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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 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: October 24, 2014
Last verified: October 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. Microalbuminuria predicts the development of pre-eclampsia in pregnant patients with pregestational diabetes type 1. The investigators hypothesize that urine-plasmin excreted in the kidneys, when proteinuria occurs, could be the cause. The investigators want to test the correlation between measurable plasmin/plasminogen in the urine early in pregnancy and the development of preeclampsia in pregnant 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 whether there is a measurable correlation between plasmin/plasminogen, abnormally excreted in the kidneys, and the development of pre-eclampsia in pregnant women with Type 1 diabetes.

Hypothesis:

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

If a correlation between excreted plasmin/plasminogen, in urine, in patients with type 1 diabetes and development of preeclampsia, are seen, proteases might be used as a marker for pre-eclampsia in this group of patients. Prospectively perhaps also as a marker for disease severity.

In these high risk groups it is possible that outpatient visits could be optimized and thus 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 pregnancy week 9.

Selection of patients:

Patients are selected from Gynecological- obstetric department, Aarhus University hospital - Skejby, and Gynecological- Obstetric department, Odense University Hospital. To be included they must be singleton-pregnant, have turned 18 years and have Type 1 diabetes.

Background information:

Date of birth, sex, weight, height, BMI, smoking status, current medical treatment, duration of diabetes and parity are registered.

Length of gestation, placental weight, way of delivery (natural birth or cesarean section), umbilical cord pH, apgar score and infant weight are registered post-partum.

Effect variables:

Clinical:

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

Blood test measurements:

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

Measurements in 50 ml "spot urine":

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

Study process:

Collection of blood- and spot-urine samples:

Urine-samples are collected in pregnancy week 9-14. Blood pressure is measured. Samples and blood-pressures are re-collected in pregnancy-week 20, 28,32, 36 and perhaps 38.

Following outcomes are observed: 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 estimation:

Similar (Danish) observational prospective studies on urine- biomarkers (including albumin) ability to predict preeclampsia/preterm delivery, in patients with pre-gestational type 1 diabetes, have been made. They achieved high significance data with spot-samples of 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 University Hospitals (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,
  • Pregestational type 1 diabetes. Gestation week 8-14.

Exclusion Criteria:

  1. Possible comorbidity like systemic lupus erythematosus (SLE), hypertension and rheumatoid arthritis.
  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. It is therefore possible to include these patients.

Thyroid diseases are NOT a reason for exclusion.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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@clin.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: October 24, 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
Autoimmune Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Hypertension, Pregnancy-Induced
Immune System Diseases
Metabolic Diseases
Pregnancy Complications
Plasminogen
Cardiovascular Agents
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014