Graves' HyperthyroidismGRASSNCT01611896
Selenium Supplementation Versus Placebo in Patients With Graves' Hyperthyroidism
A study testing Selenium in people with Graves' Hyperthyroidism, run by Copenhagen University Hospital, Rigshospitalet at 8 sites in Denmark.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Graves' Hyperthyroidism
- What is being tested?
- Selenium
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 431 participants
- Where
- 8 sitesDenmark
- Study dates
- Oct 2012to Aug 2024
- Phase
- Interventional
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 9Show fewer
- 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
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
Denmark8 sites
Department of Endocrinology and Gastroenterology, Bispebjerg Hospital
Copenhagen
Department of Medical Endocrinology, Rigshospitalet
Copenhagen
Department of Endocrinology, Hospital of Southwest Denmark
Esbjerg
Department of Medicine, Gentofte Hospital
Gentofte Municipality
Department of Internal Medicine O 106, Endocrine Unit, Herlev Hospital
Herlev
Department of Cardiology and Endocrinology, Endocrine Unit, Hillerød Hospital
Hillerød
Department of Endocrinology, Section 541, Hvidovre Hospital
Hvidovre
Department of Endocrinology and Metabolism, Odense University Hospital
Odense
About this study
Official title: GRAves Selenium Supplementation Trial (GRASS) - an Investigator-initiated Randomised, Blinded, Multicentre Clinical Trial of Selenium Supplementation Versus Placebo in Patients With Graves' Hyperthyroidism
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.
- Conditions
- Graves' Hyperthyroidism
- Being tested
- Selenium, Placebo
- Keywords
- Graves' hyperthyroidism, Graves' disease, Selenium, Quality of Life, ThyPRO, Autoimmunity
- Medical subject headings
- Graves Disease, Autoimmune Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SeleniumDietary supplement
Also called 'Selen, organisk selen', produced by Jemo-Pharm A/S
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.
PlaceboOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Selenium | Active comparator | Not described Receives: Dietary Supplement: Selenium |
| Placebo | Placebo comparator | Not described Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Last 12 months (± 1 month) of the intervention period
Secondary outcomes (9)
Proportion of participants who receives ATD treatment (at any level) during the last 12 months (± 1 month) of the intervention period
Measured: 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
Measured: 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
Measured: 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
Measured: 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)
Measured: 18 months, and at the end of the intervention period (24-30 months)
Hyperthyroid symptoms (ThyPRO subscale) during first year after randomisation
Measured: First year after randomisation
Eye symptoms (ThyPRO subscale) during first year after randomisation, and at end of the intervention period (24-30 months)
Measured: 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.
Measured: 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.
Measured: Intervention period (24-30 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2012 (estimated)
- Study startOct 2012
- Primary completionJun 2021
- Study completionAug 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Graves' HyperthyroidismStudies of the same condition, open and under way.
- More trials run by Copenhagen University Hospital, RigshospitaletThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 431 participants (actual)
Sponsor and investigators
- Lead sponsor
- Copenhagen University Hospital, Rigshospitalet
- Sponsor type
- University, hospital or other
- Collaborators
- Odense University Hospital, Esbjerg Hospital - University Hospital of Southern 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
- Responsible party
- Principal investigator, Per Cramon, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Aase K Rasmussen, DMSc, Study chair, Department of Medical Endocrinology, RigshospitaletTorquil Watt, Ph.D., Study chair, Department of Medical Endocrinology, RigshospitaletLaszlo Hegedüs, DMSc, Study chair, Department of Endocrinology and Metabolism, Odense University HospitalSteen J Bonnema, Ph.D., Study chair, Department of Endocrinology and Metabolism, Odense University HospitalJeppe Gram, Ph.D., Study chair, Department of Endocrinology, Hospital of Southwest DenmarkChristian Gluud, DMSc, Study chair, Copenhagen Trial Unit, Centre for Clinical Intervention Research, RigshospitaletJakob B Bjorner, Ph.D., Study chair, National Research Centre for the Working Environment, and Institue of Public Health Science, University of CopenhagenPer Cramon, MD, Principal investigator, Department of Medical Endocrinology, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01611896
- Sponsor's protocol ID
- H-4-2012-026
- Other IDs
- GRASS-DP-240, 2007-58-0015, 30-0770, H-4-2012-026
- Acronym
- GRASS
- Status last verified
- Feb 2025
- First submitted
- 29 May 2012
- Last updated
- 13 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Cramon PK, Winther KH, Boesen VB, Larsen CB, Bjorner JB, Nordqvist SF, Forman JL, Juul AB, Bach-Mortensen P, Knudsen N, Nolsoe RL, Vilsboll T, Andries A, Gram J, Nygaard B, Demircan K, Chillon TS, Schomburg L, Hegedus L, Bonnema SJ, Feldt-Rasmussen U, Rasmussen AK, Watt T. Selenium supplementation in individuals with newly diagnosed Graves' hyperthyroidism: a double-blind, multi-centre RCT. Eur Thyroid J. 2026 Jan 6;15(1):ETJ250264. doi: 10.1530/ETJ-25-0264. Print 2026 Jan 1.
PubMed 41384622Cramon P, Rasmussen AK, Bonnema SJ, Bjorner JB, Feldt-Rasmussen U, Groenvold M, Hegedus L, Watt T. Development and implementation of PROgmatic: A clinical trial management system for pragmatic multi-centre trials, optimised for electronic data capture and patient-reported outcomes. Clin Trials. 2014 Jun;11(3):344-354. doi: 10.1177/1740774513517778.
PubMed 24519964Watt T, Cramon P, Bjorner JB, Bonnema SJ, Feldt-Rasmussen U, Gluud C, Gram J, Hansen JL, Hegedus L, Knudsen N, Bach-Mortensen P, Nolsoe R, Nygaard B, Pociot F, Skoog M, Winkel P, Rasmussen AK. Selenium supplementation for patients with Graves' hyperthyroidism (the GRASS trial): study protocol for a randomized controlled trial. Trials. 2013 Apr 30;14:119. doi: 10.1186/1745-6215-14-119.
PubMed 23782950
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- GRAves Selenium Supplementation Trial (GRASS) - an Investigator-initiated Randomised, Blinded, Multicentre Clinical Trial of Selenium Supplementation Versus Placebo in Patients With Graves' Hyperthyroidism
- ClinicalTrials.gov ID
- NCT01611896
- Acronym / sponsor ID
- GRASS / H-4-2012-026
- Conditions
- Graves' Hyperthyroidism
- Keywords
- Graves' hyperthyroidism, Graves' disease, Selenium, Quality of Life, ThyPRO, Autoimmunity
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 431 participants (actual)
- Lead sponsor
- Copenhagen University Hospital, RigshospitaletUniversity, hospital or other
- Collaborators
- Odense University Hospital, Esbjerg Hospital - University Hospital of Southern 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
- Study start
- Oct 2012 (actual)
- Primary completion
- Jun 2021 (actual)
- Study completion
- Aug 2024 (actual)
- First posted
- 5 Jun 2012 (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 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Selenium | Active comparator | Dietary Supplement: Selenium |
| Placebo | Placebo comparator | Other: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (9 listed)
- 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.
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 |
|---|---|---|
| SeleniumAlso: 'Selen, organisk selen', produced by Jemo-Pharm A/S100 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. | Dietary supplement | Selenium |
| PlaceboPlacebo 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. | Other | Placebo |
Primary outcome
Proportion of participants with the composite outcome of 'ATD treatment failure'
Time frame: 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.
9 secondary outcomes
Proportion of participants who receives ATD treatment (at any level) during the last 12 months (± 1 month) of the intervention period
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 18 months, and at the end of the intervention period (24-30 months)
Hyperthyroid symptoms (ThyPRO subscale) during first year after randomisation
Time frame: First year after randomisation
Eye symptoms (ThyPRO subscale) during first year after randomisation, and at end of the intervention period (24-30 months)
Time frame: First year after randomisation, and at end of the intervention period (24-30 months)
Number of participants with adverse reactions during the intervention period
Time frame: Intervention period (24-30 months)
Number of participants with serious adverse events during the intervention period
Time frame: Intervention period (24-30 months)
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 13 Feb 2025.
- Derived from this study: PubMed 41384622Cramon PK, Winther KH, Boesen VB, Larsen CB, Bjorner JB, Nordqvist SF, Forman JL, Juul AB, Bach-Mortensen P, Knudsen N, Nolsoe RL, Vilsboll T, Andries A, Gram J, Nygaard B, Demircan K, Chillon TS, Schomburg L, Hegedus L, Bonnema SJ, Feldt-Rasmussen U, Rasmussen AK, Watt T. Selenium supplementation in individuals with newly diagnosed Graves' hyperthyroidism: a double-blind, multi-centre RCT. Eur Thyroid J. 2026 Jan 6;15(1):ETJ250264. doi: 10.1530/ETJ-25-0264. Print 2026 Jan 1.
- Derived from this study: PubMed 24519964Cramon P, Rasmussen AK, Bonnema SJ, Bjorner JB, Feldt-Rasmussen U, Groenvold M, Hegedus L, Watt T. Development and implementation of PROgmatic: A clinical trial management system for pragmatic multi-centre trials, optimised for electronic data capture and patient-reported outcomes. Clin Trials. 2014 Jun;11(3):344-354. doi: 10.1177/1740774513517778.
- Derived from this study: PubMed 23782950Watt T, Cramon P, Bjorner JB, Bonnema SJ, Feldt-Rasmussen U, Gluud C, Gram J, Hansen JL, Hegedus L, Knudsen N, Bach-Mortensen P, Nolsoe R, Nygaard B, Pociot F, Skoog M, Winkel P, Rasmussen AK. Selenium supplementation for patients with Graves' hyperthyroidism (the GRASS trial): study protocol for a randomized controlled trial. Trials. 2013 Apr 30;14:119. doi: 10.1186/1745-6215-14-119.
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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.
Aase K Rasmussen, DMSc study chair
Department of Medical Endocrinology, Rigshospitalet
Torquil Watt, Ph.D. study chair
Department of Medical Endocrinology, Rigshospitalet
Laszlo Hegedüs, DMSc study chair
Department of Endocrinology and Metabolism, Odense University Hospital
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Selenium in people with Graves' Hyperthyroidism, run by Copenhagen University Hospital, Rigshospitalet at 8 sites 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 3 inclusion and 9 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 13 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites 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. 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.
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?
Proportion of participants with the composite outcome of 'ATD treatment failure' (time frame: Last 12 months (± 1 month) of the intervention period). 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 NCT01611896, which also lists 3 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 13 Feb 2025; AzTrials last refreshed its copy on 30 Oct 2026.