Clinical trial NCT01821053: Urine-plasminogen as a Predictor for Development Of Preeclampsia in Pregnant Women With Type 1 Diabetes Mellitus
Official title: Urine-plasminogen as a Predictor for Development Of Preeclampsia in Pregnant Women With Type 1 Diabetes Mellitus
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Preeclampsia
Type 1 Diabetes
Keywords: Preeclampsia
Pregestational Type 1 diabetes
diabetes mellitus
proteinuria
plasminogen
plasmin
renin
aldosterone
angiotensin
epithelial sodium channel
ENaC
Lead sponsor: Odense University Hospital
Sponsor class: OTHER
Collaborators: name: Aarhus University Hospital
First posted: 2013-03-29
Enrollment: 85
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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 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.

Primary outcomes:
measure: preeclampsia
timeFrame: 3 years
Secondary outcomes:
measure: preterm delivery
timeFrame: 3 years
measure: light for gestational age
timeFrame: 3 years
Other outcomes:
Locations:
city: Skejby
country: Denmark
facility: Gynelogical Obstetrical Department
state: Aarhus N
Study officials:
affiliation: cardiovascular and renal research department, Odense University Hospital
name: Boye L. Jensen, Professor
role: STUDY_DIRECTOR
References:
citation: Nielsen LH, Jensen BL, Fuglsang J, Andersen LLT, Jensen DM, Jorgensen JS, Kitlen G, Ovesen P. Urine albumin is a superior predictor of preeclampsia compared to urine plasminogen in type I diabetes patients. J Am Soc Hypertens. 2018 Feb;12(2):97-107. doi: 10.1016/j.jash.2017.12.003. Epub 2017 Dec 13.