Ignite Creation Date:
2026-03-26 @ 3:17 PM
Ignite Modification Date:
2026-03-30 @ 10:28 PM
Study NCT ID:
NCT07416656
Status:
NOT_YET_RECRUITING
Last Update Posted:
2026-02-18
First Post:
2026-02-10
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Validation of Hemoglobin A1c in Patients With Inflammatory Arthritis Treated With Sulfasalazine
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2026-03-25'}, 'conditionBrowseModule': {'meshes': [{'id': 'D001168', 'term': 'Arthritis'}, {'id': 'D003920', 'term': 'Diabetes Mellitus'}, {'id': 'D001172', 'term': 'Arthritis, Rheumatoid'}, {'id': 'D003922', 'term': 'Diabetes Mellitus, Type 1'}, {'id': 'D003924', 'term': 'Diabetes Mellitus, Type 2'}], 'ancestors': [{'id': 'D007592', 'term': 'Joint Diseases'}, {'id': 'D009140', 'term': 'Musculoskeletal Diseases'}, {'id': 'D044882', 'term': 'Glucose Metabolism Disorders'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D004700', 'term': 'Endocrine System Diseases'}, {'id': 'D012216', 'term': 'Rheumatic Diseases'}, {'id': 'D003240', 'term': 'Connective Tissue Diseases'}, {'id': 'D017437', 'term': 'Skin and Connective Tissue Diseases'}, {'id': 'D001327', 'term': 'Autoimmune Diseases'}, {'id': 'D007154', 'term': 'Immune System Diseases'}]}}, 'protocolSection': {'designModule': {'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 75}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2026-02', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2026-02', 'completionDateStruct': {'date': '2026-09', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2026-02-10', 'studyFirstSubmitDate': '2026-02-10', 'studyFirstSubmitQcDate': '2026-02-10', 'lastUpdatePostDateStruct': {'date': '2026-02-18', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2026-02-18', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2026-06', 'type': 'ESTIMATED'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Feasibility of automated laboratory-based HbA1c alert in sulfasalazine-treated patients', 'timeFrame': 'Approximately 9 months', 'description': 'This outcome assesses the feasibility of implementing an automated laboratory-based alert in the laboratory information system (LABKA) to flag potential interpretive limitations of HbA1c in patients treated with sulfasalazine. Feasibility is evaluated by determining whether HbA1c test results can be systematically linked to active sulfasalazine treatment and whether an automated notification can be generated to inform clinicians that HbA1c may underestimate true glycaemic status in this context.'}], 'primaryOutcomes': [{'measure': 'Prevalence of undiagnosed diabetes mellitus', 'timeFrame': 'Within 14-21 days', 'description': 'The primary outcome is the prevalence of previously undiagnosed diabetes mellitus among adults with inflammatory arthritis treated with sulfasalazine who do not have a known diagnosis of diabetes and have a borderline HbA1c value. Undiagnosed diabetes is defined based on fasting plasma glucose measurements obtained during the study, in accordance with established diagnostic criteria. The prevalence is expressed as the proportion of participants meeting the diagnostic criteria for diabetes mellitus.'}], 'secondaryOutcomes': [{'measure': 'Agreement between HbA1c and CGM-derived mean glucose in sulfasalazine-treated patients', 'timeFrame': 'Within 14-21 days', 'description': 'The secondary outcome is the agreement between HbA1c and average glucose levels measured by blinded CGM in adults with inflammatory arthritis treated with sulfasalazine. Mean glucose derived from CGM over the monitoring period is compared with contemporaneous HbA1c values to evaluate whether HbA1c accurately reflects true glycaemic status in this population. The analysis includes participants with known diabetes mellitus and participants without known diabetes but with borderline HbA1c values.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Validation of HbA1c', 'Sulfasalazine', 'Salazopyrin', 'Continuous glucose monitoring', 'CGM', 'Type 2 Diabetes', 'Diabetes', 'Hemoglobin A1c', 'HbA1c', 'Type 1 Diabetes', 'Fasting blood glucose'], 'conditions': ['Inflammatory Arthritis', 'Diabetes (DM)', 'Rheumatoid Arthritis (RA)', 'Type 1 Diabetes Mellitus', 'Type 2 Diabetes (T2DM)']}, 'referencesModule': {'references': [{'pmid': '35629988', 'type': 'RESULT', 'citation': 'Infante M, Padilla N, Alejandro R, Caprio M, Della-Morte D, Fabbri A, Ricordi C. Diabetes-Modifying Antirheumatic Drugs: The Roles of DMARDs as Glucose-Lowering Agents. Medicina (Kaunas). 2022 Apr 21;58(5):571. doi: 10.3390/medicina58050571.'}, {'type': 'RESULT', 'citation': 'Farmacies sales of drugs. eSundhed.dk [Internet]. Available from: https://www.esundhed.dk/Emner/Laegemidler/Apotekernes-salg-af-laegemidler'}, {'pmid': '21389043', 'type': 'RESULT', 'citation': 'Lindhardsen J, Ahlehoff O, Gislason GH, Madsen OR, Olesen JB, Torp-Pedersen C, Hansen PR. The risk of myocardial infarction in rheumatoid arthritis and diabetes mellitus: a Danish nationwide cohort study. Ann Rheum Dis. 2011 Jun;70(6):929-34. doi: 10.1136/ard.2010.143396. Epub 2011 Mar 9.'}, {'pmid': '25689371', 'type': 'RESULT', 'citation': 'Baghdadi LR, Woodman RJ, Shanahan EM, Mangoni AA. The impact of traditional cardiovascular risk factors on cardiovascular outcomes in patients with rheumatoid arthritis: a systematic review and meta-analysis. PLoS One. 2015 Feb 17;10(2):e0117952. doi: 10.1371/journal.pone.0117952. eCollection 2015.'}, {'pmid': '33236391', 'type': 'RESULT', 'citation': "N'Dow SMS, Donnelly LA, Pearson ER, Rena G. In a cohort of individuals with type 2 diabetes using the drug sulfasalazine, HbA1c lowering is associated with haematological changes. Diabet Med. 2021 Sep;38(9):e14463. doi: 10.1111/dme.14463. Epub 2020 Dec 8."}, {'pmid': '29382985', 'type': 'RESULT', 'citation': 'Mitchell K, Mukhopadhyay B. Drug-Induced Falsely Low A1C: Report of a Case Series From a Diabetes Clinic. Clin Diabetes. 2018 Jan;36(1):80-84. doi: 10.2337/cd17-0005. No abstract available.'}, {'pmid': '8799639', 'type': 'RESULT', 'citation': 'Tack CJ, Wetzels JF. Decreased HbA1c levels due to sulfonamide-induced hemolysis in two IDDM patients. Diabetes Care. 1996 Jul;19(7):775-6. doi: 10.2337/diacare.19.7.775.'}, {'type': 'RESULT', 'citation': 'Danish Society of Rheumatology. Rheumatoid arthritis - national clinical guideline [Internet]. [cited 2025 Aug 20].'}, {'type': 'RESULT', 'citation': 'Danish Society of Rheumatology. Sulfasalazine [Internet]. [cited 2025 Aug 20]. Available from: https://danskreumatologi.dk/laegemidler/sulfasalazin/'}, {'type': 'RESULT', 'citation': 'Christensen SH HN, Janukonyté J, Vestergaard EM, Samson M.. . Brug af glykeret hæmoglobin-måling i praksis. . Ugeskr Læger.183(V12200902):1-8.'}, {'pmid': '34611711', 'type': 'RESULT', 'citation': 'Pant V. HbA1c Below the Reportable Range. Lab Med. 2022 Mar 7;53(2):e44-e47. doi: 10.1093/labmed/lmab082.'}]}, 'descriptionModule': {'briefSummary': 'The purpose of this study is to examine whether the blood test Hemoglobin A1c (HbA1c) gives an accurate picture of blood glucose levels in patients with inflammatory arthritis who are treated with sulfasalazine. HbA1c is widely used to diagnose and monitor diabetes, but sulfasalazine can shorten red blood cell lifespan and thereby lower HbA1c values independently of actual glucose levels.\n\nThis may lead to underdiagnosis of diabetes in patients who develop diabetes during sulfasalazine treatment, and to undertreatment in patients with known diabetes due to falsely reassuring HbA1c values.\n\nThe study aims to answer two main questions:\n\n1. How many patients treated with sulfasalazine have undiagnosed diabetes despite having HbA1c values below the diagnostic threshold?\n2. Does HbA1c underestimate actual glucose levels when compared with continuous glucose monitoring (CGM) in patients with sulfasalazine-treated inflammatory arthritis, both in those with known diabetes and those that are not diagnosed with diabetes but have borderline HbA1c values (≥ 38 mmol/mol)?', 'detailedDescription': 'HbA1c is widely used to diagnose diabetes and to monitor long-term glycaemic control. HbA1c reflects average blood glucose levels over approximately two months but can be influenced by factors unrelated to glucose, including changes in red blood cell lifespan. Sulfasalazine, a disease-modifying antirheumatic drug commonly used to treat inflammatory arthritis, is known to cause mild haemolysis in some patients, which can lower HbA1c values independently of actual glucose levels.\n\nThis effect may have important clinical consequences. In patients without diabetes at the start of sulfasalazine treatment, HbA1c values may remain below diagnostic thresholds even if diabetes develops over time, potentially delaying diagnosis. In patients with established diabetes, sulfasalazine-associated lowering of HbA1c may give a misleading impression of adequate glycaemic control, which may result in insufficient treatment intensification despite elevated true glucose levels. Together, these mechanisms may contribute to underdiagnosis and undertreatment of diabetes in patients receiving sulfasalazine.\n\nCGM provides direct, sensor-based measurements of interstitial glucose levels and is not affected by red blood cell turnover. CGM therefore offers an opportunity to assess actual glycaemic exposure independently of HbA1c. However, prospective data comparing HbA1c with CGM-derived glucose measures in sulfasalazine-treated patients with inflammatory arthritis are lacking.\n\nThis study is a prospective observational investigation conducted in patients with inflammatory arthritis treated with sulfasalazine. Participants include both individuals with known diabetes and individuals without known diabetes who have HbA1c values in the borderline range. Each participant undergoes a single study phase in which blinded CGM is worn for up to 14 days, with blood sampling performed within the same time period. In participants without known diabetes, fasting plasma glucose measurements are used to evaluate the presence of previously unrecognised diabetes.\n\nBy comparing HbA1c values with CGM-derived average glucose levels, the study aims to evaluate whether HbA1c accurately reflects glycaemic status in sulfasalazine-treated patients. The results are expected to improve understanding of the limitations of HbA1c in this clinical context and to inform future strategies for diabetes diagnosis and monitoring in patients receiving sulfasalazine, including the potential need for alternative or supplementary glucose assessment methods.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'Patients will be recruited from the rheumatology outpatient clinic at the Medicial Diagnostic Center, Silkeborg Regional Hospital. Potential participants will be identified electronically using registry data. Scrutiny of their electronical medical records will be performed to confirm eligibility based on the above mentioned inclusion and exclusion criteria.', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Age ≥18 years\n* Treatment with sulfasalazine for at least 2 months prior to inclusion\n* Inflammatory arthritis diagnosis (Reumatoid Arthritis, Reaktive Arthritis, Axial spa, Psoriatic spondylitis, and Juvenil artrit)\n* HbA1c ≥38 mmol/mol obtained at least 2 months after sulfasalazine initiation OR a diabetes mellitus diagnosis (Type 1 diabetes mellitus, Type 2 diabetes mellitus, Malnutrition-related diabetes mellitus, Other specified diabetes mellitus (andre specificerede former for diabetes), and Unspecified diabetes mellitus (uspecificeret diabetes))\n* Can communicate in Danish\n* Informed consent including permission to upload glucose data and study ID to the Libreview Platform.\n\nExclusion Criteria:\n\n* Systemic treatment or local injections with glucocorticoids within the previous 2 months or planned within the following 4 weeks\n* Clinical conditions interfering with the interpretation of HbA1c expect for sulfasalazine alterations in red cell lifespan (etc. Dapson treatment)\n* Allergy towards the adhesive used in the CGM\n* Considered ineligible for participating (e.g. patients without decision-making capacity, , malignancy, terminal illness, ect.)'}, 'identificationModule': {'nctId': 'NCT07416656', 'acronym': 'DIA2SULFA', 'briefTitle': 'Validation of Hemoglobin A1c in Patients With Inflammatory Arthritis Treated With Sulfasalazine', 'organization': {'class': 'OTHER', 'fullName': 'Central Jutland Regional Hospital'}, 'officialTitle': 'How Can We Prevent the Underdiagnosis of Diabetes and the Undertreatment of Known Diabetes in Patients With Inflammatory Arthritis Treated With Sulfasalazine?', 'orgStudyIdInfo': {'id': '1-10-72-190-25'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'Inflammatory arthritis with borderline HbA1c', 'description': 'This cohort includes adults with inflammatory arthritis treated with sulfasalazine who do not have a prior diagnosis of diabetes mellitus and have a borderline HbA1c value (≥38 mmol/mol) measured at least two months after initiation of sulfasalazine.\n\nParticipants undergo blinded continuous glucose monitoring for up to 14 days to assess actual glucose levels. At the end of the monitoring period, blood samples are obtained for fasting plasma glucose and HbA1c.\n\nFasting plasma glucose and HbA1c are used to assess the presence of diabetes mellitus, and thereby whether HbA1c and is suitable for the diagnosis of diabetes in patients treated with sulfasalazine. Comparison of HbA1c with CGM-derived glucose measures allows evaluation of whether HbA1c accurately reflects true glycaemic status in patients treated with sulfasalazine.'}, {'label': 'Inflammatory arthritis with diabetes', 'description': 'This cohort includes adults with inflammatory arthritis and a known diagnosis of diabetes mellitus who are treated with sulfasalazine.\n\nParticipants undergo blinded continuous glucose monitoring for up to 14 days to assess average glucose levels. HbA1c is measured during the same period. Comparison of HbA1c with CGM-derived glucose measures allows evaluation of whether HbA1c accurately reflects glycaemic control in patients with established diabetes receiving sulfasalazine.'}]}, 'contactsLocationsModule': {'centralContacts': [{'name': 'Katrine B Gørlitz, MD', 'role': 'CONTACT', 'email': 'kagoer@rm.dk', 'phone': '0045 2421 0787'}], 'overallOfficials': [{'name': 'Klavs W Hansen, Clinical Professor', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Medicial Diagnostic Center, Silkeborg Regional Hospital'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Klavs Würgler Hansen', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR_INVESTIGATOR', 'investigatorTitle': 'Clinical Professor', 'investigatorFullName': 'Klavs Würgler Hansen', 'investigatorAffiliation': 'Central Jutland Regional Hospital'}}}}