GRASS: Selenium Supplementation Versus Placebo in Patients With Graves' Hyperthyroidism
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Selenium
|
Dietary Supplement: Selenium
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.
Other Names:
|
| Placebo Comparator: Placebo
|
Other: Placebo
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.
|
Outcome Measures
Primary Outcome Measures
- Proportion of participants with the composite outcome of 'ATD treatment failure' [Last 12 months (± 1 month) of the intervention period]
'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.
Secondary Outcome Measures
- 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 [Intervention period (24-30 months)]
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.
- Number of participants with serious adverse events during the intervention period [Intervention period (24-30 months)]
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.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Department of Endocrinology and Gastroenterology, Bispebjerg Hospital | Copenhagen | Denmark | ||
| 2 | Department of Medical Endocrinology, Rigshospitalet | Copenhagen | Denmark | ||
| 3 | Department of Endocrinology, Hospital of Southwest Denmark | Esbjerg | Denmark | ||
| 4 | Department of Medicine, Gentofte Hospital | Gentofte | Denmark | ||
| 5 | Department of Internal Medicine O 106, Endocrine Unit, Herlev Hospital | Herlev | Denmark | ||
| 6 | Department of Cardiology and Endocrinology, Endocrine Unit, Hillerød Hospital | Hillerød | Denmark | ||
| 7 | Department of Endocrinology, Section 541, Hvidovre Hospital | Hvidovre | Denmark | ||
| 8 | Department of Endocrinology and Metabolism, Odense University Hospital | Odense | Denmark |
Sponsors and Collaborators
- Rigshospitalet, Denmark
- Odense University Hospital
- Hospital of South West Denmark
- Herlev Hospital
- Bispebjerg Hospital
- Hvidovre University Hospital
- Hillerod Hospital, Denmark
- Copenhagen Trial Unit, Center for Clinical Intervention Research
- Danish Council for Independent Research
- The Danish Council for Strategic Research
Investigators
- Study Chair: Aase K Rasmussen, DMSc, Department of Medical Endocrinology, Rigshospitalet
- Study Chair: Torquil Watt, Ph.D., Department of Medical Endocrinology, Rigshospitalet
- Study Chair: Laszlo Hegedüs, DMSc, Department of Endocrinology and Metabolism, Odense University Hospital
- Study Chair: Steen J Bonnema, Ph.D., Department of Endocrinology and Metabolism, Odense University Hospital
- Study Chair: Jeppe Gram, Ph.D., Department of Endocrinology, Hospital of Southwest Denmark
- Study Chair: Christian Gluud, DMSc, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet
- Study Chair: Jakob B Bjorner, Ph.D., National Research Centre for the Working Environment, and Institue of Public Health Science, University of Copenhagen
- Principal Investigator: Per Cramon, MD, Department of Medical Endocrinology, Rigshospitalet
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- H-4-2012-026
- GRASS-DP-240
- 2007-58-0015, 30-0770
- H-4-2012-026