Measurement of B Lymphocyte Stimulator (BLyS) in Peripheral Blood From Pregnant and Nonpregnant Women

Maternal Serum BLyS Levels Throughout Pregnancy



Sponsors


Source

University of Southern California

Oversight Info

Has Dmc

No

Is Fda Regulated Drug

No

Is Fda Regulated Device

No


Brief Summary

Background and rationale: B lymphocyte stimulator (BLyS) is a potent B cell survival factor
that has been found to be elevated in patients with inflammatory conditions, such as systemic
lupus and rheumatoid arthritis. Because of the immunologic changes associated with pregnancy,
including changes in levels of T and B lymphocytes, it is postulated that BLyS levels would
be altered in pregnancy compared to the non-pregnant state.

Objectives: The primary objective of this study is to assess the levels of BLyS in each
trimester of pregnancy. Secondary objectives include evaluation of an association between
BLyS levels and adverse pregnancy events; comparison of BLyS levels between healthy pregnant
women and pregnant women with a medical or obstetric conditions; and, assessment of APRIL
levels and comparison between APRIL levels and BLyS levels in study subjects.

Study population: Pregnant and non-pregnant women receiving care in the outpatient Obstetrics
and Gynecology clinics at LAC+USC Medical Center.

Study methodology: Peripheral blood samples will be drawn from pregnant women and
non-pregnant controls. Pregnant women will have blood drawn each trimester, at delivery, and
postpartum, and control subjects will have blood drawn once, upon enrollment in the study.

Study outcomes: BLyS and APRIL levels during each trimester, postpartum and in cord blood
will be compared between healthy pregnant women, pregnant women with a medical condition, and
healthy non-pregnant controls. Additionally, pregnancy outcomes will be recorded to determine
whether BLyS or APRIL levels correlate with adverse events.

Statistics: Continuous data will be analyzed by Student t-test or logistic regression, where
appropriate. Categorical data will be analyzed using Chi square.

Detailed Description

The investigators performed a prospective observational study of pregnant women presenting
for prenatal care at Los Angeles County+University of Southern California Obstetrics clinics.
Subjects were recruited from October 2011 through June 2013. Pregnant women were recruited at
the time of their first prenatal visit. Women under the age of 18 and women carrying a fetus
with a known major congenital anomaly were excluded. A control group of premenopausal
nonpregnant (NP) women without known medical or rheumatic illnesses was recruited from the
Los Angeles County+University of Southern California Gynecology outpatient clinics. Informed
consent was obtained from each study participant before enrollment. Approval for this study
was obtained from the Los Angeles County+University of Southern California Institutional
Review Board.

A participant was classified as having gestational hypertension if the participant had ≥2
episodes of new-onset HTN (systolic blood pressure >140 mm Hg or diastolic blood pressure >90
mm Hg) after 20 weeks of pregnancy. PE was defined as gestational hypertension that was
accompanied by proteinuria of at least 300 mg in a 24-hour urine collection or a
protein/creatinine ratio ≥0.3. HELLP syndrome was diagnosed when a woman had laboratory
evidence of hemolysis, a platelet count <100,000/μL, and serum levels of aspartate
aminotransferase and alanine aminotransferase that were greater than or equal to twice normal
values. Superimposed preeclampsia was diagnosed in a participant with CHTN when the
participant experienced an acute exacerbation of hypertension after 20 weeks of gestation. In
a participant without preexisting proteinuria, new-onset proteinuria was also required for
the diagnosis.

Patient characteristics were obtained through patient interviews and medical chart review.
Maternal venous blood was collected by venipuncture at least once per trimester, on admission
for delivery, and postpartum. The first trimester was defined as <14 gestational weeks, the
second trimester as 14 0/7 to 27 6/7 gestational weeks, and the third trimester as 28 0/7
gestational weeks to delivery. Postpartum samples were collected before hospital discharge
after delivery.

Blood samples were collected in sterile tubes without additives and refrigerated until
processing. Sera were routinely isolated from the clotted blood samples within 12 to 24 hours
and were aliquotted and stored at −80°C. Serum BAFF levels were measured in a blinded fashion
using a sandwich ELISA.

Chi-squared or Fisher exact testing was used for categorical variables, and Kruskal-Wallis or
signed-ranks testing was used for all continuous variables. All tests were 2-sided, with a P
value <0.05 considered statistically significant. Means are expressed as ± the SD. Medians
are presented for data not normally distributed.

Overall Status

Completed

Start Date

2011-09-19

Completion Date

2014-06-30

Primary Completion Date

2014-06-30

Phase

N/A

Study Type

Observational

Primary Outcome

Measure

Time Frame

first-trimester serum blys level
up to 13 weeks of pregnancy (first trimester)
second-trimester serum blys level
from 14 through 26 weeks of pregnancy (second trimester)
third-trimester serum blys level
from 27 weeks of pregnancy through delivery of baby (third trimester of pregnancy)
cord blood serum blys level
delivery of baby
post-partum serum blys level
1-2 days post-partum

Number Of Groups

2

Enrollment

222

Condition


Intervention

Intervention Type

Other

Intervention Name


Arm Group Label

pregnant

non-pregnant



Eligibility

Study Pop

Pregnant women seen at a single medical center

Sampling Method

Non-Probability Sample

Criteria

Inclusion Criteria:

- Adult woman

Exclusion Criteria:

- Unable to give informed consent

Gender

Female

Minimum Age

N/A

Maximum Age

N/A

Healthy Volunteers

No


Verification Date

2017-11-01

Lastchanged Date

2017-11-30

Firstreceived Date

2017-10-16

Responsible Party

Responsible Party Type

Principal Investigator

Investigator Affiliation

University of Southern California

Investigator Full Name

William Stohl

Investigator Title

Professor of Medicine


Has Expanded Access

No

Arm Group

Arm Group Label

pregnant

Description

Pregnant women receiving routine medical care, including venipuncture.


Arm Group Label

non-pregnant

Description

Women not pregnant receiving routine medical care, including venipuncture.



Firstreceived Results Date

N/A

Biospec Retention

Samples Without DNA

Biospec Descr

Banked sera.

Firstreceived Results Disposition Date

N/A

Study Design Info

Observational Model

Cohort

Time Perspective

Prospective


Study First Submitted

October 16, 2017

Study First Submitted Qc

November 30, 2017

Study First Posted

December 6, 2017

Last Update Submitted

November 30, 2017

Last Update Submitted Qc

November 30, 2017

Last Update Posted

December 6, 2017


ClinicalTrials.gov processed this data on December 06, 2017

Conditions

Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov, conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions

Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied. Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase

Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions that study is seeking to answer:

In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.

These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.



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