rhTSH, Radioiodine Uptake and Goiter Reduction Following 131I Therapy in Patients With Benign Nontoxic Nodular Goiter

Study Overview
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Brief Summary
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The study aims at clarifying (in a randomized, double-blinded design): Whether stimulation with 0.1 mg rhTSH 24, 48 or 72 hours before induction of a 131I-tracer dosis increases the 131I uptake in patients with atoxic multinodular goitre and to study which time interval is the most optimal (Part I) Whether patients suffering from atoxic multinodular goitre obtains a corresponding goitre reduction compared with a control group when stimulating with 0.1 mg rh TSH 24, 48 or 72 hours before 131I therapy and when reducing the thyroid radiation dose to 50 Gy (Part II) The two studies will be carried out successively on the same patient population. The 131I uptake will be carried out first followed by the I therapy itself. The patients are compared with a placebo-treated control group going through the same course of treatment, but the 131I dosis will be 100 Gy (standard treatment). After the 131I therapy, all patients are followed during one year with a regular ultrasound scan of the thyroid gland and control of the metabolic status. The patient satisfaction is monitored by the use of a visual-analogue-scale.

Official Title
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The Effect of 0.1 mg Recombinant Human Thyrotropin (rhTSH) on Thyroid Radioiodine-uptake and the Degree of Goiter Reduction Following 131I-therapy, in Patients With Benign Non-toxic Nodular Goiter. A Randomized, Double-blind, Placebo-controlled Trial.

Conditions
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Nodular Goiter

Intervention / Treatment
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* Drug: Recombinant human thyrotropin (Thyrogen)
* Drug: recombinant human TSH
* Other: isotonic saline = placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age over 18 years Apart from benign non-toxic goiter no other serious illness Signed proof of participation Exclusion Criteria: Treatment with Levothyroxine Former 131I-therapy A thyroid volume above 100 ml or a retro-clavicular component Unsafe contraception Pregnancy or breastfeeding Participation in another clinical trial Previous allergic reaction toward rhTSH Suspicion of malignancy in the thyroid gland either by clinical examination, laboratory findings (a raised serum calcitonin or ionized calcium)or by fine-needle aspiration biopsy Physically or mental condition making it impossible to participate Acute ischemic heart attach within the last 3 months Alcohol and/or drug addicts

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: rhTSH<br>proceeded by 0.1 mg rhTSH | Drug: Recombinant human thyrotropin (Thyrogen)<br>* 0.1 mg rhTSH administered intramuscularly<br>Drug: recombinant human TSH<br>* 0.1 mg rhTSH administered intramuscularly<br>|
| Placebo Comparator: Placebo<br>1 ml isotonic saline | Other: isotonic saline = placebo<br>* 0.1 mg isotonic saline injected intramuscularly<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| An intra-individual comparison of the thyroid 131I-uptake before and after stimulation with rhTSH /placebo |  | 24 and 96 hours after tracer administration | 
| An inter-individual comparison of the thyroid 131I uptake between those who receive placebo and those who receive rhTSH |  | 24 and 96 hours after tracer administration | 
| An estimation of which time-interval, injecting rhTSH, that is more favourable before 131I therapy (24 hours, 48 hours or 72 hours) |  | 24 and 96 hours after tracer administration | 
| A comparison of the degree of goiter reduction when patients are prestimulated with rhTSH and receive a thyroid 131I dose of 50 Gy or when receiving conventional 131I, receiving a thyroid dose of 100 Gy |  | 3, 6, 9 and 12 months after 131I therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A registration of adverse effects following rhTSH/placebo |  | All adverse effects occuring within one year follow-up | 
| Patient satisfaction (Visual Analogue Scale) before, 3 months post 131I therapy, and at the end of follow-up (1 year). |  | baseline, 3 and 12 months after 131I therapy | 
| Development of TPOab or TSHRab |  | At 12 months follow-up | 
| Thyroid function |  | At 12 months follow up. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nontoxic nodular goiter, 131I therapy, thyroid radioiodine uptake, optimal time-interval, reduced 131I activity, goiter reduction