Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03029546 |
| Other study ID # |
2015H0236 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
November 2015 |
| Est. completion date |
November 2019 |
Study information
| Verified date |
April 2021 |
| Source |
Ohio State University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The investigator's main objective is to analyze the effects of a routine prenatal care
screening tool (glucola test for gestational diabetes) on maternal inflammation through
assessment of maternal circulatory biomarkers and blood pressure. Improving knowledge about
routine prenatal care and how a variety of screening factors affect maternal physiology
allows the investigators to be educated and informed when caring for mothers with medical
co-morbidities.
- Determine if an acute glucose load (50g) is associated with an in-vivo and in-vitro
increase in the concentration of Advanced Glycation End Products (AGEP's) that, in turn,
can impact vascular endothelial reactivity and induce an acute increase in blood
pressure. Previous studies generated in the investigators' laboratory showed that
circulating soluble Receptor for Advanced Glycation End Products (sRAGE) and Tumor
Necrosis Factor (TNF)-a (mediator of acute inflammation) are considered markers of the
extent of maternal RAGE activation and/or systemic inflammation, respectively.
- Determine how an acute glucose load (50g) at the time of normal screening for
gestational diabetes induces an acute increase in the level of sRAGE and TNF-a. If the
investigators' hypothesis is confirmed, the investigators will have strong confirmation
of the involvement of glycation products and TNF-a in generating the acute negative
clinical symptoms of women experiencing a glucose tolerance test, such as headache,
nausea, sweating, and bloating.
Description:
A. Research Design Participants will be identified at the time of their prenatal care visit
(24-28 weeks GA). The investigators will ask permission for participation in the research
protocol. A waiver of HIPPA has been added to the protocol to explain the sources
investigators might use to screen for eligible subjects. The electronic medical records may
be accessed with a partial waiver to review the medical information that will make each
subject a candidate for the protocol. The subject will be instructed on the benefits of the
study for which the participant is eligible and that management will not be influenced by the
participant's decision to volunteer or not. If the patient agrees to participate, the
participant will be given the written consent to read. The participant will be asked if there
is understanding, if all has been explained, and if there are any questions the investigators
need to clarify. The informed consent will be obtained. No ads, flyers, website postings,
recruitment letters, or oral/written scripts will be involved for recruitment of patients.
Interventions:
1. Informed consent.
2. Collection of blood (5 cc or one teaspoon of whole blood) and urine (1/2 cup) specimens
prior to administration of the 50 gr. glucola test. This protocol will be presented in
this arm of the study to women (n=50) who have a clinically indicated 1 hour glucose
tolerance test to diagnose gestational diabetes.
3. Blood pressure measurements every 15 minutes for one hour.
4. Collection of a second blood (5 cc or one teaspoon of whole blood), and urine (1/2 cup)
specimen following administration of the 50 gr. glucola test. Collection of blood at
this time will be clinically indicated to test for abnormal clinical values that might
classify the patient as gestational diabetic.
5. In a separate group of women classified as healthy pregnant controls (n=50) the
investigators will obtain informed consent using a protocol similar to the one described
above.
6. Collection of a blood (5 cc or one teaspoon of whole blood), and urine (1/2 cup)
specimen will be performed prior to administration of the 50 cc of plain water.
7. Blood pressure measurements will be performed every 15 minutes for one hour.
d. Collection of a second blood (5 cc or one teaspoon of whole blood), and urine (1/2 cup)
sample will occur at the end of the hour.
B. Sample Participants will be enrolled based on the eligibility for a one hour GTT. Chart
reviews of the clinic schedules will be performed the week prior to identify the target
population for recruitment who are 24-28 weeks gestation in need of a diabetes screen.
50 pregnant women in the high risk clinic presenting for diabetes screen at a routine
prenatal visit will be recruited for enrollment. This population is at risk for subsequent
adverse pregnancy outcomes, and the investigators will evaluate if biomarkers, such as
advanced glycation end products, are affected following glucose loading for diabetes
screening.
50 healthy pregnant women in the general obstetric clinic at McCampbell Hall will be
recruited as controls to ingest a 50cc sample of water and undergo identical objective
measurements (blood pressure measurements and urine/ blood samples) as the glucose loading
subjects. Biomarker analysis will be compared with that of the glucose loading population.
These patients serving as controls will undergo the clinically indicated glucola screening at
another visit between 24-28 weeks gestation.
Exclusion criteria include:
1. Non-English-speaking subjects will be excluded due to inability to appropriately
consent.
2. Non-pregnant patients will be excluded since this is a study of maternal tissues and
pregnancy outcomes related to exposures in pregnancy.
3. Men will be excluded since this is a study that includes pregnant women only by nature
of the research.
4. Prisoners will be excluded to avoid any potential for coercion
5. Minors under 18 years of age will be excluded due to lack of ability to consent without
a legal guardian.
6. Patients with contra-indications to glucola testing for gestational diabetes screening
will be excluded, such as bariatric surgery, inflammatory bowel disease with partial
bowel resection, and other mal-absorptive conditions.
C. Measurement/ Instrumentation 50 pregnant patients who are 24 to 28 weeks gestation
undergoing routine screening for gestational diabetes using a 50g glucose load will be
recruited. Following enrollment, maternal blood and urine specimens will be obtained as
outlined above. Blood pressure will be recorded. For this type of study design each patient
will serve as the participant's own control. Additionally, 50 healthy pregnant patients will
be recruited to perform a test similar to the diabetes screen using water only to serve as
additional controls. Advanced Glycation End Products among other proteins will be analyzed
for each of the specimens.
Using standard immunoassay procedures available in our laboratory, the investigators will
perform in parallel proteomics analysis of urine and maternal blood in addition to placental
evaluation following delivery. Advanced Glycation End Products and TNF-A will be the focus,
but, by performing proteomics studies of the biological samples, the investigators hope to
discover other biomarkers and biological pathways that might be responsible for the clinical
manifestations of the test. The newly discovered key proteins and important regulatory
protein pathways can potentially be targeted to identify and treat diabetes and other medical
conditions in pregnancy.
D. Detailed Study Procedures Women will be recruited in the OSUMC High Risk or Low risk
Clinics, and Labor and Delivery. Clinical data for the study will be abstracted from the
subject's medical record.
Potential hazards are related to the risks of an additional blood draw outside of routine
prenatal care. These risks include bruising, discomfort or pain at the site, infection, or
fainting. The risks are perceived as minimal, but patients will be compensated for their time
and willingness to undergo the discomfort of this additional blood draw.
Subjects will be coded as numbers 1 to 100. In addition, specimens will be coded with a
letter code followed by numbers in consecutive number. The PI will create a computer
worksheet where the name and medical record of the subject is linked to the coded information
of the subject and to each of the coded specimen numbers. The computer desktop that holds the
worksheet with Public Health Information (PHI) has a disk encryption. One copy of the consent
form will be kept in a secured and locked cabinet in the PI's office which is also locked.
The subject's name will be kept separate from the results. No reports will be communicated
back to the subjects or included in their medical record, since they will not affect how
pregnancy, labor or their post-delivery care will be managed. Only the subject's doctor and
the researchers will know of the subject's participation in the study. No further public
disclosure of this information will be made.
E. Internal Validity
To avoid study bias, we have also employed the following:
1. Use of internal controls and an external control group
2. Use of consecutive enrolled patients
F. Data Analysis Statistical comparisons between groups will be performed using Student t or
Mann-Whitney test or Two-way repeated analysis of variance (ANOVA) followed by post hoc
Holm-Sidak tests as appropriate. Pearson product moment correlation will be used to estimate
association between variables. A p=<0.05 will be considered to indicate statistical
significance. Gestational age, weight of the fetus at the time of glucose tolerance test,
presence or absence of any of the medical complications of pregnancy, medication and
substance abuse history, and maternal demographic characteristics will be analyzed and the
subject of statistical comparison.
