Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04924504
Other study ID # PADME
Secondary ID
Status Recruiting
Phase
First received
Last updated
Start date May 1, 2021
Est. completion date December 2023

Study information

Verified date November 2022
Source University of Aarhus
Contact Anna S Koefoed, MD
Phone +45 93 50 80 69
Email annask@clin.au.dk
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

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. Included 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. In 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. Investigating 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. Investigating 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.


Description:

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. The 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. There are three study days: One in gestational week 28-36 (day 1), one during labour (day 2) and one 6 months postpartum (day 3). Hormonal 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. In addition to the blood samples, the following examinations will be performed at day 1: - Height, weight and bioelectrical impedance analysis - Urine sample (Albumin-to-creatinine ratio) - Blood pressure and 24-hour ambulatory blood pressure monitoring - Central arterial pressure waveform analysis (SphygmoCor) - Echocardiography - Fetal ultrasound - MRI scan of the placenta and heart In addition to the blood samples, the following examinations will be performed at day 2: - Placenta will be collected for a postpartum histopathological examination - 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) - Skinfold measurement of the newborn with a caliper In addition to the blood samples, the following examinations will be performed at day 3: - Height, weight and bioelectrical impedance analysis - Urine sample (Albumin-to-creatinine ratio) - Blood pressure and 24-hour ambulatory blood pressure monitoring - Central arterial pressure waveform analysis (SphygmoCor) - Echocardiography - 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)


Recruitment information / eligibility

Status Recruiting
Enrollment 24
Est. completion date December 2023
Est. primary completion date December 2023
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Female
Age group 18 Years and older
Eligibility Inclusion Criteria: - Pregnant women at The Department of Gynaecology and Obstetrics at Aarhus University Hospital or Aalborg University Hospital. - 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. Exclusion Criteria: - Age < 18 years - Not able to read and understand danish - Previous bariatric surgery - Treatment with systemic corticosteroids - Other severe chronic diseases such as inflammatory bowel disease, cystic fibrosis and type 1 diabetes

Study Design


Intervention

Other:
No interventions
No interventions

Locations

Country Name City State
Denmark Aalborg University Hospital Aalborg
Denmark Aarhus University Hospital Aarhus Aarhus N

Sponsors (4)

Lead Sponsor Collaborator
University of Aarhus Aalborg University Hospital, Aarhus University Hospital, The University of Queensland

Country where clinical trial is conducted

Denmark, 

Outcome

Type Measure Description Time frame Safety issue
Primary Association between insulin sensitivity Versus structural and functional changes in the placenta 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. Gestational week 28-36
Secondary Association between structural and functional changes in the placenta Versus fetal growth and development 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. Gestational week 28-36
Secondary Changes from baseline in serum or plasma concentration of metabolic, hormonal and inflammatory markers 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.
Plasma concentrations of IL-6, IL-10, IL-1alpha, IFN-gamma, TNF-alpha, ICAM1, VCAM, LDL, HDL, Triglyceride, Gamma-Glutamyl Transferase, Thyrotropin, glucose and HbA1c.
Gestational week 28-36, at labour and 6 months postpartum
Secondary Assocation between the serum or plasma concentration of metabolic, hormonal and inflammatory markers Versus Insulin sensitivity 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. Gestational week 28-36, at labour and 6 months postpartum
Secondary 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 Association between the metabolic, hormonal and inflammatory markers listed as Outcome 2 in maternal and umbilical cord blood At labour
Secondary Changes from baseline in the level, content and bioactivity of exosomes in serum and plasma. Exosomes will be isolated and profiling of the content will be performed using SWATH mass spectrometry and miRNA sequencing. Gestational week 28-36, at labour and 6 months postpartum
Secondary Association between the level, content and bioactivity of exosomes in serum and plasma Versus Insulin sensitivity 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. Gestational week 28-36, at labour and 6 months postpartum
Secondary 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 Exosomes will be isolated and profiling of the content will be performed using SWATH mass spectrometry and miRNA sequencing. At labour
Secondary Association between genetic variants related to overweight and diabetes Versus Insulin sensitivity 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. Gestational week 28-36
Secondary Changes from baseline in body weight and body composition. Body weight measured in kilograms. Body composition: Body fat percentage and muscle mass Gestational week 28-36 and 6 months postpartum
Secondary Changes from baseline in 24-hour ambulatory blood pressure (systolic and diastolic) Blood pressure includes the measurement of both systolic and diastolic blood pressure (mmHg). Gestational week 28-36 and 6 months postpartum
Secondary Changes from baseline in cardiac function Cardiac function will be evaluated through an echocardiography and a MRI scan of the heart Gestational week 28-36 and 6 months postpartum
Secondary Changes from baseline in the central aortic pressure waveform Central aortic pressure waveform will be evaluated through a noninvasive measurement with SphygmoCor technology Gestational week 28-36 and 6 months postpartum
See also
  Status Clinical Trial Phase
Active, not recruiting NCT05666479 - CGM Monitoring in T2DM Patients Undergoing Orthopaedic Replacement Surgery
Completed NCT05647083 - The Effect of Massage on Diabetic Parameters N/A
Active, not recruiting NCT05661799 - Persistence of Physical Activity in People With Type 2 Diabetes Over Time. N/A
Completed NCT03686722 - Effect of Co-administration of Metformin and Daclatasvir on the Pharmacokinetis and Pharmacodynamics of Metformin Phase 1
Completed NCT02836704 - Comparison of Standard vs Higher Starting Dose of Insulin Glargine in Chinese Patients With Type 2 Diabetes (Glargine Starting Dose) Phase 4
Completed NCT01819129 - Efficacy and Safety of FIAsp Compared to Insulin Aspart in Combination With Insulin Glargine and Metformin in Adults With Type 2 Diabetes Phase 3
Completed NCT04562714 - Impact of Flash Glucose Monitoring in People With Type 2 Diabetes Using Non-Insulin Antihyperglycemic Therapy N/A
Completed NCT02009488 - Treatment Differences Between Canagliflozin and Placebo in Insulin Secretion in Subjects With Type 2 Diabetes Mellitus (T2DM) Phase 1
Completed NCT05896319 - Hyaluronic Acid Treatment of the Post-extraction Tooth Socket Healing in Subjects With Diabetes Mellitus Type 2 N/A
Recruiting NCT05598203 - Effect of Nutrition Education Groups in the Treatment of Patients With Type 2 Diabetes N/A
Completed NCT05046873 - A Research Study Looking Into Blood Levels of Semaglutide and NNC0480-0389 When Given in the Same Injection or in Two Separate Injections in Healthy People Phase 1
Terminated NCT04090242 - Impact of App Based Diabetes Training Program in Conjunction With the BD Nano Pen Needle in People With T2 Diabetes N/A
Completed NCT04030091 - Pulsatile Insulin Infusion Therapy in Patients With Type 1 and Type 2 Diabetes Mellitus Phase 4
Completed NCT03620357 - Continuous Glucose Monitoring & Management In Type 2 Diabetes (T2D) N/A
Completed NCT03604224 - A Study to Observe Clinical Effectiveness of Canagliflozin 300 mg Containing Treatment Regimens in Indian Type 2 Diabetes Participants With BMI>25 kg/m^2, in Real World Clinical Setting
Completed NCT01696266 - An International Survey on Hypoglycaemia Among Insulin-treated Patients With Diabetes
Completed NCT03620890 - Detemir Versus NPH for Type 2 Diabetes Mellitus in Pregnancy Phase 4
Withdrawn NCT05473286 - A Research Study Looking at How Oral Semaglutide Works in People With Type 2 Diabetes in Germany, as Part of Local Clinical Practice
Not yet recruiting NCT05029804 - Effect of Walking Exercise Training on Adherence to Disease Management and Metabolic Control in Diabetes N/A
Completed NCT04531631 - Effects of Dorzagliatin on 1st Phase Insulin and Beta-cell Glucose Sensitivity in T2D and Monogenic Diabetes Phase 2