Selenium Supplementation Versus Placebo in Patients With Graves' Hyperthyroidism

Study Overview
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Brief Summary
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The purpose of this study is to investigate if selenium supplementation to the standard treatment with anti-thyroid drugs in patients with Graves' hyperthyroidism, will lead to a fewer people with anti-thyroid treatment failure and faster remission, in terms of better quality of life during the first year of treatment and more patients staying in remission.

Official Title
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GRAves Selenium Supplementation Trial (GRASS) - an Investigator-initiated Randomised, Blinded, Multicentre Clinical Trial of Selenium Supplementation Versus Placebo in Patients With Graves' Hyperthyroidism

Conditions
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Graves' Hyperthyroidism

Intervention / Treatment
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* Dietary Supplement: Selenium
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or older. Active Graves' hyperthyroidism (suppressed TSH (< 0.1) and positive TRAb) measured within the last two months prior to the inclusion date. Written informed consent Exclusion Criteria: Major co-morbidity, making the participants unlikely to continuously receive trial intervention in the intervention period. Previous treatment with radioactive iodine. Current ATD treatment having been received for more than two months. Treatment with immunomodulatory drugs, such as cyclosporine A, methotrexate, cyclophosphamide. Allergy towards the components in the selenium and placebo pills. Pregnant or breast-feeding women. Intake of selenium supplementation above 70 µg per day (70 µg corresponds to the amount in a multivitamin tablet). Unable to read and understand Danish. Lack of informed consent

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: Selenium<br> | Dietary Supplement: Selenium<br>* 100 µg tablets. The dose of daily supplement of selenium is set at 200 µg (two tablets). The duration of the intervention period is between 24-30 months. This is defined by the time of ATD treatment withdrawal, which is scheduled between approximately 12-18 months after randomisation. Selenium supplementation will continue 12 months after withdrawal of ATD treatment.<br>* Other names: 'Selen, organisk selen', produced by Jemo-Pharm A/S;|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Placebo tablets, identical in regards to size, appearance, taste, smell, and solubility to the experimental intervention tablet will be produced by Jemo-Pharm A/S, http://www.jemo-pharm.dk/frame.cfm/cms/id=977/sprog=2/grp=6/menu=1/ (content as in section: Auxiliary agents). The placebo regimen will be identical to the selenium regimen, but consist of two non-active tablets per day for 24-30 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with the composite outcome of 'ATD treatment failure' | 'ATD treatment failure' is defined as: The participant receives ATD treatment (at any level) during the last 12 months (± 1 month) of the intervention period; or The participant has thyroid hyperfunction (TSH <0.1) during the last 12 months (± 1 month) of the intervention period; or The participant has been referred to ablative therapy (radioactive iodine or thyroid surgery) at some point during the entire intervention period. | Last 12 months (± 1 month) of the intervention period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants who receives ATD treatment (at any level) during the last 12 months (± 1 month) of the intervention period |  | Last 12 months (± 1 month) of the intervention period | 
| Proportion of participants who has thyroid hyperfunction (TSH <0.1) during the last 12 months (± 1 month) of the intervention period |  | Last 12 months (± 1 month) of the intervention period | 
| Proportion of participants who has been referred to ablative therapy (radioactive iodine or thyroid surgery) at some point during the entire intervention period |  | Intervention period (24-30 months) | 
| Thyroid-specific QoL during the first year after randomisation, and at the end of the intervention period (24-30 months), as measured by the global score in the ThyPRO questionnaire |  | First year after randomisation, and at the end of the intervention period (24-30 months) | 
| Level of TRAb at 18 months, and at the end of the intervention period (24-30 months) |  | 18 months, and at the end of the intervention period (24-30 months) | 
| Hyperthyroid symptoms (ThyPRO subscale) during first year after randomisation |  | First year after randomisation | 
| Eye symptoms (ThyPRO subscale) during first year after randomisation, and at end of the intervention period (24-30 months) |  | First year after randomisation, and at end of the intervention period (24-30 months) | 
| Number of participants with adverse reactions during the intervention period | Participants will be asked to report about known adverse reactions (specified in the protocol) at 6 weeks, 12 weeks, 6 months, 12 months, 18 months, 24 months, and 12 months after ATD treatment withdrawal. In addition, participants are instructed to contact their trial contact person in case they experience adverse reactions. | Intervention period (24-30 months) | 
| Number of participants with serious adverse events during the intervention period | To make sure we get information on serious adverse events, data on hospital admissions and mortality will be obtained through the national databases (the National Patient Registry and the Danish Civil Registration System) at the end of the trial. Also, participants are informed and instructed to contact their trial contact person in case they: are admitted to a hospital for selenium intoxication; experience a clinical picture indicative of selenium intoxication; or experience a clinical picture unexpected, but suspected to be related to selenium intoxication. | Intervention period (24-30 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Graves' hyperthyroidism, Graves' disease, Selenium, Quality of Life, ThyPRO, Autoimmunity