NCT02384668

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
278

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Mar 2015

Longer than P75 for not_applicable

Geographic Reach
1 country

8 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 9, 2015

Completed
2 months until next milestone

First Posted

Study publicly available on registry

March 10, 2015

Completed
14 days until next milestone

Study Start

First participant enrolled

March 24, 2015

Completed
5.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2020

Completed
Last Updated

September 1, 2022

Status Verified

August 1, 2022

Enrollment Period

5.7 years

First QC Date

January 9, 2015

Last Update Submit

August 26, 2022

Conditions

Graves' Disease

Keywords

CholecalciferolVitamin D3Arterial stiffnessQuality of LifeBone density and geometryMuscle strength and balance

Outcome Measures

Primary Outcomes (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.

    0-12 months after cessation of ATD treatment

Secondary Outcomes (16)

  • 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 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 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 fails to stop ATD treatment within 24 months after initiation of ATD therapy.

    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.

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

  • +11 more secondary outcomes

Other Outcomes (12)

  • Immune response as measured by flow cytometric analysis of T- and B-cells

    First nine months.

  • Immune response as measured by soluble HLA-G (Human Leukocyte Antigen-G)

    First nine months.

  • Immune response as measured by membrane-bound HLA-G (Human Leukocyte Antigen-G)

    First nine months.

  • +9 more other outcomes

Study Arms (2)

Cholecalciferol

ACTIVE COMPARATOR

Cholecalciferol 70 mcg per day Other name: Vitamin D3.

Dietary Supplement: Cholecalciferol

Placebo

PLACEBO COMPARATOR

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.

Dietary Supplement: Placebo

Interventions

CholecalciferolDIETARY_SUPPLEMENT

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.

Also known as: Vitamin D3
Cholecalciferol
PlaceboDIETARY_SUPPLEMENT

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

Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • Previously diagnosed hyperthyroidism
  • 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
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

Department of Endocrinology and Internal Medicine, Aarhus University Hospital

Aarhus C, 8000, Denmark

Location

Gentofte Hospital

Gentofte Municipality, 2900, Denmark

Location

Department of Internal Medicine, Regionshospitalet Herning

Herning, 7400, Denmark

Location

Department of Internal Medicine, Regionshospitalet Holstebro

Holstebro, 7500, Denmark

Location

Department of Internal Medicine, Regionshospitalet Horsens

Horsens, 8700, Denmark

Location

Department of Internal Medicine, Regionhospitalet Randers

Randers, 8930, Denmark

Location

Department of Internal Medicine, Diagnostisk Center, Regionshospitalet Silkeborg

Silkeborg, 8600, Denmark

Location

Department of Internal Medicine, Regionshospitalet Viborg

Viborg, 8800, Denmark

Location

Related Publications (5)

  • 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.

    PMID: 39264438DERIVED

  • 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.

    PMID: 37218433DERIVED

  • 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.

    PMID: 35018442DERIVED

  • 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.

    PMID: 31910101DERIVED

  • 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.

    PMID: 31280470DERIVED

MeSH Terms

Conditions

Graves Disease

Interventions

Cholecalciferol

Condition Hierarchy (Ancestors)

ExophthalmosOrbital DiseasesEye DiseasesGoiterThyroid DiseasesEndocrine System DiseasesHyperthyroidismAutoimmune DiseasesImmune System Diseases

Intervention Hierarchy (Ancestors)

CholestenesCholestanesSteroidsFused-Ring CompoundsPolycyclic CompoundsSterolsVitamin DSecosteroidsMembrane LipidsLipids

Study Officials

  • Lars Rejnmark, Professor

    Aarhus University Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 9, 2015

First Posted

March 10, 2015

Study Start

March 24, 2015

Primary Completion

December 1, 2020

Study Completion

December 1, 2020

Last Updated

September 1, 2022

Record last verified: 2022-08

Locations

DK(8)