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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Rigshospitalet, Denmark
Sponsor:
Collaborators:
Odense University Hospital
Hospital of South West 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
Information provided by (Responsible Party):
Per Cramon, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier:
NCT01611896
First received: May 29, 2012
Last updated: May 2, 2014
Last verified: May 2014
  Purpose

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 Intervention
Graves' Hyperthyroidism
Dietary Supplement: Selenium
Other: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Rigshospitalet, Denmark:

Primary Outcome Measures:
  • Proportion of participants with the composite outcome of 'ATD treatment failure' [ Time Frame: Last 12 months (± 1 month) of the intervention period ] [ Designated as safety issue: No ]

    '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 [ Time Frame: Last 12 months (± 1 month) of the intervention period ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • Hyperthyroid symptoms (ThyPRO subscale) during first year after randomisation [ Time Frame: First year after randomisation ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • Number of participants with adverse reactions during the intervention period [ Time Frame: Intervention period (24-30 months) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Intervention period (24-30 months) ] [ Designated as safety issue: No ]

    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.


Estimated Enrollment: 492
Study Start Date: October 2012
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01611896

Contacts
Contact: Per Cramon, MD (+45) 51 68 45 33 per.cramon@rh.regionh.dk
Contact: Torquil Watt, Ph.D. (+45) 35 45 10 97 torquil.watt@rh.regionh.dk

Locations
Denmark
Department of Medical Endocrinology, Rigshospitalet Recruiting
Copenhagen, Denmark
Principal Investigator: Per Cramon, MD         
Sub-Investigator: Ulla Feldt-Rasmussen, DMSc         
Sub-Investigator: Torquil Watt, Ph.D.         
Sub-Investigator: Aase K Rasmussen, DMSc         
Department of Endocrinology and Gastroenterology, Bispebjerg Hospital Recruiting
Copenhagen, Denmark
Principal Investigator: Nils Knudsen, Ph.D., DMSc         
Department of Endocrinology, Hospital of Southwest Denmark Recruiting
Esbjerg, Denmark
Principal Investigator: Jeppe Gram, Ph.D.         
Department of Medicine, Gentofte Hospital Recruiting
Gentofte, Denmark
Principal Investigator: Tina Vilsbøll, DMSc         
Department of Internal Medicine O 106, Endocrine Unit, Herlev Hospital Recruiting
Herlev, Denmark
Principal Investigator: Birte Nygaard, Ph.D.         
Department of Cardiology and Endocrinology, Endocrine Unit, Hillerød Hospital Recruiting
Hillerød, Denmark
Principal Investigator: Runa Nolsøe, Ph.D.         
Department of Endocrinology, Section 541, Hvidovre Hospital Recruiting
Hvidovre, Denmark
Principal Investigator: Pernille Bach-Mortensen, Ph.D.         
Department of Endocrinology and Metabolism, Odense University Hospital Recruiting
Odense, Denmark
Principal Investigator: Steen J Bonnema, Ph.D.         
Sub-Investigator: Laszlo Hegedüs, DMSc         
Sub-Investigator: Kristian Winther, MD         
Sponsors and Collaborators
Rigshospitalet, Denmark
Odense University Hospital
Hospital of South West 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
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

No publications provided by Rigshospitalet, Denmark

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Per Cramon, Principal Investigator, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT01611896     History of Changes
Other Study ID Numbers: H-4-2012-026, GRASS-DP-240, 2007-58-0015, 30-0770, H-4-2012-026
Study First Received: May 29, 2012
Last Updated: May 2, 2014
Health Authority: Denmark: Regional Research Ethical Committee for the Capital Region
Denmark: Danish Dataprotection Agency

Keywords provided by Rigshospitalet, Denmark:
Graves' hyperthyroidism
Graves' disease
Selenium
Quality of Life
ThyPRO
Autoimmunity

Additional relevant MeSH terms:
Graves Disease
Hyperthyroidism
Thyroid Diseases
Endocrine System Diseases
Exophthalmos
Orbital Diseases
Eye Diseases
Goiter
Autoimmune Diseases
Immune System Diseases
Selenium
Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents

ClinicalTrials.gov processed this record on July 29, 2014