Ignite Creation Date:
2025-12-24 @ 5:32 PM
Ignite Modification Date:
2026-02-22 @ 9:32 AM
Study NCT ID:
NCT02384668
Status:
COMPLETED
Last Update Posted:
2022-09-01
First Post:
2015-01-09
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
D-vitamin And Graves' Disease; Morbidity And Relapse Reduction
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D006111', 'term': 'Graves Disease'}], 'ancestors': [{'id': 'D005094', 'term': 'Exophthalmos'}, {'id': 'D009916', 'term': 'Orbital Diseases'}, {'id': 'D005128', 'term': 'Eye Diseases'}, {'id': 'D006042', 'term': 'Goiter'}, {'id': 'D013959', 'term': 'Thyroid Diseases'}, {'id': 'D004700', 'term': 'Endocrine System Diseases'}, {'id': 'D006980', 'term': 'Hyperthyroidism'}, {'id': 'D001327', 'term': 'Autoimmune Diseases'}, {'id': 'D007154', 'term': 'Immune System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D002762', 'term': 'Cholecalciferol'}], 'ancestors': [{'id': 'D002782', 'term': 'Cholestenes'}, {'id': 'D002776', 'term': 'Cholestanes'}, {'id': 'D013256', 'term': 'Steroids'}, {'id': 'D000072473', 'term': 'Fused-Ring Compounds'}, {'id': 'D011083', 'term': 'Polycyclic Compounds'}, {'id': 'D013261', 'term': 'Sterols'}, {'id': 'D014807', 'term': 'Vitamin D'}, {'id': 'D012632', 'term': 'Secosteroids'}, {'id': 'D008563', 'term': 'Membrane Lipids'}, {'id': 'D008055', 'term': 'Lipids'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2017-05-11', 'size': 393821, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_000.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2022-08-21T16:50', 'hasProtocol': True}, {'date': '2013-01-25', 'size': 809465, 'label': 'Informed Consent Form', 'hasIcf': True, 'hasSap': False, 'filename': 'ICF_001.pdf', 'typeAbbrev': 'ICF', 'uploadDate': '2022-08-25T05:57', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 278}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2015-03-24', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2022-08', 'completionDateStruct': {'date': '2020-12', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2022-08-26', 'studyFirstSubmitDate': '2015-01-09', 'studyFirstSubmitQcDate': '2015-03-04', 'lastUpdatePostDateStruct': {'date': '2022-09-01', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2015-03-10', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2020-12', 'type': 'ACTUAL'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Immune response as measured by flow cytometric analysis of T- and B-cells', 'timeFrame': 'First nine months.', 'description': 'In a subcohort of 50 participants blood samples will be investigated by flow cytometry. Lymphocyte subpopulations will be quantified.'}, {'measure': 'Immune response as measured by soluble HLA-G (Human Leukocyte Antigen-G)', 'timeFrame': 'First nine months.', 'description': 'In a subcohort of 50 participants soluble HLA-G (Human Leukocyte Antigen-G) will be quantified based on blood samples.'}, {'measure': 'Immune response as measured by membrane-bound HLA-G (Human Leukocyte Antigen-G)', 'timeFrame': 'First nine months.', 'description': 'In a subcohort of 50 participants membrane-bound HLA-G (Human Leukocyte Antigen-G) will be quantified based on expression on monocytes.'}, {'measure': 'Immune response assessed by qualitative analysis of regulatory T lymphocytes', 'timeFrame': 'First nine months.', 'description': 'In a subcohort of 50 participants functional analysis of the suppressive capacity of regulatory T lymphocytes will be measured at 3 and 9 months after randomisation.'}, {'measure': 'Arterial stiffness as measured by tonometry', 'timeFrame': 'First nine months', 'description': 'Indices of arterial stiffness at 3 and 9 months after randomisation in a subcohort of 80 participants'}, {'measure': 'Muscle strength and balance as measured by isometric tests and dynamic stability tests.', 'timeFrame': 'First nine months', 'description': 'Effects on muscle strength (isometric tests of flexion and extension of thigh and hand), two function-tests (timed up-and go and timed stand-and-sit), and postural stability at 3 and 9 months after randomisation in a subcohort of 80 participants'}, {'measure': 'Bone density and geometry as measured by DXA and HRpQCT scans', 'timeFrame': 'First nine months', 'description': 'Bone density, geometry, and quality as assessed by dual energy x-ray absorptiometry (DXA) and high resolution peripheral quantitative computed tomography (HRpQCT)-scans 9 months months after randomisation in a subcohort of 80 participants'}, {'measure': 'Effect on thyroid gland size by ultrasound examination', 'timeFrame': 'First nine months', 'description': 'Estimation of thyroid volume by ultrasound examination'}, {'measure': 'Proportion of patients with adverse reactions to anti thyroid drugs', 'timeFrame': 'From randomisation until 12 months after cessation of ATD treatment, an expected average of 24 months', 'description': 'Proportion of patients with adverse reactions to anti thyroid drugs measured by regular questionnaires and reported complaints and events in patient journals'}, {'measure': 'Proportion of patients with serious adverse events', 'timeFrame': 'From randomisation until 12 months after cessation of ATD treatment, an expected average of 24 months', 'description': 'Based on reports from patients journals and hospitals admissions of agranulocytosis, leukopenia, aplastic anemia, hepatitis, and vasculitis'}, {'measure': 'Effects on frequency of infectious disease as measured by use of antibiotics', 'timeFrame': 'From randomisation until 12 months after cessation of ATD treatment, an expected average of 24 months', 'description': 'Data from the Danish prescription database'}, {'measure': 'Effects on use of Health care services as measured by hospital admissions and visits to general practitioner', 'timeFrame': 'From randomisation until 12 months after cessation of ATD treatment, an expected average of 24 months', 'description': 'Measured by all cause-hospital admissions and visits to general practitioner'}], 'primaryOutcomes': [{'measure': 'Proportion of participants without relapse within the first year after cessation of ATD treatment.', 'timeFrame': '0-12 months after cessation of ATD treatment', 'description': 'A relapse is defined as:\n\nThe 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.'}], 'secondaryOutcomes': [{'measure': 'The proportion of participants who has been referred to radioactive iodine or thyroid surgery at any time during the entire intervention period.', 'timeFrame': 'From randomisation until 12 months after cessation of ATD treatment, an expected average of 24 months', 'description': 'The proportion of participants who has been referred to radioactive iodine or thyroid surgery at any time during the entire intervention period.'}, {'measure': 'The proportion of participants who have relapse of hyperthyroidism (TSH<0.1) after cessation of ATD therapy', 'timeFrame': '0-12 months after cessation of ATD treatment', 'description': 'The proportion of participants who have relapse of hyperthyroidism (TSH\\<0.1) after cessation of ATD therapy'}, {'measure': '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.', 'timeFrame': '0-12 months after cessation of ATD treatment', 'description': '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.'}, {'measure': 'The proportion of participants who fails to stop ATD treatment within 24 months after initiation of ATD therapy.', 'timeFrame': '0-24 months after initiation of ATD therapy', 'description': "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"}, {'measure': 'Effects of D-vitamin supplementation according to plasma level of D-vitamin at inclusion to the study.', 'timeFrame': 'From randomisation until 12 months after cessation of ATD treatment, an expected average of 24 months', 'description': 'Sub analysis of all primary and secondary outcome measures will be performed according to this criteria.'}, {'measure': 'Proportion of participants without relapse within the first year after cessation of ATD treatment according to baseline use of D-vitamin.', 'timeFrame': 'From randomisation until 12 months after cessation of ATD treatment, an expected average of 24 months', 'description': '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.'}, {'measure': 'Quality of Life as measured by Health questionnaires', 'timeFrame': '6 weeks', 'description': 'Thyroid specific QoL as measured by the global score in the thyPRO questionnaire.\n\nHyperthyroid symptoms (thyPRO subscale) Proportion of patients with eye symptoms (thyPRO subscale)'}, {'measure': 'Quality of Life as measured by Health questionnaires', 'timeFrame': '3 months', 'description': 'Thyroid specific QoL as measured by the global score in the thyPRO questionnaire.\n\nHyperthyroid symptoms (thyPRO subscale) Proportion of patients with eye symptoms (thyPRO subscale)'}, {'measure': 'Quality of Life as measured by Health questionnaires', 'timeFrame': '6 months', 'description': 'Thyroid specific QoL as measured by the global score in the thyPRO questionnaire.\n\nHyperthyroid symptoms (thyPRO subscale) Proportion of patients with eye symptoms (thyPRO subscale)'}, {'measure': 'Quality of Life as measured by Health questionnaires', 'timeFrame': '9 months', 'description': 'Thyroid specific QoL as measured by the global score in the thyPRO questionnaire.\n\nHyperthyroid symptoms (thyPRO subscale) Proportion of patients with eye symptoms (thyPRO subscale)'}, {'measure': 'Quality of Life as measured by Health questionnaires', 'timeFrame': '12 months', 'description': 'Thyroid specific QoL as measured by the global score in the thyPRO questionnaire.\n\nHyperthyroid symptoms (thyPRO subscale) Proportion of patients with eye symptoms (thyPRO subscale)'}, {'measure': 'Quality of Life as measured by Health questionnaires', 'timeFrame': '18 months', 'description': 'Thyroid specific QoL as measured by the global score in the thyPRO questionnaire.\n\nHyperthyroid symptoms (thyPRO subscale) Proportion of patients with eye symptoms (thyPRO subscale)'}, {'measure': 'Quality of Life as measured by Health questionnaires', 'timeFrame': '24 months', 'description': 'Thyroid specific QoL as measured by the global score in the thyPRO questionnaire.\n\nHyperthyroid symptoms (thyPRO subscale) Proportion of patients with eye symptoms (thyPRO subscale)'}, {'measure': 'Biomarkers of calcium- and bone metabolism.', 'timeFrame': '3 months, 9 months and 12 months after cessation of ATD treatment, an expected average of 24 months', 'description': '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.'}, {'measure': 'Level of Thyrotropin receptor antibody (TRAb)', 'timeFrame': '3 months, 9 months and 12 months after cessation of ATD treatment, an expected average of 24 months', 'description': 'Level of TRAb at 3 and 9 months and at end of study period (maximum of 36 months)'}, {'measure': 'Level of 25 hydroxy vitamin D', 'timeFrame': 'From randomisation until 12 months after cessation of ATD treatment, an expected average of 24 months', 'description': 'Level of 25 hydroxy vitamin D at 3 and 9 months and at end of study period (maximum of 36 months)'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Cholecalciferol', 'Vitamin D3', 'Arterial stiffness', 'Quality of Life', 'Bone density and geometry', 'Muscle strength and balance'], 'conditions': ["Graves' Disease"]}, 'referencesModule': {'references': [{'pmid': '39264438', 'type': 'DERIVED', 'citation': "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': '37218433', 'type': 'DERIVED', 'citation': "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': '35018442', 'type': 'DERIVED', 'citation': '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': '31910101', 'type': 'DERIVED', 'citation': "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': '31280470', 'type': 'DERIVED', 'citation': "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."}]}, 'descriptionModule': {'briefSummary': "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.", 'detailedDescription': "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."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* 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\n* Positive TRAb\n* Speak and read Danish\n* Written informed consent\n\nExclusion Criteria:\n\n* Previously diagnosed hyperthyroidism\n* ATD treatment initiated more than 3 months prior to inclusion\n* Planned ablative therapy (radioactive iodine or thyroid surgery)\n* Intake of more than 10 µg D-vitamin/day that the participant wishes to continue.\n* Chronic granulomatous illness\n* Persistent hypercalcemia (plasma calcium \\> 1.40 mmol/L)\n* Reduced kidney function (eGFR \\< 45 ml/min)\n* Treatment with immunomodulatory drugs\n* Active malignant disease\n* Alcohol or drug abuse\n* Pregnancy at inclusion\n* Major comorbidity, making the participant unlikely to continuously receive trial intervention.\n* Allergy towards the components in the D-vitamin or the placebo pills.\n* Unable to read and understand Danish\n* Lack of informed consent."}, 'identificationModule': {'nctId': 'NCT02384668', 'acronym': 'DAGMAR', 'briefTitle': "D-vitamin And Graves' Disease; Morbidity And Relapse Reduction", 'organization': {'class': 'OTHER', 'fullName': 'University of Aarhus'}, 'officialTitle': "The DAGMAR Study. D-vitamin And Graves' Disease; Morbidity And Relapse Reduction: A Randomised, Clinical Trial.", 'orgStudyIdInfo': {'id': '12122012'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Cholecalciferol', 'description': 'Cholecalciferol 70 mcg per day Other name: Vitamin D3.', 'interventionNames': ['Dietary Supplement: Cholecalciferol']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'description': 'Placebo tablets are identical in regards to size and appearance to the experimental intervention tablet.\n\nThe placebo regimen is identical to the vitamin D3 regimen.', 'interventionNames': ['Dietary Supplement: Placebo']}], 'interventions': [{'name': 'Cholecalciferol', 'type': 'DIETARY_SUPPLEMENT', 'otherNames': ['Vitamin D3'], 'description': "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.", 'armGroupLabels': ['Cholecalciferol']}, {'name': 'Placebo', 'type': 'DIETARY_SUPPLEMENT', 'description': 'One tablet per day. Placebo tablet identical in appearance to cholecalciferol tablet. Duration and cessation of treatment identical to intervention with cholecalciferol.', 'armGroupLabels': ['Placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '8000', 'city': 'Aarhus C', 'country': 'Denmark', 'facility': 'Department of Endocrinology and Internal Medicine, Aarhus University Hospital', 'geoPoint': {'lat': 56.16558, 'lon': 10.21231}}, {'zip': '2900', 'city': 'Gentofte Municipality', 'country': 'Denmark', 'facility': 'Gentofte Hospital', 'geoPoint': {'lat': 55.74903, 'lon': 12.54601}}, {'zip': '7400', 'city': 'Herning', 'country': 'Denmark', 'facility': 'Department of Internal Medicine, Regionshospitalet Herning', 'geoPoint': {'lat': 56.13615, 'lon': 8.97662}}, {'zip': '7500', 'city': 'Holstebro', 'country': 'Denmark', 'facility': 'Department of Internal Medicine, Regionshospitalet Holstebro', 'geoPoint': {'lat': 56.36009, 'lon': 8.61607}}, {'zip': '8700', 'city': 'Horsens', 'country': 'Denmark', 'facility': 'Department of Internal Medicine, Regionshospitalet Horsens', 'geoPoint': {'lat': 55.86066, 'lon': 9.85034}}, {'zip': '8930', 'city': 'Randers', 'country': 'Denmark', 'facility': 'Department of Internal Medicine, Regionhospitalet Randers', 'geoPoint': {'lat': 56.4607, 'lon': 10.03639}}, {'zip': '8600', 'city': 'Silkeborg', 'country': 'Denmark', 'facility': 'Department of Internal Medicine, Diagnostisk Center, Regionshospitalet Silkeborg', 'geoPoint': {'lat': 56.1697, 'lon': 9.54508}}, {'zip': '8800', 'city': 'Viborg', 'country': 'Denmark', 'facility': 'Department of Internal Medicine, Regionshospitalet Viborg', 'geoPoint': {'lat': 56.45319, 'lon': 9.40201}}], 'overallOfficials': [{'name': 'Lars Rejnmark, Professor', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Aarhus University Hospital'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Aarhus', 'class': 'OTHER'}, 'collaborators': [{'name': 'Aarhus University Hospital', 'class': 'OTHER'}, {'name': 'Regionshospitalet Silkeborg', 'class': 'OTHER'}, {'name': 'Regional Hospital Holstebro', 'class': 'OTHER'}, {'name': 'Regionshospitalet Horsens', 'class': 'OTHER'}, {'name': 'Randers Regional Hospital', 'class': 'OTHER'}, {'name': 'Regionshospitalet Viborg, Skive', 'class': 'OTHER'}, {'name': 'Herning Hospital', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR'}}}}