The purpose of this study is to investigate the effects of vitamin D supplementation on morbidity and risk of relapse in patients with Graves' disease.
In a multicentre trial, 260 patients with newly diagnosed Graves ' disease will be randomized to cholecalciferol 70 mcg/day or placebo in a parallel Group design. Drop outs prior to 31th of December 2017 will be replaced. The intervention will continue during treatment with antithyroid drugs (ATD), and for a period of 12 months after cessation of ATD. Blood samples will be collected at study entry, at 3 and 9 months, and at end of study. QoL questionnaires on nine occasions through out the study period. In a subcohort of 80 participants detailed examinations of bone density and geometry, muscle strength and postural balance, immune tests (N=50), and measurements of arterial stiffness will be performed at study entry, and at 3 and 9 months after randomisation.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
278
One tablet per day. The duration of the intervention period is between 24-36 months. This is defined by the time of ATD treatment withdrawal, which is scheduled between approximately 12-18(-24) months after randomisation. Vitamin D supplementation will continue 12 months after withdrawal of ATD treatment or until relapse of Graves' Disease if this occurs prior.
One tablet per day. Placebo tablet identical in appearance to cholecalciferol tablet. Duration and cessation of treatment identical to intervention with cholecalciferol.
Department of Endocrinology and Internal Medicine, Aarhus University Hospital
Aarhus C, Denmark
Gentofte Hospital
Gentofte Municipality, Denmark
Department of Internal Medicine, Regionshospitalet Herning
Herning, Denmark
Proportion of participants without relapse within the first year after cessation of ATD treatment.
A relapse is defined as: The participant has been referred to radioactive iodine or thyroid surgery at any time during the entire intervention period; or The participant has hyperthyroidism (TSH\<0.1) at 12 months (+/- 1 months) after cessation of ATD treatment; or ATD is re-initiated within 12 months after cessation of initial ATD treatment; or The participant fails to stop ATD treatment within 24 months after initiation of ATD treatment.
Time frame: 0-12 months after cessation of ATD treatment
The proportion of participants who has been referred to radioactive iodine or thyroid surgery at any time during the entire intervention period.
The proportion of participants who has been referred to radioactive iodine or thyroid surgery at any time during the entire intervention period.
Time frame: From randomisation until 12 months after cessation of ATD treatment, an expected average of 24 months
The proportion of participants who have relapse of hyperthyroidism (TSH<0.1) after cessation of ATD therapy
The proportion of participants who have relapse of hyperthyroidism (TSH\<0.1) after cessation of ATD therapy
Time frame: 0-12 months after cessation of ATD treatment
The proportion of participants who re-initiates ATD treatment or is referred to radioactive iodine or thyroid surgery due to hyperthyroidism within 12 months after cessation of initial ATD treatment.
The proportion of participants who re-initiates ATD treatment or is referred to radioactive iodine or thyroid surgery due to hyperthyroidism within 12 months after cessation of initial ATD treatment.
Time frame: 0-12 months after cessation of ATD treatment
The proportion of participants who fails to stop ATD treatment within 24 months after initiation of ATD therapy.
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Department of Internal Medicine, Regionshospitalet Holstebro
Holstebro, Denmark
Department of Internal Medicine, Regionshospitalet Horsens
Horsens, Denmark
Department of Internal Medicine, Regionhospitalet Randers
Randers, Denmark
Department of Internal Medicine, Diagnostisk Center, Regionshospitalet Silkeborg
Silkeborg, Denmark
Department of Internal Medicine, Regionshospitalet Viborg
Viborg, Denmark
In a pre-planned sub-analysis participants on sustained ATD treatment for more than 24 months after initiation of ATD therapy because of Graves' orbitopathy will be excluded
Time frame: 0-24 months after initiation of ATD therapy
Effects of D-vitamin supplementation according to plasma level of D-vitamin at inclusion to the study.
Sub analysis of all primary and secondary outcome measures will be performed according to this criteria.
Time frame: From randomisation until 12 months after cessation of ATD treatment, an expected average of 24 months
Proportion of participants without relapse within the first year after cessation of ATD treatment according to baseline use of D-vitamin.
Sub analysis of baseline "users" versus "non-users" of D-vitamin supplementation with regards to effects of intervention on all primary and secondary outcome measures.
Time frame: From randomisation until 12 months after cessation of ATD treatment, an expected average of 24 months
Quality of Life as measured by Health questionnaires
Thyroid specific QoL as measured by the global score in the thyPRO questionnaire. Hyperthyroid symptoms (thyPRO subscale) Proportion of patients with eye symptoms (thyPRO subscale)
Time frame: 6 weeks
Quality of Life as measured by Health questionnaires
Thyroid specific QoL as measured by the global score in the thyPRO questionnaire. Hyperthyroid symptoms (thyPRO subscale) Proportion of patients with eye symptoms (thyPRO subscale)
Time frame: 3 months
Quality of Life as measured by Health questionnaires
Thyroid specific QoL as measured by the global score in the thyPRO questionnaire. Hyperthyroid symptoms (thyPRO subscale) Proportion of patients with eye symptoms (thyPRO subscale)
Time frame: 6 months
Quality of Life as measured by Health questionnaires
Thyroid specific QoL as measured by the global score in the thyPRO questionnaire. Hyperthyroid symptoms (thyPRO subscale) Proportion of patients with eye symptoms (thyPRO subscale)
Time frame: 9 months
Quality of Life as measured by Health questionnaires
Thyroid specific QoL as measured by the global score in the thyPRO questionnaire. Hyperthyroid symptoms (thyPRO subscale) Proportion of patients with eye symptoms (thyPRO subscale)
Time frame: 12 months
Quality of Life as measured by Health questionnaires
Thyroid specific QoL as measured by the global score in the thyPRO questionnaire. Hyperthyroid symptoms (thyPRO subscale) Proportion of patients with eye symptoms (thyPRO subscale)
Time frame: 18 months
Quality of Life as measured by Health questionnaires
Thyroid specific QoL as measured by the global score in the thyPRO questionnaire. Hyperthyroid symptoms (thyPRO subscale) Proportion of patients with eye symptoms (thyPRO subscale)
Time frame: 24 months
Biomarkers of calcium- and bone metabolism.
Effects of intervention on biochemical markers of calcium and bone metabolism, such as calcium, phosphate, parathyroid hormone, calcitriol, vitamin D-binding protein, bone-specific alkaline phosphatase, osteocalcin, and N-terminal propeptide of type 1 procollagen (P1NP). Also C-terminal telopeptide of type 1 collagen (CTX) and N-telopeptide of type 1 collagen (NTX) among others.
Time frame: 3 months, 9 months and 12 months after cessation of ATD treatment, an expected average of 24 months
Level of Thyrotropin receptor antibody (TRAb)
Level of TRAb at 3 and 9 months and at end of study period (maximum of 36 months)
Time frame: 3 months, 9 months and 12 months after cessation of ATD treatment, an expected average of 24 months
Level of 25 hydroxy vitamin D
Level of 25 hydroxy vitamin D at 3 and 9 months and at end of study period (maximum of 36 months)
Time frame: From randomisation until 12 months after cessation of ATD treatment, an expected average of 24 months