3 should not be preferred over L-T4 yet, short-term use of L-T3 to initiate TH-supplementation can be safely implemented. We hypothesize that initial treatment with L-T4+L-T3 combination treatment can have a more direct effect on TSH-levels and earlier relieve of hypothyroid symptoms resulting in a better QoL. We will conduct a prospective cohort study comparing the initiation of TH-supplementation after TH-withdrawal in two cohorts of DTC patients: patients receiving L-T4+LT3 with a gradually decrease of L-T3 dose in time, and patients receiving L-T4 only. We will compare potency to suppress TSH, effect on QoL and effects on thyroid- and cardiovascular parameters. Patients (18-75 years) diagnosed with high-risk DTC after TH-withdrawal will be eligible for inclusion. The primary objective is to compare the proportion of patients reaching target TSH-levels after two weeks of substitution with L-T3 or L-T4.
Secondary objectives are to compare the effects of L-T4+L-T3 or L-T4 in the first 3 months of treatment on serum thyroid parameters TSH and Tg, quality of life, and cardiovascular parameters
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TH-combination cohort | – | Drug: Cytomel (liothyronine)L-T4+L-T3 combination according to local protocol. |
| Levothyroxine cohort | – | Drug: Euthyrox (levothyroxine)L-T4 monotherapy according to local protocol. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- This study will include patients with a histologically confirmed high-risk DTC, men and women aged 18-75 years. Patients have to be prepared to RAI with TH-withdrawal and treated according to the ATA guidelines.
Key inclusion criteria (5 listed)
- Histologically confirmed DTC (papillary thyroid carcinoma, follicular thyroid carcinoma, oncocytic thyroid carcinoma)
- Classified as high-risk DTC according to the ATA guidelines or, patients for whom the risk of a recurrence is estimated to be higher based on clinical features (assessed by their treating physician).
- Prepared for RAI-therapy with TH-withdrawal
- Patients must be fit to adhere to the study protocol
- Patients must be able to read and understand the Dutch language
Key exclusion criteria (5 listed)
- Pregnancy
- Patients with comorbidities, such as severe heart failure, (poorly controlled) atrial fibrillation, of which the treating physician decides that L-T3 is unsuitable.
- Conditions or drugs interfering with thyroid hormone uptake:
- Patients with a history of atrophic gastritis
- Patients using proton-pomp inhibitors
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Euthyrox (levothyroxine)Euthyrox (levothyroxine sodium tablets; L-T4) is a thyromimetic synthetic drug identical to T4. Patients will recieve levothyroxine (euthyrox) in a dose of 2 μg × kg body weight / day. | Drug | Levothyroxine cohort |
| Cytomel (liothyronine)Cytomel (liothyronine sodium tablets; L-T3) is a thyromimetic synthetic drug identical to T3. The patients in this cohort recieve L-T4+L-T3 combination therapy. The L-T4 dose will be 2 μg × kg body weight / day, equal to the dose in the other interventional arm. L-T3 will be added twice daily from the first day of combination treatment, in dosages gradually decreasing from 25 ug 2/day to 5 ug 2/day over a time span of 3 weeks after which L-T3 is stopped. | Drug | TH-combination cohort |
Primary outcome
TSH after two weeks of TH substitution
Time frame: Before and after 2 weeks of TH-substitution
The percentage of patients reaching target TSH (<0.5 mU/L) after two weeks of L-T3+L-T4 substitution compared to patients with L-T4-substitution.
5 secondary outcomes
TSH (mU/L)
Time frame: Before and after 1, 2, 4, 6, and 12 weeks of TH-substitution.
Thyroglobulin (Tg; ng/mL)
Time frame: Before and after 1, 2, 4, 6, and 12 weeks of TH-substitution
QoL in patients treated with L-T3 or L-T4
Time frame: Before and after 2, 6, and 12 weeks of TH-substitution
Heart rate (HR; bpm)
Time frame: Before and after 6 and 12 weeks of TH-substitution
Blood pressure (BP; mmHg)
Time frame: Before and after 6 and 12 weeks of TH-substitution
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2026.
- Individual participant dataSharing planned: No. Handling of personal data complies with the General Data Protection Regulation (GDPR; in Dutch: De uitvoeringswet algemene verorderning gegevensbescherming [UAVG]). Encoded data will be kept for 15 years after closure of the study and can only be used for ancillary studies after strict approval of the study protocol by the project leader (dr. W. Zandee).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Wouter Zandee, MD/PhD principal investigator
University Medical Center Groningen
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Differentiated Thyroid Cancer and Thyroid Cancer, run by University Medical Center Groningen at 2 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 10 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mirthe Links, BSc (+31 50 3610973, m.h.links@umcg.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
TSH after two weeks of TH substitution (time frame: Before and after 2 weeks of TH-substitution). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2026.