We hypothesize that formerly pre-eclamptic women have persistently increased angiotensin II sensitivity, sodium sensitivity, insulin resistance and sympathetic nerve activity together initially leading to susceptibility for early renal disease and…
ID
Source
Brief title
Condition
- Other condition
- Pregnancy, labour, delivery and postpartum conditions
Synonym
Health condition
Hart- en vaatziekten
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To compare mean 24-hour, day- and night time SBP and DBP in patients with a
history of PE after 8 weeks of treatment with placebo, losartan, moxonidine and
low sodium diet.
Secondary outcome
To compare changes in the following parameters in women with a history of PE
after 8 weeks of treatment with placebo, losartan, moxonidine and low sodium
diet: RAAS-activity, SNS-activity, endothelial function, arterial stiffness,
lipid metabolism, insulin sensitivity, oxidative stress and systemic
inflammation.
Background summary
There is considerable concern about the link between preeclampsia (PE) and the
subsequent risk for developing cardiovascular disease and renal disease later
in life. The risk for end stage renal disease after PE 8-15 fold increased. A
growing body of evidence suggest that shared metabolic, immunological and
vascular pathways are responsible for PE as well as future cardiovascular risk
of women. Possibly PE itself contributes to the risk as well. Mechanistic
studies have shown that marked changes in the renin-angiotensin aldosterone
system (RAAS), sympathetic nerve system (SNS) and sodium sensitivity of blood
pressure are present in women with a history of PE. All these pathways are
known to contribute to development of cardiovascular and renal disease.
Study objective
We hypothesize that formerly pre-eclamptic women have persistently increased
angiotensin II sensitivity, sodium sensitivity, insulin resistance and
sympathetic nerve activity together initially leading to susceptibility for
early renal disease and subsequently hypertension, chronic kidney disease and
cardiovascular disease. Possibly early intervention in these systems can lower
blood pressure effectively a give specific tools for primary prevention
strategies.
Study design
A randomized, placebo-controlled, double blind, 4-period, cross-over trial.
Intervention
Once daily doses of losartan (100 mg), moxonidine (0,4 mg), low sodium diet (50
mmol NaCl/24 hour) and placebo following standardised 8-week treatment
schedules. Participants receive all four interventions in a randomized and
blinded (except from low sodium diet).
Study burden and risks
All study medication is registered for the treatment of hypertension and
effects on blood pressure are minimal (5-10 mmHg lowering). Participants are
asked to come a total of 6 study visits to the UMC Utrecht. Prior to 4 of these
visits, patients need to have fasted for 13 hours. Most measurements are non
invasive, but also some venous blood samples (45 mL during each of the visits
3-6) will be drawn.
Participants do not directly benefit from study participation. The scientific
value, however, is considerable. After the study is ended (last participant,
last measurement), participants can choose to receive an overview of some of
their metabolic parameters, in order to optimize their future cardiovascular
disease risk management.
Lundlaan 6
Utrecht 3584 EA
NL
Lundlaan 6
Utrecht 3584 EA
NL
Listed location countries
Age
Inclusion criteria
1. Patient is a female between 18 and 45 years of age on the day of signing informed consent.
2. Have a recent history of preeclampsia that is defined as gestational hypertension and concomitant proteinuria in the second half of pregnancy. Gestational hypertension was defined according to the criteria of the International Society for the Study of Hypertension in Pregnancy (ISSHP) as diastolic blood pressure above 90 mmHg and/or systolic blood pressure above 140 mmHg, measured on two or more separate occasions at least 4 hours apart. Proteinuria was diagnosed with urinary protein was above 300 mg per 24 hour or above 2+ at dipstick urinalysis 17
3. All patients should fulfil the following diagnostic criterion:
- Off treatment SBP > 120 mmHg and/or DBP > 80 mmHg during both visits.
4. Blood pressure is assessed by office readings in accordance with current guidelines for hypertension diagnosis18. The patient needs to be seated some minutes before and during the measurement. The cuff size should be adjusted to the patients* arm circumference and needs to be on the same height level as the patients* sternum during the measurements. Blood pressure is determined to a 2-mmHg accuracy-level. Blood pressure is measured on both arms during the first visit. If both measurements differ more than 10 mmHg, the highest value is taken. After at least 15 seconds, the measurement is repeated during the same visit. The highest mean of the two measurements on the same arm is considered as the actual blood pressure value.
5. Patient understands the study procedures, alternative treatments available, and risks involved with the study and voluntarily agrees to participate by giving written informed consent.
Exclusion criteria
1. SBP >180 mmHg and/or DBP >110 mmHg during one or more screening measurements.
2. Current pregnancy
3. Use of *recreational* or illicit drugs
4. Recent history (within the last year) of alcohol abuse or dependence.
5. Several medical conditions as depicted in the protocol
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-002524-27-NL |
| CCMO | NL49102.041.14 |
| OMON | NL-OMON28431 |