Preeclampsia Postpartum
Conditions
Brief summary
Women who develop preeclampsia during pregnancy are more likely to develop and die of cardiovascular disease later in life, even if they are otherwise healthy. The reason why this occurs is unclear but may be related to blood vessel damage and increased inflammation that occurs during the preeclamptic pregnancy and persists postpartum. The purpose of this investigation is to determine the mechanisms contributing to this lasting blood vessel damage and to test whether taking a medication that blocks angiotensin II receptors (losartan) decrease these negative effects in women who have had preeclampsia. Identification of these mechanisms and treatment strategies may lead to better clinical management,of cardiovascular disease risk in these women. In this study we use the blood vessels in the skin as a representative vascular bed. Using a minimally invasive technique (intradermal microdialysis for the local delivery of pharmaceutical agents) we examine the blood vessels in a nickle-sized area of the skin in women who have had preeclampsia. We make these measurements after the subjects take a placebo and after they take losartan (an angiotensin II receptor blocker) to test whether this treatment improves vascular function in these women. As a compliment to these measurements, we also draw blood from the subjects and isolate the inflammatory cells to test how sensitive their inflammatory responses are following the placebo and the losartan treatment.
Interventions
DRUGLosartan Potassium
subjects ingest 50mg losartan potassium tablet daily for 6 weeks
DRUGPlacebo
subjects ingest placebo tablet daily for 6 weeks
Sponsors
Anna Stanhewicz, PhD
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
Post-partum women, * 18 years or older, * who have delivered within 24 months of the study visit * who have had a preeclamptic pregnancy diagnosed by their obstetrician and confirmed according to the American College of Obstetricians and Gynecologists criteria for preeclampsia. \[This information will be self-reported by the subjects.\] * Using an effective method of birth control and not planning to become pregnant in the next 6 months.
Exclusion criteria
* skin diseases, * current tobacco use, * diagnosed or suspected hepatic or metabolic disease including chronic kidney disease (CKD) defined as reduced eGFR \< 60 mL/min/1.73m2, * statin or other cholesterol-lowering medication, * current antihypertensive medication, * history of hypertension prior to pregnancy, * history of gestational diabetes, * current pregnancy or breastfeeding, * body mass index \<18.5 kg/m2, * allergy to materials used during the experiment.(e.g. latex), * known allergies to study drugs.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cutaneous Conductance (%Maximum) Response to Acetylcholine | immediately following 6 weeks of oral treatment (losartan or placebo) | Cutaneous vascular vasodilator response to exogenous acetylcholine perfusion; measured with laser-Doppler flowmetry during intradermal microdialysis delivery of acetylcholine alone or co-infused with L-NAME. Cutaneous conductance is calculated (laser-Doppler flux/mean arterial pressure) and normalized to site specific maximal dilation (%maximum). |
| Cutaneous Conductance (%Baseline) Response to Angiotensin II | immediately following 6 weeks of oral treatment (losartan or placebo) | Cutaneous vascular constrictor response to exogenous ang II perfusion; measured by laser-Doppler flowmetry during intradermal microdialysis delivery of angiotensin II. Cutaneous conductance is calculated (laser-Doppler flux/mean arterial pressure) and normalized to site-specific baseline conductance (%baseline) measured on the study day before the perfusion of angiotensin II. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants All participants were randomized to receive both interventions. | 11 |
| Total | 11 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 33 years STANDARD_DEVIATION 6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Region of Enrollment United States | 11 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 11 |
| other Total, other adverse events | 0 / 11 | 0 / 11 |
| serious Total, serious adverse events | 0 / 11 | 0 / 11 |
Outcome results
Primary
Cutaneous Conductance (%Baseline) Response to Angiotensin II
Cutaneous vascular constrictor response to exogenous ang II perfusion; measured by laser-Doppler flowmetry during intradermal microdialysis delivery of angiotensin II. Cutaneous conductance is calculated (laser-Doppler flux/mean arterial pressure) and normalized to site-specific baseline conductance (%baseline) measured on the study day before the perfusion of angiotensin II.
Time frame: immediately following 6 weeks of oral treatment (losartan or placebo)
Population: all participants completed both treatments in randomized, blinded, cross-over design
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan | Cutaneous Conductance (%Baseline) Response to Angiotensin II | 76.7 % of baseline cutaneous conductance | Standard Deviation 29.1 |
| Placebo | Cutaneous Conductance (%Baseline) Response to Angiotensin II | 53.8 % of baseline cutaneous conductance | Standard Deviation 27.3 |
Primary
Cutaneous Conductance (%Maximum) Response to Acetylcholine
Cutaneous vascular vasodilator response to exogenous acetylcholine perfusion; measured with laser-Doppler flowmetry during intradermal microdialysis delivery of acetylcholine alone or co-infused with L-NAME. Cutaneous conductance is calculated (laser-Doppler flux/mean arterial pressure) and normalized to site specific maximal dilation (%maximum).
Time frame: immediately following 6 weeks of oral treatment (losartan or placebo)
Population: All participants completed both treatments in randomized, blinded, cross-over design
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan | Cutaneous Conductance (%Maximum) Response to Acetylcholine | 89.4 % of maximal cutaneous conductance | Standard Deviation 22.6 |
| Placebo | Cutaneous Conductance (%Maximum) Response to Acetylcholine | 72.5 % of maximal cutaneous conductance | Standard Deviation 16.5 |