Toxic Nodular GoitrePhase 4NCT00150124
Block-replacement Therapy During Radioiodine Therapy
A Phase 4 study testing MTZ+LT4 and Methimazole in people with Toxic Nodular Goitre and Graves' Disease, run by Steen Bonnema at 1 site in Denmark.
Trial summary
Background: The use of radioactive iodine (131I) therapy as the definite cure of hyperthyroidism is widespread. According to a survey on the management of Graves' disease, thirty per cent of physicians prefer to render their patients euthyroid by antithyroid drugs (ATD) prior to 131I therapy. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Toxic Nodular Goitre, Graves' Disease
- What is being tested?
- MTZ+LT4 and Methimazole
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteDenmark
- Study dates
- Jan 2003to Mar 2009
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Hyperthyroid patients going to be treated with radioiodine either due to recurrent Graves' disease or toxic nodular goiter.
Who cannot join
- Age < 18 yrs.
- Allergy to anti-thyroid drugs
- Substernal or large (> 100ml) goiter
- Severe endocrine ophthalmopathy
- Pregnancy or lactation
- Suspicion of thyroid malignancy
- Unsafe contra-conception
- Physical or mental condition that hinders corporation
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Department of Endocrinology, Odense University Hospital
Odense, Funen, 5000
About this study
Official title: The Influence of Continuous Block-replacement Therapy on the Effect of Radioiodine in Patients With Hyperthyroidism
Background: The use of radioactive iodine (131I) therapy as the definite cure of hyperthyroidism is widespread. According to a survey on the management of Graves' disease, thirty per cent of physicians prefer to render their patients euthyroid by antithyroid drugs (ATD) prior to 131I therapy. This strategy is presumably chosen to avoid 131I induced 'thyroid storm', which, however, is rarely encountered. Several studies have consistently shown that patients who are treated with ATD prior to 131I therapy have an increased risk of treatment failure. Mostly, patients with Graves' disease have been studied, while other studies were addressed also toxic nodular goiter. Thus, it is generally accepted that ATD have 'radioprotective' properties, although this view is almost exclusively based on retrospective data and is still under debate. Indeed, this dogma was recently challenged by two randomized trials in Graves' disease, none of which showed such an adverse effect of methimazole pretreatment. It cannot be excluded that the earlier results may have been under influence of selection bias, a source of error almost unavoidable in retrospective studies. Whether ATD is radioprotective also when used in the post 131I period has also been debated. In the early period 131I therapy following a transient rise in the thyroid hormones is seen which may give rise to discomfort in some patients. The continuous use of ATD during 131I therapy, possibly in combination with levothyroxine (BRT: block-replacement therapy), leads to more stable levels of the thyroid hormones. By resuming ATD following 131I therapy, euthyroidism can usually be maintained until the destructive effect of 131I ensues. Nevertheless, many physicians prefer not to resume ATD, probably due to reports supporting that such a strategy reduces the cure rate. Parallel to the issue of ATD pretreatment, the evidence is based on retrospective studies and the ideal set-up should be reconsidered. To underscore the importance of performing randomized trials we showed recently that resumption of methimazole seven days after 131I therapy had no influence on the final outcome.
Aim:To clarify by a randomized trial whether BRT during radioiodine therapy of hyperthyroid patients influences the final outcome of this therapy, in a comparison with a regime in which methimazole as mono-therapy is discontinued 8 days before radioiodine.
Patients and Methods: Consecutive patients suffering from recurrent Graves' disease (n=50) or a toxic nodular goiter (n=50) are included. All patients are rendered euthyroid by methimazole (MMI) and randomized either to stop MMI eight days before 131I or to be set on BRT. This latter medication continues until three months after 131I. Calculation of the 131I activity (max. 600 MBq) includes an assessment of the 131I half-life and the thyroid volume. Patients are followed for one year with close monitoring of the thyroid function.
- Conditions
- Toxic Nodular Goitre, Graves' Disease
- Being tested
- MTZ+LT4, Methimazole
- Keywords
- Radioiodine therapy, Graves' disease, toxic nodular goiter, antithyroid drugs, levothyroxine, radioprotection
- Medical subject headings
- Graves Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MTZ+LT4Drug
MethimazoleDrug
| Study group | Role | What they receive |
|---|---|---|
| block-replacement therapy | Experimental | BRT regimen until 3 months after 131I therapy Receives: Drug: MTZ+LT4 |
| methimazole | Active comparator | methimazole stopped 8 days before 131I therapy Receives: Drug: Methimazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Thyroid function after one year of follow-up
Measured: one year
Secondary outcomes (2)
Thyroid radioiodine 131I uptake
Measured: one month
Thyroid volume after one year of follow-up
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2005 (estimated)
- Study startJan 2003
- Primary completionDec 2008
- Study completionMar 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Toxic Nodular GoitreStudies 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Steen Bonnema
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Steen Bonnema, Odense University Hospital
- Investigators
- Steen J. Bonnema, MD, PhD, Principal investigator, Odense University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00150124
- Sponsor's protocol ID
- 012
- Status last verified
- Dec 2013
- First submitted
- 6 Sep 2005
- Last updated
- 4 Dec 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Bonnema SJ, Grupe P, Boel-Jorgensen H, Brix TH, Hegedus L. A randomized trial evaluating a block-replacement regimen during radioiodine therapy. Eur J Clin Invest. 2011 Jul;41(7):693-702. doi: 10.1111/j.1365-2362.2010.02452.x. Epub 2010 Dec 22.
PubMed 21175612
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Influence of Continuous Block-replacement Therapy on the Effect of Radioiodine in Patients With Hyperthyroidism
- ClinicalTrials.gov ID
- NCT00150124
- Acronym / sponsor ID
- 012
- Conditions
- Toxic Nodular Goitre, Graves' Disease
- Keywords
- Radioiodine therapy, Graves' disease, toxic nodular goiter, antithyroid drugs, levothyroxine, radioprotection
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Steen BonnemaUniversity, hospital or other
- Study start
- Jan 2003
- Primary completion
- Dec 2008 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 8 Sep 2005 (estimated)
- 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.
Background: The use of radioactive iodine (131I) therapy as the definite cure of hyperthyroidism is widespread. According to a survey on the management of Graves' disease, thirty per cent of physicians prefer to render their patients euthyroid by antithyroid drugs (ATD) prior to 131I therapy. This strategy is presumably chosen to avoid 131I induced 'thyroid storm', which, however, is rarely encountered. Several studies have consistently shown that patients who are treated with ATD prior to 131I therapy have an increased risk of treatment failure. Mostly, patients with Graves' disease have been studied, while other studies were addressed also toxic nodular goiter. Thus, it is generally accepted that ATD have 'radioprotective' properties, although this view is almost exclusively based on retrospective data and is still under debate. Indeed, this dogma was recently challenged by two randomized trials in Graves' disease, none of which showed such an adverse effect of methimazole pretreatment. It cannot be excluded that the earlier results may have been under influence of selection bias, a source of error almost unavoidable in retrospective studies. Whether ATD is radioprotective also when used in the post 131I period has also been debated. In the early period 131I therapy following a transient rise in the thyroid hormones is seen which may give rise to discomfort in some patients. The continuous use of ATD during 131I therapy, possibly in combination with levothyroxine (BRT: block-replacement therapy), leads to more stable levels of the thyroid hormones. By resuming ATD following 131I therapy, euthyroidism can usually be maintained until the destructive effect of 131I ensues. Nevertheless, many physicians prefer not to resume ATD, probably due to reports supporting that such a strategy reduces the cure rate. Parallel to the issue of ATD pretreatment, the evidence is based on retrospective studies and the ideal set-up should be reconsidered. To underscore the importance of performing randomized trials we showed recently that resumption of methimazole seven days after 131I therapy had no influence on the final outcome.
Aim:To clarify by a randomized trial whether BRT during radioiodine therapy of hyperthyroid patients influences the final outcome of this therapy, in a comparison with a regime in which methimazole as mono-therapy is discontinued 8 days before radioiodine.
Patients and Methods: Consecutive patients suffering from recurrent Graves' disease (n=50) or a toxic nodular goiter (n=50) are included. All patients are rendered euthyroid by methimazole (MMI) and randomized either to stop MMI eight days before 131I or to be set on BRT. This latter medication continues until three months after 131I. Calculation of the 131I activity (max. 600 MBq) includes an assessment of the 131I half-life and the thyroid volume. Patients are followed for one year with close monitoring of the thyroid function.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| block-replacement therapy | Experimental | Drug: MTZ+LT4BRT regimen until 3 months after 131I therapy |
| methimazole | Active comparator | Drug: Methimazolemethimazole stopped 8 days before 131I therapy |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Hyperthyroid patients going to be treated with radioiodine either due to recurrent Graves' disease or toxic nodular goiter.
Key exclusion criteria (8 listed)
- Age < 18 yrs.
- Allergy to anti-thyroid drugs
- Substernal or large (> 100ml) goiter
- Severe endocrine ophthalmopathy
- Pregnancy or lactation
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 |
|---|---|---|
| MTZ+LT4 | Drug | block-replacement therapy |
| Methimazole | Drug | methimazole |
Primary outcome
Thyroid function after one year of follow-up
Time frame: one year
2 secondary outcomes
Thyroid radioiodine 131I uptake
Time frame: one month
Thyroid volume after one year of follow-up
Time frame: one year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2013.
- Derived from this study: PubMed 21175612Bonnema SJ, Grupe P, Boel-Jorgensen H, Brix TH, Hegedus L. A randomized trial evaluating a block-replacement regimen during radioiodine therapy. Eur J Clin Invest. 2011 Jul;41(7):693-702. doi: 10.1111/j.1365-2362.2010.02452.x. Epub 2010 Dec 22.
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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. This study is not recruiting at the moment.
Steen J. Bonnema, MD, PhD principal investigator
Odense University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing MTZ+LT4 and Methimazole in people with Toxic Nodular Goitre and Graves' Disease, run by Steen Bonnema at 1 site in Denmark.
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 1 inclusion and 8 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: finished, as of the sponsor's last update on 4 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Thyroid function after one year of follow-up (time frame: one year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00150124, which also lists 1 linked publication.
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 4 Dec 2013.