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CompletedNCT01611896GRASSUpdated Feb 13, 2025

Selenium Supplementation Versus Placebo in Patients with Graves' Hyperthyroidism

An interventional study of Selenium and Placebo in Graves' Hyperthyroidism, sponsored by Rigshospitalet, Denmark. Completed at 8 sites in Denmark. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-02-13.

Sponsored by Rigshospitalet, Denmark · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
431
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

02

Conditions studied

  • Graves' Hyperthyroidism

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Keywords

  • Graves' hyperthyroidism
  • Graves' disease
  • Selenium
  • Quality of Life
  • ThyPRO
  • Autoimmunity
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
431 participants (actual)

Study arms

  • Active comparator
    Selenium

    Dietary Supplement: Selenium

  • Placebo comparator
    Placebo

    Other: Placebo

Interventions

  • Dietary supplementSelenium

    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

  • OtherPlacebo

    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.

05

What researchers measure

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.

    Time frame: Last 12 months (± 1 month) of the intervention period

Secondary outcomes

  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

    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.

    Time frame: Intervention period (24-30 months)

  9. 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.

    Time frame: Intervention period (24-30 months)

06

Study locations

8 sites
  • 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
07

References and documents

Publications

  • 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. PubMed 24519964 ↗
  • 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. PubMed 23782950 ↗
08

Registry details

Key details

Study ID
NCT01611896
Lead sponsor
Rigshospitalet, Denmark
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
Per Cramon (Principal Investigator, Rigshospitalet, Denmark) — Principal investigator
First posted
Jun 5, 2012
Start date
Oct 2012
Primary completion
Jun 2021
Completion
Aug 2024
Last update
Feb 13, 2025

Study contacts

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
Steen J Bonnema, Ph.D.
study chair · Department of Endocrinology and Metabolism, Odense University Hospital
Jeppe Gram, Ph.D.
study chair · Department of Endocrinology, Hospital of Southwest Denmark
Christian Gluud, DMSc
study chair · Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet
Jakob B Bjorner, Ph.D.
study chair · National Research Centre for the Working Environment, and Institue of Public Health Science, University of Copenhagen
Per Cramon, MD
principal investigator · Department of Medical Endocrinology, Rigshospitalet

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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