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

Primary Purpose

Graves' Hyperthyroidism

Status
Unknown status
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Selenium
Placebo
Sponsored by
Rigshospitalet, Denmark
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Graves' Hyperthyroidism focused on measuring Graves' hyperthyroidism, Graves' disease, Selenium, Quality of Life, ThyPRO, Autoimmunity

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Department of Endocrinology and Gastroenterology, Bispebjerg Hospital
  • Department of Medical Endocrinology, Rigshospitalet
  • Department of Endocrinology, Hospital of Southwest Denmark
  • Department of Medicine, Gentofte Hospital
  • Department of Internal Medicine O 106, Endocrine Unit, Herlev Hospital
  • Department of Cardiology and Endocrinology, Endocrine Unit, Hillerød Hospital
  • Department of Endocrinology, Section 541, Hvidovre Hospital
  • Department of Endocrinology and Metabolism, Odense University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Selenium

Placebo

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Proportion of participants who receives ATD treatment (at any level) during the 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
Proportion of participants who has been referred to ablative therapy (radioactive iodine or thyroid surgery) at some point during the entire intervention period
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
Level of TRAb at 18 months, and at the end of the intervention period (24-30 months)
Hyperthyroid symptoms (ThyPRO subscale) during first year after randomisation
Eye symptoms (ThyPRO subscale) during 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.
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.

Full Information

First Posted
May 29, 2012
Last Updated
December 22, 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
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1. Study Identification

Unique Protocol Identification Number
NCT01611896
Brief Title
Selenium Supplementation Versus Placebo in Patients With Graves' Hyperthyroidism
Acronym
GRASS
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 Type
Interventional

2. Study Status

Record Verification Date
December 2020
Overall Recruitment Status
Unknown status
Study Start Date
October 2012 (undefined)
Primary Completion Date
August 2021 (Anticipated)
Study Completion Date
August 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the 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

4. Oversight

Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Graves' Hyperthyroidism
Keywords
Graves' hyperthyroidism, Graves' disease, Selenium, Quality of Life, ThyPRO, Autoimmunity

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
431 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Selenium
Arm Type
Active Comparator
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Dietary Supplement
Intervention Name(s)
Selenium
Other Intervention Name(s)
'Selen, organisk selen', produced by Jemo-Pharm A/S
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
Proportion of participants with the composite outcome of 'ATD treatment failure'
Description
'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 Outcome Measure Information:
Title
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
Title
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
Title
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)
Title
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)
Title
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)
Title
Hyperthyroid symptoms (ThyPRO subscale) during first year after randomisation
Time Frame
First year after randomisation
Title
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)
Title
Number of participants with adverse reactions during the intervention period
Description
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)
Title
Number of participants with serious adverse events during the intervention period
Description
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)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Aase K Rasmussen, DMSc
Organizational Affiliation
Department of Medical Endocrinology, Rigshospitalet
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Torquil Watt, Ph.D.
Organizational Affiliation
Department of Medical Endocrinology, Rigshospitalet
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Laszlo Hegedüs, DMSc
Organizational Affiliation
Department of Endocrinology and Metabolism, Odense University Hospital
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Steen J Bonnema, Ph.D.
Organizational Affiliation
Department of Endocrinology and Metabolism, Odense University Hospital
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Jeppe Gram, Ph.D.
Organizational Affiliation
Department of Endocrinology, Hospital of Southwest Denmark
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Christian Gluud, DMSc
Organizational Affiliation
Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Jakob B Bjorner, Ph.D.
Organizational Affiliation
National Research Centre for the Working Environment, and Institue of Public Health Science, University of Copenhagen
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Per Cramon, MD
Organizational Affiliation
Department of Medical Endocrinology, Rigshospitalet
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Endocrinology and Gastroenterology, Bispebjerg Hospital
City
Copenhagen
Country
Denmark
Facility Name
Department of Medical Endocrinology, Rigshospitalet
City
Copenhagen
Country
Denmark
Facility Name
Department of Endocrinology, Hospital of Southwest Denmark
City
Esbjerg
Country
Denmark
Facility Name
Department of Medicine, Gentofte Hospital
City
Gentofte
Country
Denmark
Facility Name
Department of Internal Medicine O 106, Endocrine Unit, Herlev Hospital
City
Herlev
Country
Denmark
Facility Name
Department of Cardiology and Endocrinology, Endocrine Unit, Hillerød Hospital
City
Hillerød
Country
Denmark
Facility Name
Department of Endocrinology, Section 541, Hvidovre Hospital
City
Hvidovre
Country
Denmark
Facility Name
Department of Endocrinology and Metabolism, Odense University Hospital
City
Odense
Country
Denmark

12. IPD Sharing Statement

Citations:
PubMed Identifier
24519964
Citation
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.
Results Reference
derived
PubMed Identifier
23782950
Citation
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.
Results Reference
derived

Learn more about this trial

Selenium Supplementation Versus Placebo in Patients With Graves' Hyperthyroidism

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