Vascular Inflammation and Anti-inflammatory Supplements After Adverse Pregnancy Outcomes (VIA)

Supplements to Improve Vascular Inflammation After an Adverse Pregnancy Outcome

Women who had an adverse pregnancy outcome (APO), such as preeclampsia, preterm birth, or gestational diabetes, have a higher risk for heart disease. Some of the extra risk for heart disease after APOs is thought to be caused by inflammation. Investigators will randomize women who had an APO in the past 3 years to receive an anti-inflammatory supplement or serve as a time control. Investigators will compare blood pressure, arterial stiffness, blood vessel reactivity, and blood markers of inflammation between women who did and did not receive the supplement. Investigators will determine women's attitudes about taking a dietary supplement and measure whether the participants who receive the supplement take all or most of the doses.

Study Overview

• Status: Completed
• Conditions: Pre-Eclampsia; Intrauterine Growth Restriction; Hypertension in Pregnancy; Pre-Term
• Intervention / Treatment: Dietary supplement: Anti-inflammatory supplement

Detailed Description

Research Design. Investigators will invite 56 women with an APO within the past 3 yrs to participate. Women will be randomly assigned to the 4-wk intervention group (n=28) or a standard care group (n=28) using a computerized random number generator, stratified by race. Assuming up to 25% with poor adherence, Investigators expect that 42 women (21 each arm) will complete the study. No data exist related to effects of supplementation on vascular function in our population, we assumed a medium effect size, i.e. Cohen's d~0.50 and accepting a β=0.80, to generate sample sizes. Generation of effect sizes is a key outcome of this study. Investigators will conduct a vascular assessment and blood draw at two visits: before the intervention begins and within 3 days of completing the intervention. Investigators will conduct visits during the early follicular phase of menstrual cycle to account for fluctuating hormones. Vascular testing will be performed in the supine position and ≥4 hours after a light meal. Surveys for Aim 2 will be completed within the first 2 weeks of study enrollment, and interviews for Aim 2 will be conducted at the end of Visit 2.

Anti-inflammatory supplementation intervention. Participants randomized to the supplementation intervention will receive a commercially available supplement (100 mg curcumin phytosome, 100 mg quercetin phytosome, 100 mg green tea phytosome, 100 mg trans-resveratrol, 100 mg trans-pterostilbene). Participants will be asked to take 2 doses/day (1g total). Participants randomized to supplementation will receive a daily email reminding them to take the supplement. Covariates. Medical history, age, and sociodemographics will be obtained via self-report. Investigators will use validated surveys to determine physical activity, sedentary behavior, and smoking history. Height and weight will be measured.

Acceptability of Dietary Supplementation. Investigators will administer surveys to all participants to understand their perceptions of dietary supplementation, including potential benefits and consequences associated with supplementation. Investigators will determine willingness to use supplements, barriers to supplementation, and who, i.e., physician or partner, influences their decision to use dietary supplements.

Adherence and Barriers to Adherence. Investigators will count pills to determine adherence to supplementation regime. Investigators will assess each intervention participant's perceptions of supplementation with a brief interview at the final visit. Interviews will capture participant's perceptions of the role of supplementation for CVD prevention, and any side effects of supplementation. Investigators will ask participants to recommend ways to encourage participation and ask questions regarding their perceptions of the incentive structure and contact with the study team. Investigators will contact participants who drop out of the study to identify reasons for drop out.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Columbia, South Carolina, United States, 29208
      • Public Health Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Had a singleton pregnancy in the past 3 years that lasted 20 weeks or more
• Most recent pregnancy was complicated by an APO

Exclusion Criteria:

• currently pregnant or breastfeeding,
• current smoking,
• active cancer,
• regular use of NSAIDs, steroidal medications, statins, or other anti-inflammatory supplements,
• HIV/AIDS,
• uncontrolled high blood pressure ( >160/>110 mmHg),
• unwilling or unable to use a dietary supplement,
• known sensitivity to resveratrol, curcumin, green tea, or quercetin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Participants in this arm will receive a commercially available anti-inflammatory supplement.	Dietary supplement: Anti-inflammatory supplement; commercially available combination of curcumin, quercitin, resveratrol, and green tea
No Intervention: Control; Participants in this arm will not receive a commercially available anti-inflammatory supplement.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Pressure (mmHg)	Investigators will measure blood pressure in the arm and use applanation tonometry to estimate aortic blood pressure	1 month
Arterial Stiffness (m/s)	Arterial stiffness will be measured with pulse wave velocity using applanation tonometry and heart rate	1 month
Augmentation Index (%)	Applanation tonometry will be used to describe systolic blood pressure augmentation, a measure of arterial wave reflection intensity.	1 month
Endothelial Function (Reactive Hyperemia)	Venous occlusion plethysmography will be used to mease the change in forearm blood flow after a 5-min occlusion	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inflammatory Vascular Biomarkers (pg/dL)	concentrations of circulating adhesion molecules ICAM and VCAM	1 month
Acceptability of Intervention (Likert Scales From 1-5; Not Likely at All to Extremely Likely and Free Text Fields)	Surveys regarding opinion and likelihood of taking supplements. Here we report the number of participants who thought supplements were somewhat or extremely useful (Likert score of 4-5) for improving health.	1 month
Perception of Intervention (15-20 Minute Interview)	Interviews will be used to determine barriers and facilitators of adherence. We report number of participants who were happy with contact with study team for adherence reminders.	1 month

Collaborators and Investigators

• Sponsor: University of South Carolina
• Investigators: Principal Investigator: Abbi Lane-Cordova, PhD, University of South Carolina

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2020
• Primary Completion (Actual): June 30, 2021
• Study Completion (Actual): May 30, 2022

Study Registration Dates

• First Submitted: November 6, 2020
• First Submitted That Met QC Criteria: November 12, 2020
• First Posted (Actual): November 18, 2020

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 19, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: inflammation; vascular health; adverse pregnancy outcome
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Fetal Diseases; Pregnancy Complications; Growth Disorders; Hypertension; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Inflammation; Eclampsia; Pre-Eclampsia; Fetal Growth Retardation; Hypertension, Pregnancy-Induced; Anti-Inflammatory Agents
• Other Study ID Numbers: 10010335

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We will disseminate results at conferences and in medical journals. We are open to sharing limited datasets upon request.
• IPD Sharing Time Frame: Upon completion of the study

IPD Sharing Access Criteria

Contact the PI:

Abbi Lane-Cordova lanecord@mailbox.sc.edu 803-777-7568

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No