Assessment of DHA On Reducing Early Preterm Birth (ADORE)

Assessment of DHA On Reducing Early Preterm Birth (ADORE Trial)

The purpose of this study is to determine if giving a larger amount of DHA than currently included in some prenatal supplements can reduce early preterm birth (birth before 34 weeks of pregnancy).

Study Overview

• Status: Completed
• Conditions: Preterm Birth
• Intervention / Treatment: Drug: Docosahexaenoic acid - 200mg/day; Other: Placebo; Drug: Docosahexaenoic acid - 800mg/day

Detailed Description

Docosahexaenoic acid (DHA) is a nutrient found in some fish and eggs and its intake in US diets is typically low. Because DHA is important for early brain development, it has recently been added to many prenatal supplements. The usual amount is around 200 mg/day. Participants in this study are guaranteed to receive at least 200 mg/day of DHA.

Almost 5 in 100 births in the US occur before 34 weeks of pregnancy. There is no way to predict which births will occur before 34 weeks. In an earlier study conducted at the University of Kansas Medical Center, women who received 600 mg DHA/day compared to no DHA had fewer births before 34 weeks of pregnancy with fewer complications of preterm birth.

This study is designed to compare standard care (200 mg/day of DHA) to a higher amount of DHA (1000 mg/day) to determine if the higher amount will reduce early preterm birth (birth before 34 weeks of pregnancy). Individual participation in this study is expected last about 5 months.

• Study Type: Interventional
• Enrollment (Actual): 1100
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45220
      • University of Cincinnati
    • Columbus, Ohio, United States, 43210
      • Ohio State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Pregnant females 18 years and older 12 to 20 weeks gestation at study entry
• Agree to consume study capsules and a typical prenatal supplement of 200 mg DHA
• Available by telephone
• Able to speak and read in either English or Spanish language

Exclusion Criteria:

• Expecting multiple infants
• Gestational age at baseline <12 weeks or >20 weeks
• Unable or unwilling to agree to consume capsules until delivery
• Unwilling to discontinue use of another prenatal supplement that contains greater than or equal to 200 mg DHA per day
• Women with allergy to any component of DHA product (including algae), soybean oil or corn oil

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 200 mg/day DHA; Participants will receive 2 placebo pills/day that do not contain DHA. Like the experimental group, they will be given a supplement of Docosahexaenoic acid - 200mg/day , a common amount in prenatal vitamins.	Drug: Docosahexaenoic acid - 200mg/day; The control group will receive 1-capsule containing 200 mg DHA/d.; Other Names: DHA; Other: Placebo; Participants will receive 2 capsules (masked) containing half soybean oil and half corn oil equaling 800 mg.The soybean and corn oil combination does not contain DHA.
Experimental: 1000 mg/day DHA; The intervention includes Docosahexaenoic acid - 800mg/day per day provided in two 400 mg capsules. The intervention group as well as the active comparator group will be given 1-200 mg/capsule per day of DHA that is a common amount in prenatal vitamins.	Drug: Docosahexaenoic acid - 200mg/day; The control group will receive 1-capsule containing 200 mg DHA/d.; Other Names: DHA; Drug: Docosahexaenoic acid - 800mg/day; All participants will take 1000 mg/DHA per day (1 capsule will be labeled with 200 mg; 2 capsules will be masked with 400 mg each); Other Names: DHA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of Early Preterm Birth (<34 weeks gestation)	Bayesian posterior mean and 95% credible interval of pregnancies which result in an early preterm birth (birth before 34 weeks of pregnancy) by DHA dose	Baseline to 34 Weeks
Occurrence of Early Preterm Birth (<34 weeks gestation)	Bayesian posterior mean and 95% credible interval of pregnancies which result in an early preterm birth (birth before 34 weeks of pregnancy) by DHA dose and DHA status at enrollment (low/high) (modified statistical analysis plan while study was underway)	Baseline to 34 weeks
Maternal and infant adverse and serious adverse events	Bayesian posterior mean and 95% credible interval by dose	Enrollment to 30 days past last birth

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Very low birth weight	Bayesian posterior mean and 95% credible interval <1500 grams by dose	At birth
Low birth weight	Bayesian posterior mean and 95% credible interval <2500 grams by dose	birth
Maternal and infant DHA status	Bayesian posterior mean and 95% credible interval red blood cell phospholipid DHA (weight percent of total fatty acids) at enrollment and birth by dose	birth
Gestational age	Bayesian posterior mean and 95% credible interval weeks gestation at birth by dose	birth
Birth weight	Bayesian posterior mean and 95% credible interval in grams by dose	birth
Length and head circumference	Bayesian posterior mean and 95% credible interval in centimeters by dose	birth
Preterm birth (<37 weeks)	Bayesian posterior mean and 95% credible interval in weeks by dose	birth
Preterm birth (<37 weeks)	Number of pregnancies ending in preterm birth by dose	birth
Pre-eclampsia	Bayesian posterior mean and 95% credible interval	12-20 weeks gestation through birth at an average of 40 weeks
Pre-eclampsia	Number of patients with pre-eclampsia by dose	12-20 weeks gestation through birth at an average of 40 weeks
Gestational diabetes	Bayesian posterior mean and 95% credible interval by dose	12-20 weeks gestation through birth at an average of 40 weeks
Gestational diabetes	Number of patients with gestational diabetes by dose	12-20 weeks gestation through birth at an average of 40 weeks
Cesarean section	Bayesian posterior mean and 95% credible interval by dose	birth
Cesarean section	Number of patients with c-section by dose	birth
Spontaneous labor	Bayesian posterior mean and 95% credible interval by dose	birth
Spontaneous labor	Number of patients with spontaneous labor by dose	birth
Admissiion of neonate to a neonatal intensive care unit	Bayesian posterior mean and 95% credible interval by dose	birth
Admissiion of neonate to a neonatal intensive care unit	Number of neonates admited to a neonatal intensive care unit by dose	birth

Collaborators and Investigators

• Sponsor: University of Kansas Medical Center
• Collaborators: Ohio State University; Nationwide Children's Hospital; University of Cincinnati
• Investigators: Principal Investigator: Susan E. Carlson, PhD, University of Kansas Medical Center

Publications and helpful links

General Publications

• Mudaranthakam DP, Brown A, Kerling E, Carlson SE, Valentine CJ, Gajewski B. The Successful Synchronized Orchestration of an Investigator-Initiated Multicenter Trial Using a Clinical Trial Management System and Team Approach: Design and Utility Study. JMIR Form Res. 2021 Dec 22;5(12):e30368. doi: 10.2196/30368.
• Carlson SE, Gajewski BJ, Valentine CJ, Kerling EH, Weiner CP, Cackovic M, Buhimschi CS, Rogers LK, Sands SA, Brown AR, Mudaranthakam DP, Crawford SA, DeFranco EA. Higher dose docosahexaenoic acid supplementation during pregnancy and early preterm birth: A randomised, double-blind, adaptive-design superiority trial. EClinicalMedicine. 2021 May 17;36:100905. doi: 10.1016/j.eclinm.2021.100905. eCollection 2021 Jun.
• Carlson SE, Gajewski BJ, Valentine CJ, Rogers LK, Weiner CP, DeFranco EA, Buhimschi CS. Assessment of DHA on reducing early preterm birth: the ADORE randomized controlled trial protocol. BMC Pregnancy Childbirth. 2017 Feb 13;17(1):62. doi: 10.1186/s12884-017-1244-5.

Study record dates

Study Major Dates

• Study Start (Actual): June 8, 2016
• Primary Completion (Actual): October 5, 2020
• Study Completion (Actual): October 5, 2020

Study Registration Dates

• First Submitted: December 8, 2015
• First Submitted That Met QC Criteria: December 8, 2015
• First Posted (Estimate): December 10, 2015

Study Record Updates

• Last Update Posted (Actual): March 30, 2021
• Last Update Submitted That Met QC Criteria: March 25, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Docosahexaenoic acid (DHA); Preterm birth; Low birth weight; Very low birth weight; Pregnancy outcome; Superiority trial; Adaptive design; Early preterm birth; Randomized cliinical trial
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth
• Other Study ID Numbers: STUDY00003455