Multinodular GoiterPhase 2NCT00454220
Study to Determine the Dose, the Safety and Effectiveness of a New Drug, Modified Release rhTSH, in Patients With Multinodular Goiter
A Phase 2 study testing MRrhTSH in people with Multinodular Goiter, run by Genzyme, a Sanofi Company at 11 sites in 8 countries.
Trial summary
The purpose of this study is to determine the safety and effectiveness of 2 different doses of modified-release recombinant human thyroid stimulating hormone (MRrhTSH) when administered with radioiodine in patients with multinodular goiter, a condition that involves the enlargement of the thyroid gland. Read more about this study
- Who is it for?
- Ages 35 to 80 years
- Conditions the study is for
- Multinodular Goiter
- What is being tested?
- MRrhTSH
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 96 participants
- Where
- 11 sitesin 8 countries
- Study dates
- Jul 2007to Jul 2011
- Phase
- Phase 2
- 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 35 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Clinical diagnosis of multinodular goiter, judged clinically and by ultrasound at Screening to be at least 40 mL, but less than or equal to 140 mL in size.
- Clinically free of thyroid cancer as determined by Fine Needle Aspiration (FNA) of all dominant and/or highly suspicious cold nodules in the goiter and cytology reports as negative for thyroid cancer. (Note: Results of FNA and cytology reports that were performed within 18 months prior to commencing Screening procedures and meet these criteria are acceptable for inclusion).
- Principal Investigator must believe that there is a minimal risk of coexistent thyroid cancer.
- Principal Investigator feels that the patient's iodine intake and/or levels will not significantly impact the results of the study (urinary iodine assay at Screening and low-iodine diet are optional and associated data will not be collected for study purposes).
- Baseline serum level of free thyroxine index (FTI) within the normal range, as determined by central lab.
- Baseline serum level of thyroid stimulating hormone (TSH) ranges from undetectable to the upper limit of the normal range, as determined by central lab.
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- Females of child-bearing potential must be on a stable hormonal contraceptive regimen (i.e., > 6 months continuous use) and/or use a double barrier method (i.e., condom and foam) through Visit 8 (i.e. the end of the Core Study).
- Through Visit 8 (6 months) of a male patient's participation in the study, it is recommended that his sexual partner(s), who are females of child-bearing potential, use the above described methods of contraception.
- Negative pregnancy tests for all women of child-bearing potential prior to participating in the study. Women aged 50 years and above and considered postmenopausal (defined as > 2 years since last menstrual period) will not need to have a pregnancy test.
- Routine blood laboratory values within normal range at Screening, as determined by central lab. Abnormal values considered to be not clinically significant by the Principal Investigator are acceptable for inclusion.
- Electrocardiogram (ECG) (12 lead, 2 minute rhythm strip) within normal limits at Screening as determined by a designated study cardiologist or appropriately qualified physician at each site. Evidence of an old myocardial infarction (MI) will exclude the patient. Patients who have ECG findings of occasional premature atrial beats, abnormal PR intervals not associated with supra ventricular tachycardia (SVT) or heart block, right bundle branch block, and heart rates ≤ 100 beats per minute (BPM) and ≥ 50 BPM may be included in this study.
- Committed to follow all protocol-required study procedures as evidenced by providing written informed consent within 21 days prior to Screening Period 2.
Who cannot join
- History of thyroid cancer.
- Previous partial or near total thyroidectomy.
- Clinical history, signs or symptoms that make thyroid cancer a higher than usual probability, such as positive immediate family history of thyroid cancer, history of head or neck irradiation, a stone-hard nodule or suspicious growth of a nodule in recent months, palpable cervical lymph nodes or nodes that on ultrasound have features suspicious for metastases (unless ruled out by biopsy or FNA).
- During the 45 days before administration of MRrhTSH or placebo (i.e., Screening Periods 1 and 2), use of propylthiouracil, methimazole or thyroxine, vitamins or supplements containing kelp or iodine (taking a multivitamin that does not contain iodine or kelp is acceptable), medications that significantly affect iodine handling such as high dose corticosteroids, high dose diuretics, or lithium (low or moderate dose diuretic use is acceptable).
- Patient has currently or within the past 60 days used retinoic acid.
- Serum calcitonin above the upper limit of normal at Screening, as determined by central lab.
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- Use of amiodarone within the prior 2 years.
- Received iodine-containing contrast agent within the past 3 months.
- Inability to complete all required visits.
- Patients with conditions in which use of beta-blockers are medically contraindicated, such as recently active asthma or clinically significant chronic obstructive pulmonary disease.
- Currently or within the past 5 years have a history of malignancy, other than squamous or basal cell carcinoma of the skin or carcinoma in situ of the cervix.
- Prior MI, even if remote; stroke within 6 months; atrial fibrillation or clinically significant arrhythmia within 6 months (patient may have mild hypertension or chronic cardiac illnesses that are well controlled on a medication regimen: blood pressure (BP) less than 140/90 mmHg after resting 5 minutes).
- A concurrent major medical disorder (e.g., documented significant cardiac disease, debilitating cardiopulmonary disease, advanced renal failure, advanced liver disease, advanced pulmonary disease, or advanced cerebral vascular disorder) that may have an impact on the capability of the patient to adequately comply with the requirements of this study.
- Women who are pregnant or lactating.
- A recent history of alcoholism, drug abuse or other disorder that might affect compliance with the protocol.
- Received investigational study medication within 30 days prior to signing informed consent and/or intends to participate in another clinical study involving the use of an investigational drug over the course of study participation.
- Patients on anticoagulants except for aspirin.
- Patients known at the time of Screening due to past testing to be human immunodeficiency virus (HIV) antibody positive or hepatitis B antigen positive (no screening for HIV or hepatitis B should be done in the study).
- Hyperthyroid symptom scale (HSS) ≥ 20.
- Patients who have received 131I in the past, and have had a lifetime exposure believed to be >10 mCi (0.37GBq) of 131I.
- History of allergy to Thyrogen.
- Sodium carboxymethylcellulose (NaCMC) allergy (including prior history of anaphylaxis following topical lidocaine, barium sulfate ingestion, or intra-articular or parenteral corticosteroid).
- Smallest cross-sectional area of the trachea (SCAT) discovered on CT to be < 60 mm2
Trial locations and contacts
11 sites in 8 countries.
11 sites in 8 countries
About this study
Official title: Study to Evaluate the Dose, Safety and Effectiveness of Modified-Release Recombinant Human Thyroid Stimulating Hormone (MRrhTSH) When Used in Conjunction With Radioiodine for the Treatment of Multinodular Goiter.
The purpose of this study is to determine the safety and effectiveness of 2 different doses of modified-release recombinant human thyroid stimulating hormone (MRrhTSH) when administered with radioiodine in patients with multinodular goiter, a condition that involves the enlargement of the thyroid gland. We will also evaluate the safety and effectiveness of radioiodine therapy alone in these patients. The goal of the treatment is to determine if there was a reduction in the size of the goiter and to study if goiter symptoms have improved after 6 months and after 36 months.
- Conditions
- Multinodular Goiter
- Being tested
- Placebo, MRrhTSH
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboOther
33 patients to placebo + 131-I arm
MRrhTSHDrug
33 patients to 0.01 mg MRrhTSH + 131-I arm
MRrhTSHDrug
33 patients to 0.03 mg MRrhTSH + 131-I arm
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Not described Receives: Other: Placebo |
| 0.01 mg MRrhTSH + 131-I arm | Experimental | Not described Receives: Drug: MRrhTSH |
| 0.03 mg MRrhTSH + 131-I arm | Experimental | Not described Receives: Drug: MRrhTSH |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline to 6 months in goiter size by computer tomography (CT) scan.
Measured: Duration of core study
Extension Phase: Change in goiter size by CT scan at 36 months versus baseline, Months 6, 12 and 24
Measured: Duration of extension phase
Secondary outcomes (10)
Change in goiter size from baseline to 6 months in smallest cross sectional area of the trachea (SCAT).
Measured: Duration of core study
The percentage of patients in each group who attained a goiter volume shrinkage at 6 months of 28% or greater.
Measured: Core Study
Extension Phase: Change in goiter size from baseline to 6, 12, 24 and 36 months by SCAT and neck ultrasound.
Measured: Duration of extension phase
Thyroid Quality of Life Questionnaire
Measured: Core Study and Extension Phase
Thyroid Stimulating Hormone (TSH), free thyroxine (FT4), total thyroxine (TT4), FT1, free triiodothyronine (FT3), total T3 (TT3).
Measured: Core Study and Extension Phase
Physical Exams, Vitals, Adverse Events, Respiratory symptoms
Measured: Core Study and Extension Phase
Routine labs, serial thyroid function tests, antibodies to MRrhTSH, antibodies against the thyroid stimulating hormone receptor, and physical exam.
Measured: Core study and extension phase
Tracheal diameter measurements determined by ultrasound at Visit 3 compared to baseline measurement.
Measured: core study - Visit 3
Electrocardiogram (ECG)
Measured: Duration of core study
Treatment-emergent hyperthyroidism (Hyperthyroid Symptom Scale (HSS) score ≥ 20).
Measured: Core study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2007 (estimated)
- Study startJul 2007
- Primary completionJul 2011
- Study completionJul 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Multinodular GoiterStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 96 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genzyme, a Sanofi Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Genzyme, a Sanofi Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00454220
- Sponsor's protocol ID
- MRTSH01505
- Status last verified
- Jun 2022
- First submitted
- 28 Mar 2007
- Last updated
- 7 Jun 2022
- Results posted
- No
- Data monitoring committee
- No
Publications
Fast S, Hegedus L, Pacini F, Pinchera A, Leung AM, Vaisman M, Reiners C, Wemeau JL, Huysmans DA, Harper W, Rachinsky I, de Souza HN, Castagna MG, Antonangeli L, Braverman LE, Corbo R, Duren C, Proust-Lemoine E, Marriott C, Driedger A, Grupe P, Watt T, Magner J, Purvis A, Graf H. Long-term efficacy of modified-release recombinant human thyrotropin augmented radioiodine therapy for benign multinodular goiter: results from a multicenter, international, randomized, placebo-controlled, dose-selection study. Thyroid. 2014 Apr;24(4):727-35. doi: 10.1089/thy.2013.0370. Epub 2014 Mar 4.
PubMed 24341527Huo Y, Xie J, Chen S, Wang H, Ma C. Recombinant human thyrotropin (rhTSH)-aided radioiodine treatment for non-toxic multinodular goitre. Cochrane Database Syst Rev. 2021 Dec 28;12(12):CD010622. doi: 10.1002/14651858.CD010622.pub2.
PubMed 34961921
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study to Evaluate the Dose, Safety and Effectiveness of Modified-Release Recombinant Human Thyroid Stimulating Hormone (MRrhTSH) When Used in Conjunction With Radioiodine for the Treatment of Multinodular Goiter.
- ClinicalTrials.gov ID
- NCT00454220
- Acronym / sponsor ID
- MRTSH01505
- Conditions
- Multinodular Goiter
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 96 participants (actual)
- Lead sponsor
- Genzyme, a Sanofi CompanyIndustry (pharma, biotech, devices)
- Study start
- Jul 2007
- Primary completion
- Jul 2011 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 30 Mar 2007 (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.
The purpose of this study is to determine the safety and effectiveness of 2 different doses of modified-release recombinant human thyroid stimulating hormone (MRrhTSH) when administered with radioiodine in patients with multinodular goiter, a condition that involves the enlargement of the thyroid gland. We will also evaluate the safety and effectiveness of radioiodine therapy alone in these patients. The goal of the treatment is to determine if there was a reduction in the size of the goiter and to study if goiter symptoms have improved after 6 months and after 36 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Other: Placebo |
| 0.01 mg MRrhTSH + 131-I arm | Experimental | Drug: MRrhTSH |
| 0.03 mg MRrhTSH + 131-I arm | Experimental | Drug: MRrhTSH |
Who may qualify
- Ages
- 35 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Clinical diagnosis of multinodular goiter, judged clinically and by ultrasound at Screening to be at least 40 mL, but less than or equal to 140 mL in size.
- Clinically free of thyroid cancer as determined by Fine Needle Aspiration (FNA) of all dominant and/or highly suspicious cold nodules in the goiter and cytology reports as negative for thyroid cancer. (Note: Results of FNA and cytology reports that were performed within 18 months prior to commencing Screening procedures and meet these criteria are acceptable for inclusion).
- Principal Investigator must believe that there is a minimal risk of coexistent thyroid cancer.
- Principal Investigator feels that the patient's iodine intake and/or levels will not significantly impact the results of the study (urinary iodine assay at Screening and low-iodine diet are optional and associated data will not be collected for study purposes).
- Baseline serum level of free thyroxine index (FTI) within the normal range, as determined by central lab.
Key exclusion criteria (23 listed)
- History of thyroid cancer.
- Previous partial or near total thyroidectomy.
- Clinical history, signs or symptoms that make thyroid cancer a higher than usual probability, such as positive immediate family history of thyroid cancer, history of head or neck irradiation, a stone-hard nodule or suspicious growth of a nodule in recent months, palpable cervical lymph nodes or nodes that on ultrasound have features suspicious for metastases (unless ruled out by biopsy or FNA).
- During the 45 days before administration of MRrhTSH or placebo (i.e., Screening Periods 1 and 2), use of propylthiouracil, methimazole or thyroxine, vitamins or supplements containing kelp or iodine (taking a multivitamin that does not contain iodine or kelp is acceptable), medications that significantly affect iodine handling such as high dose corticosteroids, high dose diuretics, or lithium (low or moderate dose diuretic use is acceptable).
- Patient has currently or within the past 60 days used retinoic acid.
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 |
|---|---|---|
| Placebo33 patients to placebo + 131-I arm | Other | Placebo |
| MRrhTSH33 patients to 0.01 mg MRrhTSH + 131-I arm | Drug | 0.01 mg MRrhTSH + 131-I arm |
| MRrhTSH33 patients to 0.03 mg MRrhTSH + 131-I arm | Drug | 0.03 mg MRrhTSH + 131-I arm |
Primary outcome
Change from baseline to 6 months in goiter size by computer tomography (CT) scan.
Time frame: Duration of core study
Extension Phase: Change in goiter size by CT scan at 36 months versus baseline, Months 6, 12 and 24
Time frame: Duration of extension phase
10 secondary outcomes
Change in goiter size from baseline to 6 months in smallest cross sectional area of the trachea (SCAT).
Time frame: Duration of core study
The percentage of patients in each group who attained a goiter volume shrinkage at 6 months of 28% or greater.
Time frame: Core Study
Extension Phase: Change in goiter size from baseline to 6, 12, 24 and 36 months by SCAT and neck ultrasound.
Time frame: Duration of extension phase
Thyroid Quality of Life Questionnaire
Time frame: Core Study and Extension Phase
Thyroid Stimulating Hormone (TSH), free thyroxine (FT4), total thyroxine (TT4), FT1, free triiodothyronine (FT3), total T3 (TT3).
Time frame: Core Study and Extension Phase
Physical Exams, Vitals, Adverse Events, Respiratory symptoms
Time frame: Core Study and Extension Phase
Routine labs, serial thyroid function tests, antibodies to MRrhTSH, antibodies against the thyroid stimulating hormone receptor, and physical exam.
Time frame: Core study and extension phase
Tracheal diameter measurements determined by ultrasound at Visit 3 compared to baseline measurement.
Time frame: core study - Visit 3
Electrocardiogram (ECG)
Time frame: Duration of core study
Treatment-emergent hyperthyroidism (Hyperthyroid Symptom Scale (HSS) score ≥ 20).
Time frame: Core study
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 7 Jun 2022.
- Results publication: PubMed 24341527Fast S, Hegedus L, Pacini F, Pinchera A, Leung AM, Vaisman M, Reiners C, Wemeau JL, Huysmans DA, Harper W, Rachinsky I, de Souza HN, Castagna MG, Antonangeli L, Braverman LE, Corbo R, Duren C, Proust-Lemoine E, Marriott C, Driedger A, Grupe P, Watt T, Magner J, Purvis A, Graf H. Long-term efficacy of modified-release recombinant human thyrotropin augmented radioiodine therapy for benign multinodular goiter: results from a multicenter, international, randomized, placebo-controlled, dose-selection study. Thyroid. 2014 Apr;24(4):727-35. doi: 10.1089/thy.2013.0370. Epub 2014 Mar 4.
- Derived from this study: PubMed 34961921Huo Y, Xie J, Chen S, Wang H, Ma C. Recombinant human thyrotropin (rhTSH)-aided radioiodine treatment for non-toxic multinodular goitre. Cochrane Database Syst Rev. 2021 Dec 28;12(12):CD010622. doi: 10.1002/14651858.CD010622.pub2.
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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.
Medical Monitor study director
Genzyme, a Sanofi Company
11 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MRrhTSH in people with Multinodular Goiter, run by Genzyme, a Sanofi Company at 11 sites in 8 countries.
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 12 inclusion and 23 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 7 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in Brazil, Canada, Italy, United States, Denmark and 3 more countries. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Change from baseline to 6 months in goiter size by computer tomography (CT) scan. (time frame: Duration of core study). The study lists 2 primary outcomes in all. 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 NCT00454220, which also lists 2 linked publications.
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 7 Jun 2022.