- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04907708
Comparative Effects of Metformin and Insulin on Stereological Studies and Immunohistochemistry of Placenta
Comparative Studies of Metformin and Insulin on Stereological Studies and Immunohistochemistry of Placenta
Study Overview
Status
Intervention / Treatment
Detailed Description
Diabetes mellitus is a group of metabolic disorder with relative or absolute deficiency of insulin. Pregnancy is a potentially glucose intolerant condition as insulin sensitivity decreases with the progress of pregnancy leading to the development of gestational diabetes mellitus (GDM). It is diagnosed in approximately 3-9% of pregnancies and is growing in prevalence. In Pakistan the recent prevalence of GDM is reported to be 3-3.45% but the complications are much higher due to poor glycemic control, lack of awareness and inadequate medical facilities. Placenta is an important feto-maternal organ which is responsible for nutrition of the fetus. It also provides the retrospective information regarding infant's prenatal development. Structurally, human placenta is a complex vascular organ that allows exchange of nutrients and chemicals between fetal and maternal blood. Proper development and maturity of placenta are strongly connected with fetal growth and survival.
GDM produces anatomical and physiological alterations in placenta. This can be related to altered levels of fetal insulin and multiple growth factors such as placental vascular endothelial growth factor (VEGF), Insulin like growth factors (IGF and IGF binding proteins) which regulate the fetal and placental development. Morphologically, diabetic placentae are larger in size and volume. Microscopically, diabetic placenta shows degenerative alternations such as villous fibrinoid necrosis, chorangiosis, villous immaturity, calcification and syncytial knots formation which show intense hypoxia of the placental tissues.
Nutritional therapy (diet control) is foremost important for achieving target glucose values during pregnancy but in uncontrolled cases pharmacological intervention is required. Parental Insulin is the traditional therapy in such circumstances, but is an expensive medication and is associated with high incidence of neonatal and maternal hypoglycemia, still births, neonatal morbidity and mortality. It is documented to produce many placental alterations such as immature villi, hemorrhages, edema, cystic changes and fibrinoid necrosis. It has been postulated that the reason behind all these hypoxic changes are the variation in the blood glucose level that occur in the maternal blood as sugar level suddenly dropped soon after Insulin injection and are at highest just before the next dose of Insulin.
The use of oral anti-diabetic medications such as Metformin in the management of gestational diabetes has increased over the past several years. Recent studies has established that Metformin can be a better option for GDM as it well controls glycemia (produces euglycemic) with good pregnancy outcomes. Metformin is an oral anti-diabetic drug from biguanide group; work by improving insulin sensitivity, reducing hepatic gluconeogenesis and also by increasing peripheral glucose uptake and utilization. It is now been upgraded to category B drug as is not associated with teratogenic effects. But what are the effects of Metformin on stereological morphometric study and immunochemistry of placental tissues were left to be evaluated. Stereology provides practical measurements and significant approach for obtaining quantitative estimates of small structures on histological slides. In placental tissue it is performed to obtain unbiased quantitative estimates of placental components that inform about development and also estimate of structural parameters that have direct influence on placental functional capacity. Immunohistochemistry or immunofluorescence of tissue sections also provide valuable insight to placental structure and protein expression with three-dimensional spatial information, including morphology that cannot be obtained on microscopy.
With this background knowledge, study was designed with the following objectives:
- To evaluate the placental gross and microscopic changes in normal, diet control, Metformin and Insulin treated in newly enrolled GDM females
- To evaluate stereological morphometric details of placenta in normal, diet control, Metformin and Insulin all enrolled females
- To evaluate immunohistochemistry of placental tissues in normal, diet control, Metformin and Insulin in all enrolled females
- To compare the placental morphology, stereology and immunohistochemistry with in the groups.
- To evaluate the fetal and maternal outcome in normal, diet control, Metformin and Insulin treated gestational diabetics.
- To correlate the placental morphology with the fetal and maternal outcome in Metformin and Insulin treated gestational diabetics
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Sindh
-
Karachi, Sindh, Pakistan, 75510
- Jinnah Post Graduate Medical Centre
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
For this study placentae were collected from:
- Patients who were diagnosed as GDM during second trimester screening for FBS and RBS, confirmed further by OGCT and OGTT.
- GDM patients who signed the written informed consent.
- GDM patients who were in ages between 18 years and 40 years and had no other comorbid such hypertension, CVD etc
- Full term GDM patients with singleton pregnancy (37 weeks and above)
- GDM patients whose placenta were preserved within 30-40 minutes of delivery.
Exclusion Criteria:
Placentae were not collected from:
- GDM Patients with ages less than 18 or more than 40 years
- GDM females with some co-morbid and complications (e.g. hypertension, CVD, diabetes type 1 or diabetes type 2 before gestation, abnormal Urea Creatinine Electrolyte (UCE) and Liver function test (LFTs).
- GDM Patients who delivered pre-termed (< 37 weeks of gestation) or post termed (>42 weeks of gestation)
- GDM patients with twin pregnancy.
- GDM Patients if not preserved in the formalin properly within 30-40 minutes of delivery.
- GDM females who were given combined (Metformin and insulin) therapy.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
No Intervention: Normal healthy controls
females in second trimester with normal glucose levels
|
|
No Intervention: Diet controlled
females in second trimester with blood sugar levels below 129mg/dl
|
|
Experimental: Metformin
females in second trimester with blood sugar levels above 130mg/dl treated with Metformin
|
Euglycemic agent
|
Experimental: Insulin
females in second trimester with blood sugar levels above 130mg/dl being treated with Insulin
|
Hypoglycemic agent
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Mean morphometric diffusion capacity for oxygen (MMDC) in placental tissues
Time Frame: 15 months
|
With detailed stereological assessment MMDC can be calculated for the placenta to visualize which group placenta allows better diffusion of oxygen
|
15 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of immuno-antigens present in placental tissue
Time Frame: 15 months
|
The percentage of immuno-antigens on the placental tissue is related to the hypoxic and vascular changes in the placenta.
|
15 months
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: KAUSER AAMIR, Ph.D, BMSI, JPMC,KARACHI
Publications and helpful links
Helpful Links
- Belkacemi, L., Kjos, S., Nelson, D. M., & Desai, M. (2013). Reduced apoptosis in term placentas from gestational diabetic pregnancies. Journal of Developmental Origins of Health and Disease, 4 (3), 256-265.
- Casson, I. F., Clarke, C, A., Howard, C.V., McKendrick, O., Pennycook, S., Pharoah, P.O.D. (1997). Outcomes of pregnancy in insulin dependent diabetic women: results of a five-year population cohort study, British Medical Journal, 315, 275.
- The Incidence of Placental Abnormalities, Maternal and Cord Plasma Malondialdehyde and Vascular Endothelial Growth Factor Levels in Women with Gestational Diabetes Mellitus and No
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- UKarachi
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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