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Graves' DiseaseDAGMARNCT02384668

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

A study testing Cholecalciferol in people with Graves' Disease, run by University of Aarhus at 8 sites in Denmark.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Graves' Disease
What is being tested?
Cholecalciferol
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
278 participants
Where
8 sitesDenmark
Study dates
24 Mar 2015to Dec 2020
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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)
Show all 15Show fewer
  • 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.

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

Denmark8 sites
  • Department of Endocrinology and Internal Medicine, Aarhus University Hospital

    Aarhus C, 8000

  • Gentofte Hospital

    Gentofte Municipality, 2900

  • Department of Internal Medicine, Regionshospitalet Herning

    Herning, 7400

  • Department of Internal Medicine, Regionshospitalet Holstebro

    Holstebro, 7500

  • Department of Internal Medicine, Regionshospitalet Horsens

    Horsens, 8700

  • Department of Internal Medicine, Regionhospitalet Randers

    Randers, 8930

  • Department of Internal Medicine, Diagnostisk Center, Regionshospitalet Silkeborg

    Silkeborg, 8600

  • Department of Internal Medicine, Regionshospitalet Viborg

    Viborg, 8800

Other trials in Denmark

About this study

Official title: The DAGMAR Study. D-vitamin And Graves' Disease; Morbidity And Relapse Reduction: A Randomised, Clinical Trial.

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.

Read the 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.

Conditions
Graves' Disease
Being tested
Cholecalciferol, Placebo
Keywords
Cholecalciferol, Vitamin D3, Arterial stiffness, Quality of Life, Bone density and geometry, Muscle strength and balance
Medical subject headings
Graves Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CholecalciferolDietary supplement

    Also called Vitamin D3

    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.

  • PlaceboDietary supplement

    One tablet per day. Placebo tablet identical in appearance to cholecalciferol tablet. Duration and cessation of treatment identical to intervention with cholecalciferol.

Study groups in NCT02384668
Study groupRoleWhat they receive
CholecalciferolActive comparatorCholecalciferol 70 mcg per day Other name: Vitamin D3.
Receives: Dietary Supplement: Cholecalciferol
PlaceboPlacebo comparatorPlacebo tablets are identical in regards to size and appearance to the experimental intervention tablet. The placebo regimen is identical to the vitamin D3 regimen.
Receives: Dietary Supplement: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 0-12 months after cessation of ATD treatment

Secondary outcomes (16)
  1. 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.

    Measured: From randomisation until 12 months after cessation of ATD treatment, an expected average of 24 months

  2. 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

    Measured: 0-12 months after cessation of ATD treatment

  3. 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.

    Measured: 0-12 months after cessation of ATD treatment

  4. The proportion of participants who fails to stop ATD treatment within 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

    Measured: 0-24 months after initiation of ATD therapy

  5. 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.

    Measured: From randomisation until 12 months after cessation of ATD treatment, an expected average of 24 months

  6. 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.

    Measured: From randomisation until 12 months after cessation of ATD treatment, an expected average of 24 months

  7. 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)

    Measured: 6 weeks

  8. 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)

    Measured: 3 months

  9. 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)

    Measured: 6 months

  10. 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)

    Measured: 9 months

  11. 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)

    Measured: 12 months

  12. 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)

    Measured: 18 months

  13. 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)

    Measured: 24 months

  14. 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.

    Measured: 3 months, 9 months and 12 months after cessation of ATD treatment, an expected average of 24 months

  15. Level of Thyrotropin receptor antibody (TRAb)

    Level of TRAb at 3 and 9 months and at end of study period (maximum of 36 months)

    Measured: 3 months, 9 months and 12 months after cessation of ATD treatment, an expected average of 24 months

  16. 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)

    Measured: From randomisation until 12 months after cessation of ATD treatment, an expected average of 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Mar 2015 (estimated)
  2. Study start24 Mar 2015
  3. Primary completionDec 2020
  4. Study completionDec 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
278 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02384668
Sponsor's protocol ID
12122012
Acronym
DAGMAR
Status last verified
Aug 2022
First submitted
9 Jan 2015
Last updated
1 Sep 2022
Results posted
No
Data monitoring committee
No

Publications

  • Grove-Laugesen D, Ebbehoj E, Watt T, Hansen KW, Rejnmark L. Changes in bone density and microarchitecture following treatment of Graves' disease and the effects of vitamin D supplementation. A randomized clinical trial. Osteoporos Int. 2024 Dec;35(12):2153-2164. doi: 10.1007/s00198-024-07241-y. Epub 2024 Sep 12.

    PubMed 39264438
  • Grove-Laugesen D, Ebbehoj E, Watt T, Riis AL, Ostergard T, Bruun BJ, Juel Christiansen J, Hansen KW, Rejnmark L. Effect of Vitamin D Supplementation on Graves' Disease: The DAGMAR Trial. Thyroid. 2023 Sep;33(9):1110-1118. doi: 10.1089/thy.2023.0111. Epub 2023 Jun 26.

    PubMed 37218433
  • Bislev LS, Wamberg L, Rolighed L, Grove-Laugesen D, Rejnmark L. Effect of Daily Vitamin D3 Supplementation on Muscle Health: An Individual Participant Meta-analysis. J Clin Endocrinol Metab. 2022 Apr 19;107(5):1317-1327. doi: 10.1210/clinem/dgac004.

    PubMed 35018442
  • Grove-Laugesen D, Cramon PK, Malmstroem S, Ebbehoj E, Watt T, Hansen KW, Rejnmark L. Effects of Supplemental Vitamin D on Muscle Performance and Quality of Life in Graves' Disease: A Randomized Clinical Trial. Thyroid. 2020 May;30(5):661-671. doi: 10.1089/thy.2019.0634. Epub 2020 Feb 7.

    PubMed 31910101
  • Grove-Laugesen D, Malmstroem S, Ebbehoj E, Riis AL, Watt T, Hansen KW, Rejnmark L. Effect of 9 months of vitamin D supplementation on arterial stiffness and blood pressure in Graves' disease: a randomized clinical trial. Endocrine. 2019 Nov;66(2):386-397. doi: 10.1007/s12020-019-01997-8. Epub 2019 Jul 6.

    PubMed 31280470

Questions about this trial

What is this clinical trial studying?

A study testing Cholecalciferol in people with Graves' Disease, run by University of Aarhus at 8 sites in Denmark.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of participants without relapse within the first year after cessation of ATD treatment. (time frame: 0-12 months after cessation of ATD treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02384668, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2022.

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