Selenium Supplementation Versus Placebo in Patients With Graves' Hyperthyroidism (GRASS)

• ClinicalTrials.gov Identifier: NCT01611896
• Recruitment Status: Unknown
• First Posted: June 5, 2012
• Last Update Posted: December 23, 2020
• Sponsor: Rigshospitalet, Denmark
• Collaborators: Odense University Hospital; Hospital of South West Jutland; 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
• Information provided by (Responsible Party): Per Cramon, Rigshospitalet, Denmark

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
Graves' Hyperthyroidism	Dietary Supplement: Selenium; Other: Placebo	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 431 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Study Start Date: October 2012
• Estimated Primary Completion Date: August 2021
• Estimated Study Completion Date: August 2021

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 Name: 'Selen, organisk selen', produced by Jemo-Pharm A/S
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 :

1. 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.

Secondary Outcome Measures :

1. 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 ]
2. 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 ]
3. 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) ]
4. 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) ]
5. 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) ]
6. Hyperthyroid symptoms (ThyPRO subscale) during first year after randomisation [ Time Frame: First year after randomisation ]
7. 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) ]
8. Number of participants with adverse reactions during the intervention period [ Time Frame: 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.
9. Number of participants with serious adverse events during the intervention period [ Time Frame: 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

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Denmark

Department of Endocrinology and Gastroenterology, Bispebjerg Hospital

Copenhagen, Denmark

Department of Medical Endocrinology, Rigshospitalet

Copenhagen, Denmark

Department of Endocrinology, Hospital of Southwest Denmark

Esbjerg, Denmark

Department of Medicine, Gentofte Hospital

Gentofte, Denmark

Department of Internal Medicine O 106, Endocrine Unit, Herlev Hospital

Herlev, Denmark

Department of Cardiology and Endocrinology, Endocrine Unit, Hillerød Hospital

Hillerød, Denmark

Department of Endocrinology, Section 541, Hvidovre Hospital

Hvidovre, Denmark

Department of Endocrinology and Metabolism, Odense University Hospital

Odense, Denmark

Sponsors and Collaborators

Rigshospitalet, Denmark

Odense University Hospital

Hospital of South West Jutland

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Cramon 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.

Watt 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.

• Responsible Party: Per Cramon, Principal Investigator, Rigshospitalet, Denmark
• ClinicalTrials.gov Identifier: NCT01611896
• Other Study ID Numbers: H-4-2012-026; GRASS-DP-240 ( Other Identifier: Copenhagen Trial Unit ); 2007-58-0015, 30-0770 ( Other Identifier: Danish Data Protection Agency ); H-4-2012-026 ( Other Identifier: Regional Research Ethical Committee for the Capital Region )
• First Posted: June 5, 2012
• Last Update Posted: December 23, 2020
• Last Verified: December 2020

Keywords provided by Per Cramon, Rigshospitalet, Denmark:

Graves' hyperthyroidism; Graves' disease; Selenium; Quality of Life; ThyPRO; Autoimmunity

Additional relevant MeSH terms:

Hyperthyroidism; Thyroid Diseases; Endocrine System Diseases; Selenium; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents; Physiological Effects of Drugs; Trace Elements; Micronutrients