Selenium Supplementation Versus Placebo in Patients With Graves' Hyperthyroidism

NCT01611896 | Completed DMC

• 3 other identifiers: H-4-2012-026GRASS-DP-2402007-58-0015, 30-0770
• Study Type: interventional
• Target: 431
• Locations: 1 country
• Sites: 8

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.

Conditions

Graves' Hyperthyroidism

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• 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)

Study Arms (2)

Selenium

ACTIVE COMPARATOR

Dietary Supplement: Selenium

Placebo

PLACEBO COMPARATOR

Other: Placebo

Interventions

Selenium DIETARY_SUPPLEMENT

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.

Also known as: 'Selen, organisk selen', produced by Jemo-Pharm A/S

Selenium

Placebo OTHER

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.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years or older.
• Written informed consent

You may not qualify if:

• 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

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead
• Odense University Hospital: collaborator
• Esbjerg Hospital - University Hospital of Southern Denmark: collaborator
• Herlev Hospital: collaborator
• Bispebjerg Hospital: collaborator
• Hvidovre University Hospital: collaborator
• Hillerod Hospital, Denmark: collaborator
• Copenhagen Trial Unit, Center for Clinical Intervention Research: collaborator
• Danish Council for Independent Research: collaborator
• The Danish Council for Strategic Research: collaborator

Study Sites (8)

Department of Endocrinology and Gastroenterology, Bispebjerg Hospital

Copenhagen, Denmark

Location

Department of Medical Endocrinology, Rigshospitalet

Copenhagen, Denmark

Location

Department of Endocrinology, Hospital of Southwest Denmark

Esbjerg, Denmark

Location

Department of Medicine, Gentofte Hospital

Gentofte Municipality, Denmark

Location

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

Herlev, Denmark

Location

Department of Cardiology and Endocrinology, Endocrine Unit, Hillerød Hospital

Hillerød, Denmark

Location

Department of Endocrinology, Section 541, Hvidovre Hospital

Hvidovre, Denmark

Location

Department of Endocrinology and Metabolism, Odense University Hospital

Odense, Denmark

Location

Related Publications (3)

• 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.

  PMID: 41384622 DERIVED

• 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.

  PMID: 24519964 DERIVED

• 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.

  PMID: 23782950 DERIVED

MeSH Terms

Conditions

Graves Disease; Autoimmune Diseases

Interventions

Selenium

Condition Hierarchy (Ancestors)

Exophthalmos; Orbital Diseases; Eye Diseases; Goiter; Thyroid Diseases; Endocrine System Diseases; Hyperthyroidism; Immune System Diseases

Intervention Hierarchy (Ancestors)

Chalcogens; Elements; Inorganic Chemicals; Minerals

Study Officials

• 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

  STUDY CHAIR

• Per Cramon, MD

  Department of Medical Endocrinology, Rigshospitalet

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 29, 2012
• First Posted: June 5, 2012
• Study Start: October 1, 2012
• Primary Completion: June 1, 2021
• Study Completion: August 1, 2024
• Last Updated: February 13, 2025

Record last verified: 2025-02

Locations

DK (8)