Ignite Creation Date:
2025-12-24 @ 7:51 PM
Ignite Modification Date:
2025-12-28 @ 4:24 AM
Study NCT ID:
NCT04924504
Status:
UNKNOWN
Last Update Posted:
2022-11-23
First Post:
2021-06-07
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Mechanisms Behind Severe Insulin Resistance During Pregnancy in Women With Glucose Metabolic Disorders (SIR-MET)
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D003924', 'term': 'Diabetes Mellitus, Type 2'}, {'id': 'D016640', 'term': 'Diabetes, Gestational'}, {'id': 'D050177', 'term': 'Overweight'}, {'id': 'D009765', 'term': 'Obesity'}, {'id': 'D011254', 'term': 'Pregnancy in Diabetics'}, {'id': 'D007333', 'term': 'Insulin Resistance'}], 'ancestors': [{'id': 'D003920', 'term': 'Diabetes Mellitus'}, {'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': 'D011248', 'term': 'Pregnancy Complications'}, {'id': 'D005261', 'term': 'Female Urogenital Diseases and Pregnancy Complications'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D044343', 'term': 'Overnutrition'}, {'id': 'D009748', 'term': 'Nutrition Disorders'}, {'id': 'D001835', 'term': 'Body Weight'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D006946', 'term': 'Hyperinsulinism'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': 'Blood samples (maternal and umbilical) Placenta'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'CASE_CONTROL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 24}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'UNKNOWN', 'lastKnownStatus': 'RECRUITING', 'startDateStruct': {'date': '2021-05-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2022-11', 'completionDateStruct': {'date': '2023-12', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2022-11-22', 'studyFirstSubmitDate': '2021-06-07', 'studyFirstSubmitQcDate': '2021-06-07', 'lastUpdatePostDateStruct': {'date': '2022-11-23', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2021-06-14', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2023-12', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Association between insulin sensitivity Versus structural and functional changes in the placenta', 'timeFrame': 'Gestational week 28-36', 'description': 'Structural and functional changes in the placenta will be evaluated using a functional T2-weighted MRI scan. Specifically the function of placenta will be evaluated using a T2-value. Furthermore, structural and functional changes in the placenta will be evaluated through a postpartum histopathological examination of the placenta. Insulin sensitivity will be estimated using the homeostasis model assessment (HOMA-IR) based on fasting C-peptid and glucose concentrations.'}], 'secondaryOutcomes': [{'measure': 'Association between structural and functional changes in the placenta Versus fetal growth and development', 'timeFrame': 'Gestational week 28-36', 'description': 'Structural and functional changes in the placenta will be evaluated using a functional T2-weighted MRI scan. Specifically the function of placenta will be evaluated using a T2-value. Furthermore, structural and functional changes in the placenta will be evaluated through a postpartum histopathological examination of the placenta. Fetal growth will be evaluated through a fetal ultrasound measuring biometric parameters and bloodflow.'}, {'measure': 'Changes from baseline in serum or plasma concentration of metabolic, hormonal and inflammatory markers', 'timeFrame': 'Gestational week 28-36, at labour and 6 months postpartum', 'description': 'Serum concentration of IGF-1, IGFBP-3, IGFBP-1, FGF-21, Leptin, Adiponectin, CD163, Human Chorionic Gonadotropin, Progesterone, C-peptide, Cortisol, Prolactin, Sex Hormone Binding Globulin, Estradiol, Free fatty acids, Human Placental Lactogen, Human Placental Growth Hormone, PAPP-A, sFlt-1, PP13 and human anti-insulin antibody.\n\nPlasma concentrations of IL-6, IL-10, IL-1alpha, IFN-gamma, TNF-alpha, ICAM1, VCAM, LDL, HDL, Triglyceride, Gamma-Glutamyl Transferase, Thyrotropin, glucose and HbA1c.'}, {'measure': 'Assocation between the serum or plasma concentration of metabolic, hormonal and inflammatory markers Versus Insulin sensitivity', 'timeFrame': 'Gestational week 28-36, at labour and 6 months postpartum', 'description': 'Association between the metabolic, hormonal and inflammatory markers listed as Outcome 2 and the Insulin sensitivity. Insulin sensitivity will be estimated using the homeostasis model assessment (HOMA-IR) based on fasting C-peptid and glucose concentrations.'}, {'measure': 'Assocation between the serum or plasma concentration of metabolic, hormonal and inflammatory markers in maternal blood Versus the serum or plasma concentrations of the same markers in umbilical cord blood', 'timeFrame': 'At labour', 'description': 'Association between the metabolic, hormonal and inflammatory markers listed as Outcome 2 in maternal and umbilical cord blood'}, {'measure': 'Changes from baseline in the level, content and bioactivity of exosomes in serum and plasma.', 'timeFrame': 'Gestational week 28-36, at labour and 6 months postpartum', 'description': 'Exosomes will be isolated and profiling of the content will be performed using SWATH mass spectrometry and miRNA sequencing.'}, {'measure': 'Association between the level, content and bioactivity of exosomes in serum and plasma Versus Insulin sensitivity', 'timeFrame': 'Gestational week 28-36, at labour and 6 months postpartum', 'description': 'Exosomes will be isolated and profiling of the content will be performed using SWATH mass spectrometry and miRNA sequencing. Insulin sensitivity will be estimated using the homeostasis model assessment (HOMA-IR) based on fasting C-peptid and glucose concentrations.'}, {'measure': 'Association between the level, content and bioactivity of exosomes in serum and plasma in maternal blood Versus the level, content and bioactivity of exosomes in serum and plasma in umbilical cord blood', 'timeFrame': 'At labour', 'description': 'Exosomes will be isolated and profiling of the content will be performed using SWATH mass spectrometry and miRNA sequencing.'}, {'measure': 'Association between genetic variants related to overweight and diabetes Versus Insulin sensitivity', 'timeFrame': 'Gestational week 28-36', 'description': 'Genetic variants will be examined using whole genome analysis (Illumina Novaseq System). Insulin sensitivity will be estimated using the homeostasis model assessment (HOMA-IR) based on fasting C-peptid and glucose concentrations.'}, {'measure': 'Changes from baseline in body weight and body composition.', 'timeFrame': 'Gestational week 28-36 and 6 months postpartum', 'description': 'Body weight measured in kilograms. Body composition: Body fat percentage and muscle mass'}, {'measure': 'Changes from baseline in 24-hour ambulatory blood pressure (systolic and diastolic)', 'timeFrame': 'Gestational week 28-36 and 6 months postpartum', 'description': 'Blood pressure includes the measurement of both systolic and diastolic blood pressure (mmHg).'}, {'measure': 'Changes from baseline in cardiac function', 'timeFrame': 'Gestational week 28-36 and 6 months postpartum', 'description': 'Cardiac function will be evaluated through an echocardiography and a MRI scan of the heart'}, {'measure': 'Changes from baseline in the central aortic pressure waveform', 'timeFrame': 'Gestational week 28-36 and 6 months postpartum', 'description': 'Central aortic pressure waveform will be evaluated through a noninvasive measurement with SphygmoCor technology'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Diabetes Mellitus, Type 2', 'Gestational Diabetes', 'Overweight and Obesity', 'Pregnancy in Diabetic', 'Insulin Resistance', 'Insulin Sensitivity', 'Pregnancy, High Risk']}, 'descriptionModule': {'briefSummary': 'The aim of this study is to describe the metabolic changes during pregnancy in women with type 2 diabetes or gestational diabetes in order to detect the pathophysiological mechanisms behind severe insulin resistance during pregnancy as well as the short- and long term consequences for mother and child.\n\nIncluded pathophysiological mechanisms potentially associated with severe insulin resistance are: Maternal hormonal, inflammatory and metabolic markers in the blood, as well as the level, content and bioactivity of exosomes and genetic variants associated with overweight and diabetes.\n\nIn addition to the analysis on maternal blood, the same analysis will be performed on umbilical cord blood in order to determine the correlation between markers associated with insulin sensitivity in maternal and umbilical blood. Furthermore, fetal metabolic changes influence on fetal growth and development will be evaluated. Postpartum, the breast milk will also be examined for metabolic active substances that could influence the newborns growth and metabolism.\n\nInvestigating one potential short-term consequence of diabetes during pregnancy, the association between insulin resistance and structural and functional changes in the placenta will be examined as well as the consequences of such changes on fetal growth and development.\n\nInvestigating one potential long-term consequence of diabetes during pregnancy, the association between treatment with high doses of insulin during pregnancy and the future risk of developing cardiovascular diseases and heart failure will be examined.', 'detailedDescription': "This is a prospective observational study including app. 24 pregnant women from the outpatient clinics at Department of Obstetrics and Gynecology at Aalborg and Aarhus University Hospital.\n\nThe study includes 8 healthy women without pregestational or gestational diabetes, 8 women with gestational diabetes or type 2 diabetes with a total daily insulin dose \\<= 75 units/day and 8 women with gestational diabetes or type 2 diabetes with a total daily insulin dose \\>= 100 units/day.\n\nThere are three study days: One in gestational week 28-36 (day 1), one during labour (day 2) and one 6 months postpartum (day 3).\n\nHormonal profiles and inflammatory markers will be measured at all three study days. During labour both maternal and umbilical blood will be collected. The blood sample analysis will include HbA1c, glukose, insulin, C-peptid, human anti-insulin antibody, lipid profile, liver enzymes, creatinine, FGF-21, TSH, Cortisol, human chorionic gonadotropin, estradiol, progesterone, SHBG, prolactin, human placental lactogen, placental growth hormone, PAPP-A, sFlt-1, PP13, IGF-1, IGF-BP's, Leptin, Adiponectin, hs-CRP, IL-6, IL-10, IL-1α, IFN-ɣ, TNF-α, ICAM1, VCAM and CD163. In addition to this, exosomes will be isolated precisely and profiling of the content of exosomes will be performed using in vitro assays. Proteomics and miRNAs sequencing will be employed. Furthermore, whole genome analysis will be applied to find genetic variants associated with overweight and diabetes (genetic analysis will not be performed on umbilical cord blood). Insulin sensitivity will be estimated using the homeostasis model assessment, IS-HOMA, based on fasting C-peptid and glucose concentrations.\n\nIn addition to the blood samples, the following examinations will be performed at day 1:\n\n* Height, weight and bioelectrical impedance analysis\n* Urine sample (Albumin-to-creatinine ratio)\n* Blood pressure and 24-hour ambulatory blood pressure monitoring\n* Central arterial pressure waveform analysis (SphygmoCor)\n* Echocardiography\n* Fetal ultrasound\n* MRI scan of the placenta and heart\n\nIn addition to the blood samples, the following examinations will be performed at day 2:\n\n* Placenta will be collected for a postpartum histopathological examination\n* Breast milk (analyzed for lipid profile, leptin, adiponectin, prolactin, prolactin-binding protein, oxytocin, ghrelin, insulin, hs-CRP, IL-6, IL-10, IL-1α, IFN-ɣ, TNF-α, ICAM1, VCAM, CD163 and untargeted metabolomics)\n* Skinfold measurement of the newborn with a caliper\n\nIn addition to the blood samples, the following examinations will be performed at day 3:\n\n* Height, weight and bioelectrical impedance analysis\n* Urine sample (Albumin-to-creatinine ratio)\n* Blood pressure and 24-hour ambulatory blood pressure monitoring\n* Central arterial pressure waveform analysis (SphygmoCor)\n* Echocardiography\n* Breast milk (analyzed for lipid profile, leptin, adiponectin, prolactin, prolactin-binding protein, oxytocin, ghrelin, insulin, hs-CRP, IL-6, IL-10, IL-1α, IFN-ɣ, TNF-α, ICAM1, VCAM, CD163 and untargeted metabolomics)"}, 'eligibilityModule': {'sex': 'FEMALE', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'genderBased': True, 'samplingMethod': 'PROBABILITY_SAMPLE', 'studyPopulation': 'The study population consist of pregnant women followed at The Department of Gynaecology and Obstetrics at Aarhus University Hospital or Aalborg University Hospital. Cases are diagnosed with gestational diabetes or pregestational type 2 diabetes and are treated with a total daily insulin dose \\>= 100 units/day. Controls are either healthy without pregestational or gestational diabetes or diagnosed with gestational diabetes or pregestational type 2 diabetes and are treated with a total daily insulin dose \\<= 75 units/day', 'genderDescription': 'Only pregnant women are eligible for participation.', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Pregnant women at The Department of Gynaecology and Obstetrics at Aarhus University Hospital or Aalborg University Hospital.\n* Women have to be in 1 of 3 categories: Healthy without pregestational or gestational diabetes, type 2 diabetes treated with insulin or gestational diabetes treated with insulin.\n\nExclusion Criteria:\n\n* Age \\< 18 years\n* Not able to read and understand danish\n* Previous bariatric surgery\n* Treatment with systemic corticosteroids\n* Other severe chronic diseases such as inflammatory bowel disease, cystic fibrosis and type 1 diabetes'}, 'identificationModule': {'nctId': 'NCT04924504', 'briefTitle': 'Mechanisms Behind Severe Insulin Resistance During Pregnancy in Women With Glucose Metabolic Disorders (SIR-MET)', 'organization': {'class': 'OTHER', 'fullName': 'University of Aarhus'}, 'officialTitle': 'Mechanisms Behind Severe Insulin Resistance During Pregnancy in Women With Glucose Metabolic Disorders (SIR-MET)', 'orgStudyIdInfo': {'id': 'PADME'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'Type A', 'description': 'Healthy pregnant women without pregestational or gestational diabetes', 'interventionNames': ['Other: No interventions']}, {'label': 'Type B', 'description': 'Pregnant women with type 2 diabetes or gestational diabetes with a total daily insulin dose \\<= 75 units/day', 'interventionNames': ['Other: No interventions']}, {'label': 'Type C', 'description': 'Pregnant women with type 2 diabetes or gestational diabetes with a total daily insulin dose \\>= 100 units/day', 'interventionNames': ['Other: No interventions']}], 'interventions': [{'name': 'No interventions', 'type': 'OTHER', 'description': 'No interventions', 'armGroupLabels': ['Type A', 'Type B', 'Type C']}]}, 'contactsLocationsModule': {'locations': [{'zip': '8200', 'city': 'Aarhus', 'state': 'Aarhus N', 'status': 'RECRUITING', 'country': 'Denmark', 'contacts': [{'name': 'Anna S Koefoed, M.D.', 'role': 'CONTACT', 'email': 'annask@clin.au.dk', 'phone': '+45 25 32 35 38'}, {'name': 'Per G Ovesen, Prof., M.D.', 'role': 'CONTACT', 'email': 'perovese@rm.dk'}], 'facility': 'Aarhus University Hospital', 'geoPoint': {'lat': 56.15674, 'lon': 10.21076}}, {'zip': '9100', 'city': 'Aalborg', 'status': 'RECRUITING', 'country': 'Denmark', 'contacts': [{'name': 'Anne W Sørensen, M.D.', 'role': 'CONTACT', 'email': 'anns@rn.dk', 'phone': '+45 93 50 80 69'}], 'facility': 'Aalborg University Hospital', 'geoPoint': {'lat': 57.048, 'lon': 9.9187}}], 'centralContacts': [{'name': 'Anna S Koefoed, MD', 'role': 'CONTACT', 'email': 'annask@clin.au.dk', 'phone': '+45 93 50 80 69'}, {'name': 'Per G Ovesen, Prof., MD', 'role': 'CONTACT', 'email': 'perovese@rm.dk'}], 'overallOfficials': [{'name': 'Anna S Koefoed, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Aarhus University, Aarhus University Hospital'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Aarhus', 'class': 'OTHER'}, 'collaborators': [{'name': 'Aarhus University Hospital', 'class': 'OTHER'}, {'name': 'Aalborg University Hospital', 'class': 'OTHER'}, {'name': 'The University of Queensland', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR'}}}}