Ignite Creation Date:
2024-05-06 @ 8:24 PM
Last Modification Date:
2024-10-26 @ 3:26 PM
Study NCT ID:
NCT06362356
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-04-18
First Post:
2024-04-08
Brief Title:
Microbial Metabolites and Outcomes of Pregnancy Study
Sponsor:
The Cleveland Clinic
Organization:
The Cleveland Clinic
Study Overview
Official Title:
Microbial Metabolites and Outcomes of Pregnancy Study
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
MMOPS
Brief Summary:
Emerging data connect diet the gut microbiota and its metabolites in cardiometabolic disease Hypertensive disorders of pregnancy HDP are common and are a leading cause of maternal and neonatal morbidity HDP likely share similar pathophysiology as cardiometabolic disease in non-pregnant people with a yet unrevealed role of diet and the gut microbiota including systemic inflammation and endothelial dysfunction
Despite high biological plausibility that nutrition the gut microbiota and its metabolites may play a role in health and disease in pregnancy there is a paucity of data regarding these associations thus limiting advancement of the field Similar to the proposed pathogenesis for diet gut microbiota and the microbial metabolite trimethylamine-N-oxide TMAO in cardiovascular disease we hypothesize that the interplay between maternal diet the gut microbiota and its associated microbial metabolites play a mechanistic role in HDP We propose to test this hypothesis in a racially-diverse US cohort to determine association with adverse pregnancy outcomes specifically future development of HDP We propose to prospectively collect plasma and urine TMAO throughout pregnancy from a cohort of 200 pregnant participants
Through 1 characterizing plasma and urine TMAO levels across each trimester of pregnancy and 2 assessment of this microbial metabolite as a predictor of development of HDP we have the potential to identify a biomarker that would allow us to identify people at risk of HDP early in pregnancy and provide new opportunities for therapeutic interventions to improve maternal and neonatal outcomes
Despite high biological plausibility that nutrition the gut microbiota and its metabolites may play a role in health and disease in pregnancy there is a paucity of data regarding these associations thus limiting advancement of the field Similar to the proposed pathogenesis for diet gut microbiota and the microbial metabolite trimethylamine-N-oxide TMAO in cardiovascular disease we hypothesize that the interplay between maternal diet the gut microbiota and its associated microbial metabolites play a mechanistic role in HDP We propose to test this hypothesis in a racially-diverse US cohort to determine association with adverse pregnancy outcomes specifically future development of HDP We propose to prospectively collect plasma and urine TMAO throughout pregnancy from a cohort of 200 pregnant participants
Through 1 characterizing plasma and urine TMAO levels across each trimester of pregnancy and 2 assessment of this microbial metabolite as a predictor of development of HDP we have the potential to identify a biomarker that would allow us to identify people at risk of HDP early in pregnancy and provide new opportunities for therapeutic interventions to improve maternal and neonatal outcomes
Detailed Description:
Overall Plan
To evaluate maternal markers of metabolism including the maternal microbial metabolite Trimethylamine N-oxide TMAO across pregnancy and its association with development of hypertensive disorders of pregnancy
Research Design and Methods
This prospective longitudinal cohort will enroll pregnant patients in their first trimester of pregnancy 10-14 weeks gestation Plasma serum blood ribonucleic acid RNA and urine samples will be collected at the time of enrollment along with dietary assessment and self-reported demographic information The total volume of blood for research lab purposes will be 225 cc one 10 ml lavender top tube one 10 ml serum separator tube and one 25 ml PAXgene blood RNA tube If research labs are drawn in coordination with other necessary prenatal labs the anticipated maximum volume at blood draw would be 42-50 cc of blood depending on combination of commonly ordered prenatal labs The total amount of blood drawn from pregnant subjects including clinical and research draws will not exceed 50ml in a two-week period Plasma serum blood RNA and urine samples will again be collected in the second trimester at 24-28 weeks In addition maternal plasma serum blood RNA and urine will be collected at the time of delivery admission A 10 cc sample of cord blood will be obtained after delivery and the placenta will be sent to pathology for evaluation The investigators will measure TMAO levels and other markers of metabolism on all three maternal samples and that of the cord blood Deoxyribonucleic acid DNA from the buffy coat of plasma collection and RNA from a PAXgene blood tube will be obtained for molecular testing of metabolic biomarkers The placenta will be examined pathologically with attention to vascular pathology In addition a dietary history will be obtained at each time point using the interviewer-guided ASA24 Automated self-administered 24-hour dietary assessment tool-a web-based survey provided at no cost through the National Institutes of Health website under a researcher-only password protected account httpsepigrantscancergovasa24
Data and Sample Collection
Phlebotomy and midstream urine self-collection will be performed at pre-specified time points 10-14 weeks 24-28 weeks and at time of admission for delivery Placenta and cord blood samples will be collected following delivery by delivering clinician
Data and Sample Storage
Data security will be ensured by limiting access to those team members involved in the collection and analysis of patient data Medical record data will be stored securely through Cleveland Clinic REDCap database Dietary assessment data will be similarly stored within the web-based NIH Automated Self-Administered 24-hour ASA24 Dietary Assessment Tool researcher password-protected account Safety monitoring will include ensuring safe and clean clinical environment for specimen collection following appropriate safety protocol for venipuncture and proper disposal of supplies in designated clinical areas
Sample Size
Since the investigators have limited information regarding TMAO in pregnancy the power calculation was estimated to detect mean TMAO differences between groups using a two sample T-test at a significance level of 005 80 power and total sample size of 200 patients with 10 dropout rate Standard deviations of TMAO estimated from the literature are ranging from 061 to 1015 micromoleL assuming the ratio of hypertensive disorders of pregnancy group to normal group is 110 the detectable mean TMAO differences were calculated to be 0451 to 7497 micromoleL
Analysis plan
Patients with hypertensive disorders of pregnancy will be compared to those without Approximately normally-distributed continuous measures will be summarized using means and standard deviations and will be compared using two-sample t-tests Continuous measures that show departure from normality and ordinal measures will be summarized using medians and quartiles and will be compared using Wilcoxon rank sum tests Categorical factors will be summarized using frequencies and percentages and will be compared using Pearsons chi-square tests or Fishers Exact tests If groups differ on baseline characteristics linear regression adjusting for factors of clinical importance will be performed Depending on the distribution of final data Pearson or Spearman correlation will be calculated between TMAO level and other continuous variables For each level of categorical factors TMAO level will be summarized using mean and standard deviation or median and quartiles and will be compared using analysis of variance ANOVA or Kruskal-Wallis tests All analyses will be done using SAS version 94 The SAS Institute Cary NC and a p 005 will be considered statistically significant
To evaluate maternal markers of metabolism including the maternal microbial metabolite Trimethylamine N-oxide TMAO across pregnancy and its association with development of hypertensive disorders of pregnancy
Research Design and Methods
This prospective longitudinal cohort will enroll pregnant patients in their first trimester of pregnancy 10-14 weeks gestation Plasma serum blood ribonucleic acid RNA and urine samples will be collected at the time of enrollment along with dietary assessment and self-reported demographic information The total volume of blood for research lab purposes will be 225 cc one 10 ml lavender top tube one 10 ml serum separator tube and one 25 ml PAXgene blood RNA tube If research labs are drawn in coordination with other necessary prenatal labs the anticipated maximum volume at blood draw would be 42-50 cc of blood depending on combination of commonly ordered prenatal labs The total amount of blood drawn from pregnant subjects including clinical and research draws will not exceed 50ml in a two-week period Plasma serum blood RNA and urine samples will again be collected in the second trimester at 24-28 weeks In addition maternal plasma serum blood RNA and urine will be collected at the time of delivery admission A 10 cc sample of cord blood will be obtained after delivery and the placenta will be sent to pathology for evaluation The investigators will measure TMAO levels and other markers of metabolism on all three maternal samples and that of the cord blood Deoxyribonucleic acid DNA from the buffy coat of plasma collection and RNA from a PAXgene blood tube will be obtained for molecular testing of metabolic biomarkers The placenta will be examined pathologically with attention to vascular pathology In addition a dietary history will be obtained at each time point using the interviewer-guided ASA24 Automated self-administered 24-hour dietary assessment tool-a web-based survey provided at no cost through the National Institutes of Health website under a researcher-only password protected account httpsepigrantscancergovasa24
Data and Sample Collection
Phlebotomy and midstream urine self-collection will be performed at pre-specified time points 10-14 weeks 24-28 weeks and at time of admission for delivery Placenta and cord blood samples will be collected following delivery by delivering clinician
Data and Sample Storage
Data security will be ensured by limiting access to those team members involved in the collection and analysis of patient data Medical record data will be stored securely through Cleveland Clinic REDCap database Dietary assessment data will be similarly stored within the web-based NIH Automated Self-Administered 24-hour ASA24 Dietary Assessment Tool researcher password-protected account Safety monitoring will include ensuring safe and clean clinical environment for specimen collection following appropriate safety protocol for venipuncture and proper disposal of supplies in designated clinical areas
Sample Size
Since the investigators have limited information regarding TMAO in pregnancy the power calculation was estimated to detect mean TMAO differences between groups using a two sample T-test at a significance level of 005 80 power and total sample size of 200 patients with 10 dropout rate Standard deviations of TMAO estimated from the literature are ranging from 061 to 1015 micromoleL assuming the ratio of hypertensive disorders of pregnancy group to normal group is 110 the detectable mean TMAO differences were calculated to be 0451 to 7497 micromoleL
Analysis plan
Patients with hypertensive disorders of pregnancy will be compared to those without Approximately normally-distributed continuous measures will be summarized using means and standard deviations and will be compared using two-sample t-tests Continuous measures that show departure from normality and ordinal measures will be summarized using medians and quartiles and will be compared using Wilcoxon rank sum tests Categorical factors will be summarized using frequencies and percentages and will be compared using Pearsons chi-square tests or Fishers Exact tests If groups differ on baseline characteristics linear regression adjusting for factors of clinical importance will be performed Depending on the distribution of final data Pearson or Spearman correlation will be calculated between TMAO level and other continuous variables For each level of categorical factors TMAO level will be summarized using mean and standard deviation or median and quartiles and will be compared using analysis of variance ANOVA or Kruskal-Wallis tests All analyses will be done using SAS version 94 The SAS Institute Cary NC and a p 005 will be considered statistically significant
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None