Clinical trial NCT01611896: Selenium Supplementation Versus Placebo in Patients With Graves' Hyperthyroidism
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
Overall status: COMPLETED
Phase: NA
Conditions: Graves' Hyperthyroidism
Keywords: Graves' hyperthyroidism
Graves' disease
Selenium
Quality of Life
ThyPRO
Autoimmunity
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: Odense University Hospital
name: Esbjerg Hospital - University Hospital of Southern Denmark
name: Herlev Hospital
name: Bispebjerg Hospital
name: Hvidovre University Hospital
name: Hillerod Hospital, Denmark
name: Copenhagen Trial Unit, Center for Clinical Intervention Research
name: Danish Council for Independent Research
name: The Danish Council for Strategic Research
First posted: 2012-06-05
Enrollment: 431
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Proportion of participants with the composite outcome of 'ATD treatment failure'
timeFrame: Last 12 months (± 1 month) of the intervention period
Secondary outcomes:
measure: Proportion of participants who receives ATD treatment (at any level) during the last 12 months (± 1 month) of the intervention period
timeFrame: Last 12 months (± 1 month) of the intervention period
measure: Proportion of participants who has thyroid hyperfunction (TSH <0.1) during the last 12 months (± 1 month) of the intervention period
timeFrame: Last 12 months (± 1 month) of the intervention period
measure: Proportion of participants who has been referred to ablative therapy (radioactive iodine or thyroid surgery) at some point during the entire intervention period
timeFrame: Intervention period (24-30 months)
measure: 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
timeFrame: First year after randomisation, and at the end of the intervention period (24-30 months)
measure: Level of TRAb at 18 months, and at the end of the intervention period (24-30 months)
timeFrame: 18 months, and at the end of the intervention period (24-30 months)
measure: Hyperthyroid symptoms (ThyPRO subscale) during first year after randomisation
timeFrame: First year after randomisation
measure: Eye symptoms (ThyPRO subscale) during first year after randomisation, and at end of the intervention period (24-30 months)
timeFrame: First year after randomisation, and at end of the intervention period (24-30 months)
measure: Number of participants with adverse reactions during the intervention period
timeFrame: Intervention period (24-30 months)
measure: Number of participants with serious adverse events during the intervention period
timeFrame: Intervention period (24-30 months)
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Department of Endocrinology and Gastroenterology, Bispebjerg Hospital
city: Copenhagen
country: Denmark
facility: Department of Medical Endocrinology, Rigshospitalet
city: Esbjerg
country: Denmark
facility: Department of Endocrinology, Hospital of Southwest Denmark
city: Gentofte
country: Denmark
facility: Department of Medicine, Gentofte Hospital
city: Herlev
country: Denmark
facility: Department of Internal Medicine O 106, Endocrine Unit, Herlev Hospital
city: Hillerød
country: Denmark
facility: Department of Cardiology and Endocrinology, Endocrine Unit, Hillerød Hospital
city: Hvidovre
country: Denmark
facility: Department of Endocrinology, Section 541, Hvidovre Hospital
city: Odense
country: Denmark
facility: Department of Endocrinology and Metabolism, Odense University Hospital
Study officials:
affiliation: Department of Medical Endocrinology, Rigshospitalet
name: Aase K Rasmussen, DMSc
role: STUDY_CHAIR
affiliation: Department of Medical Endocrinology, Rigshospitalet
name: Torquil Watt, Ph.D.
role: STUDY_CHAIR
affiliation: Department of Endocrinology and Metabolism, Odense University Hospital
name: Laszlo Hegedüs, DMSc
role: STUDY_CHAIR
affiliation: Department of Endocrinology and Metabolism, Odense University Hospital
name: Steen J Bonnema, Ph.D.
role: STUDY_CHAIR
affiliation: Department of Endocrinology, Hospital of Southwest Denmark
name: Jeppe Gram, Ph.D.
role: STUDY_CHAIR
affiliation: Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet
name: Christian Gluud, DMSc
role: STUDY_CHAIR
affiliation: National Research Centre for the Working Environment, and Institue of Public Health Science, University of Copenhagen
name: Jakob B Bjorner, Ph.D.
role: STUDY_CHAIR
affiliation: Department of Medical Endocrinology, Rigshospitalet
name: Per Cramon, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.