D-vitamin And Graves' Disease; Morbidity And Relapse Reduction

Not Applicable

Completed

• Conditions: Graves' Disease
• Interventions: Dietary Supplement: Placebo; Dietary Supplement: Cholecalciferol

• Registration Number: NCT02384668
• Lead Sponsor: University of Aarhus

Brief Summary

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.

Detailed Description

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 Timeline

• Study First Submitted: 2015-01-09
• Study First Submitted QC: 2015-03-04
• Study First Posted: 2015-03-10
• Study Start: 2015-03-24
• Primary Completion: 2020-12
• Study Completion: 2020-12
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-26
• Last Update Posted: 2022-09-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 278

Inclusion Criteria

• A first time diagnosis of Graves' hyperthyroidism within the last three months, confirmed by TSH below 0.01 IU/L, and T3 or T4 levels above the reference interval necessitating ATD therapy
• Positive TRAb
• Speak and read Danish
• Written informed consent

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Exclusion Criteria

• Previously diagnosed hyperthyroidism
• ATD treatment initiated more than 3 months prior to inclusion
• Planned ablative therapy (radioactive iodine or thyroid surgery)
• Intake of more than 10 µg D-vitamin/day that the participant wishes to continue.
• Chronic granulomatous illness
• Persistent hypercalcemia (plasma calcium > 1.40 mmol/L)
• Reduced kidney function (eGFR < 45 ml/min)
• Treatment with immunomodulatory drugs
• Active malignant disease
• Alcohol or drug abuse
• Pregnancy at inclusion
• Major comorbidity, making the participant unlikely to continuously receive trial intervention.
• Allergy towards the components in the D-vitamin or the placebo pills.
• Unable to read and understand Danish
• Lack of informed consent.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo tablets are identical in regards to size and appearance to the experimental intervention tablet. The placebo regimen is identical to the vitamin D3 regimen.
Cholecalciferol	Cholecalciferol	Cholecalciferol 70 mcg per day Other name: Vitamin D3.

Primary Outcome Measures

Name	Time	Method
Proportion of participants without relapse within the first year after cessation of ATD treatment.	0-12 months 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.

Secondary Outcome Measures

Name	Time	Method
Effects of D-vitamin supplementation according to plasma level of D-vitamin at inclusion to the study.	From randomisation until 12 months after cessation of ATD treatment, an expected average of 24 months	Sub analysis of all primary and secondary outcome measures will be performed according to this criteria.
Quality of Life as measured by Health questionnaires	24 months	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)
The proportion of participants who has been referred to radioactive iodine or thyroid surgery at any time during the entire intervention period.	From randomisation until 12 months after cessation of ATD treatment, an expected average of 24 months	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 have relapse of hyperthyroidism (TSH<0.1) after cessation of ATD therapy	0-12 months after cessation of ATD treatment	The proportion of participants who have relapse of hyperthyroidism (TSH\<0.1) after cessation of ATD therapy
Level of 25 hydroxy vitamin D	From randomisation until 12 months after cessation of ATD treatment, an expected average of 24 months	Level of 25 hydroxy vitamin D at 3 and 9 months and at end of study period (maximum of 36 months)
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.	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 fails to stop ATD treatment within 24 months after initiation of ATD therapy.	0-24 months after initiation of ATD therapy	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
Proportion of participants without relapse within the first year after cessation of ATD treatment according to baseline use of D-vitamin.	From randomisation until 12 months after cessation of ATD treatment, an expected average of 24 months	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.
Biomarkers of calcium- and bone metabolism.	3 months, 9 months and 12 months after cessation of ATD treatment, an expected average of 24 months	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.
Level of Thyrotropin receptor antibody (TRAb)	3 months, 9 months and 12 months after cessation of ATD treatment, an expected average of 24 months	Level of TRAb at 3 and 9 months and at end of study period (maximum of 36 months)

Trial Locations

Locations (8)

Gentofte Hospital; 🇩🇰 Gentofte, Denmark

Department of Internal Medicine, Regionshospitalet Herning; 🇩🇰 Herning, Denmark

Department of Internal Medicine, Regionhospitalet Randers; 🇩🇰 Randers, Denmark

Department of Internal Medicine, Diagnostisk Center, Regionshospitalet Silkeborg; 🇩🇰 Silkeborg, Denmark

Department of Endocrinology and Internal Medicine, Aarhus University Hospital; 🇩🇰 Aarhus C, Denmark

Department of Internal Medicine, Regionshospitalet Holstebro; 🇩🇰 Holstebro, Denmark

Department of Internal Medicine, Regionshospitalet Horsens; 🇩🇰 Horsens, Denmark

Department of Internal Medicine, Regionshospitalet Viborg; 🇩🇰 Viborg, Denmark