Urine-plasminogen as a Predictor for Development Of Preeclampsia in Pregnant Women With Type 1 Diabetes Mellitus

This study is currently recruiting participants.
Verified March 2014 by Odense University Hospital
Sponsor:
Collaborator:
Aarhus University Hospital
Information provided by (Responsible Party):
Lise Hald Nielsen, Odense University Hospital
ClinicalTrials.gov Identifier:
NCT01821053
First received: March 26, 2013
Last updated: March 17, 2014
Last verified: March 2014
  Purpose

A tonic active epithelial Na+ channel (ENaC) in pre-eclampsia (PE) escaped normal hormonal control may offer an attractive explanatory model for the pathophysiology of established PE. The channel is activated by plasmin. Because microalbuminuria in pregnant pregestational diabetes patients predicts the development of preeclampsia, we believe that it is caused by plasmin(plasminogen) lose from plasma to the urine. The investigators want to test the correlation between measurable plasmin/plasminogen in the urine early in pregnancy and the development of preeclampsia in patients with type 1 diabetes.


Condition
Preeclampsia
Type 1 Diabetes

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Urine-plasminogen as a Predictor for Development Of Preeclampsia in Pregnant Women With Type 1 Diabetes Mellitus

Resource links provided by NLM:


Further study details as provided by Odense University Hospital:

Primary Outcome Measures:
  • preeclampsia [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    The development of preeclampsia, defined by hypertension ( > 140/90 mmHg) and proteinuria ( >0,3 g/24 hour).


Secondary Outcome Measures:
  • preterm delivery [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    post-partum registration of preterm delivery

  • light for gestational age [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    post-partum registration of "light for gestational age"


Biospecimen Retention:   Samples With DNA

whole blood serum plasma urine


Estimated Enrollment: 130
Study Start Date: June 2013
Estimated Study Completion Date: February 2016
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
pregestational type 1 diabetes
It is an observational study. No intervention is made.

  Hide Detailed Description

Detailed Description:

Study aim and hypothesis:

Aim:

To test if there is a measurable correlation between plasmin/plasminogen abnormally excreted by the kidneys to the urine and the development of preeclampsia at pregnant women with Type 1 diabetes.

Hypothesis:

1. The amount of proteases ( plasmin/plasminogen ) excreted in urine predicts the development of preeclampsia at pregnant patients with type 1 diabetes.

If we see a correlation between the excretion of plasmin/plasminogen in urine in patients with type 1 diabetes and the development of preeclampsia, the proteases might be used as a marker for these patients in the diabetes group that develop the disease and eventually also as a marker for the severity.

In these high risk groups it is possible that we would be able to optimize their outpatient visits even more in trying to lower the amount of preterm births.

Study design:

The study is an observational, longitudinal - prospective study. Women with pregestational type 1 diabetes are included when they show up for their first outpatient pregnancy visit around the 9th weeks gestation.

Selection of patients:

The selection of patients is based on pregnant outpatients with Type 1 diabetes, over 18 years, from Gynecological- obstetric department, Aarhus University hospital - Skejby, and Gynecological- Obstetric department, Odense University Hospital.

Background information:

Registration of date of birth, sex, weight, height, hip-waist ratio, and smoking status will be noted.

Furthermore, we will register current medical treatment, duration of diabetes, pregestational bloodpressure, parity and HbA1c.

Also post-partum registration of length of gestation, weight of placenta, way of delivery (natural birth or cesarean section), umbilical cord pH, apgar score and the infant weight will be noted.

Effect variable:

Clinical:

Weight, height, BMI, smoking status, microalbuminuria/proteinuria . Blood pressure (systolic, diastolic, mean arterial pressure). Weight of placenta

Measurements in blood tests:

Se-creatinine, p-Na+, p-K+. P-plasminogen, P-albumin, Aldosterone.

Measurements in 50 ml newly "spot urine":

Plasmin, plasminogen, ENaC peptide fragment (analyses in location of development,) Proteolytic activity, Prostatin, Creatinine, Na+, K+, Aldosterone, Albumin

Study process:

Visits, including bloodsampels and spoturine collection:

Women with pregestational type 1 diabetes are included. In first trimester, around pregnancy week 9-14 an urinesampel is collected. Blood pressure is measured and urine plasmin/plasminogen, albumin and aldosterone are analyzed. After that urine- and blood samples are collected in pregnancyweek 20, 28,32, 36 and perhaps 38. Plasmin/plasminogen analyses, regarding to detect the excretion compared to the development in PE, are made. Around pregnancy week 28 a single 24 hour blood pressure measurement are done according to observe the daily variation.

Following outcomes are observed: The development of preeclampsia, defined by hypertension ( > 140/90 mmHg), and proteinuria ( >0,3 g/24 hour). Preterm delivery and light for gestational age.

Data- analysis methods:

This is an observational longitudinal-prospective study which includes approximately 130 pregnant patients with Type 1 diabetes. Patients are included from Skejby and Odense University Hospitals in cooperation.

Results are evaluated statistically by uni - and multivariate logistic regression analysis.

Population size evaluation:

Similar (Danish) observational prospective studies of urine- biomarkers (including albumin) ability to predict preeclampsia/preterm delivery in patients with pregestational type 1 diabetes have achieved high significance data with spotsamples at 130 -170 patients. With the participation of two centers it seems realistic and adequately to include 130 patients within the settings of a Ph. D. study. Every year an amount of 50-60 patients are seen in the outpatient ward at Skejby- and Odense Universityhospitals (in all approximately 100-120 patients).

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

pregnant women with pregestational type 1 diabtes are included when they show up for their first outpatient pregnancy visit around the 9th weeks gestation.

Criteria

Inclusion Criteria:

  • singleton gravida,
  • over 18 years,
  • with pregestational type 1 diabetes. Gestation week 8-14.

Exclusion Criteria:

  1. Possible comorbidity like systemic lupus erythematosus (SLE), hypertension and rheumatoid arthritis are reasons for exclusion regarding investigation of the hypothesis.
  2. Organic or systematic diseases with clinical relevance ( ex. Malignity)

However it has to be mentioned that quite some patients have thyroid diseases with no impact on the kidneys nor hypertension and therefore it is possible to include these patients.

Thyroid diseases are NOT a reason for exclusion.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01821053

Locations
Denmark
Gynelogical Obstetrical Department Recruiting
Skejby, Aarhus N, Denmark, 8200
Contact: Lise H. Nielsen, doctor    +4553347735    lihn@ki.au.dk   
Contact: Per Ovesen, doctor    +4561669728    Per.Ovesen@dadlnet.dk   
Principal Investigator: Lise H. Nielsen, Doctor         
Sponsors and Collaborators
Odense University Hospital
Aarhus University Hospital
Investigators
Study Director: Boye L. Jensen, Professor cardiovascular and renal research department, Odense University Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Lise Hald Nielsen, doctor, Ph.D student, Odense University Hospital
ClinicalTrials.gov Identifier: NCT01821053     History of Changes
Other Study ID Numbers: 1-10-72-1-13
Study First Received: March 26, 2013
Last Updated: March 17, 2014
Health Authority: Denmark: Danish Dataprotection Agency

Keywords provided by Odense University Hospital:
Preeclampsia
Pregestational Type 1 diabetes
diabetes mellitus
proteinuria
plasminogen
plasmin
renin
aldosterone
angiotensin
epithelial sodium channel
ENaC

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Pre-Eclampsia
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Hypertension, Pregnancy-Induced
Pregnancy Complications
Plasminogen
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Hematologic Agents

ClinicalTrials.gov processed this record on April 17, 2014