Omega-3 Fatty Acids for Smoking Cessation in Pregnancy

NCT04417595 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 200609R01HD098719
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

Smoking is the most important modifiable risk factor for adverse pregnancy outcomes including preterm birth, neonatal death, and maternal complications. Rates of smoking cessation during pregnancy are low, particularly in underserved populations, and currently approved pharmacotherapies for smoking cessation either are considered unsafe in pregnancy or have uncertain effectiveness. Identifying safe and effective interventions, which might mitigate the adverse effects of smoking on maternal-fetal outcomes, is a major public health priority. We hypothesize that smoking-induced n-3 LCPUFA relative deficiencies may be an important mechanism contributing to tobacco-related adverse pregnancy outcomes and that n-3 LCPUFA supplementation specifically targeted to pregnant smokers may reduce these complications. Support for this hypothesis comes from a recent secondary analysis of the Omega-3 Fatty Acids Supplementation to Prevent Preterm Birth trial that found that only smokers taking n-3 LCPUFAs had a reduction in preterm labor risk as compared to non-smokers. While compelling, this study was a post hoc analysis that included only a small sample of smokers and did not collect data on smoking behaviors during follow up. Yet the ascertainment of longitudinal smoking behavior is critical, as some clinical studies have found that supplemental n-3 LCPUFAs might also reduce nicotine cravings, and lower daily cigarette use. Thus, smokers may doubly benefit from replenishing n-3 LCPUFAs via lower risk of preterm labor and/or increased smoking cessation. To address these knowledge gaps, we are proposing a multi-center, randomized, placebo-controlled, double-blinded study of n-3 LCPUFA supplementation in 400 pregnant smokers. We will collect detailed information on smoking behavior, validated biological markers of cigarette exposure (urinary cotinine, end-expiratory carbon monoxide) and biomarkers of n-3 LCPUFA status (red blood cell phospholipid membrane fatty acids). Our specific aims of this proposal are to 1) determine the effect of supplemental n-3 LCPUFAs on gestational age at delivery and preterm labor in pregnant smokers and 2) determine the effect of n-3 LCPUFA supplementation on tobacco use in pregnant smokers. We will recruit potential participants from eight obstetrics clinics across the Middle-Tennessee area. Our study could have a major translational impact on both adverse tobacco-related birth outcomes and smoking cessation efforts.

Conditions

Preterm Labor; Tobacco Use Disorder

Outcome Measures

Primary Outcomes (2)

• Gestational age at delivery

  Gestational age at randomization will be determined on the basis of the last menstrual period and earliest ultrasound examination and will not be revised after being assigned a study group. Gestational age will be estimated from the last menstrual period (LMP) and adjusted for the first-trimester ultrasound. If a self-reported LMP is greater than 7 days from the calculated ultrasound LMP, the ultrasound will be used to assign gestational age.

  At delivery

• Change in cigarettes per day

  Percentage change from baseline in cigarettes per day (CPD) at 12 weeks. The outcome will be determined based on participant self-report.

  At 12 weeks

Secondary Outcomes (12)

• Percent of neonates with fetal death and still birth

  At delivery

• Individualized birth weight Z-score (adjusted for gestational age and maternal weight)

  At delivery

• Apgar score

  At delivery

• Percent of neonates with intraventricular hemorrhage

  At delivery

• Percent of neonates with neonatal enterocolitis

  At delivery

Study Arms (2)

Fish Oil

EXPERIMENTAL

Participants allocated to n-3 LCPUFA supplementation will be instructed to take four 1000 mg n-3 LCPUFA capsules (Metagenics™) daily. This will provide a total daily dose of 4000 mg n-3 LCPUFAs (2840 EPA and 1160 DHA).

Drug: Fish Oil (Containing Omega-3 Acids)

Olive Oil

PLACEBO COMPARATOR

Oleic acid (olive oil) capsules have a similar texture, size, color, and consistency to EPA capsules. Participant will be instructed to take four 100mg olive oil capsules

Drug: Olive Oil

Interventions

Fish Oil (Containing Omega-3 Acids) DRUG

Fish Oil Supplement

Also known as: Fish Oil

Fish Oil

Olive Oil DRUG

Olive Oil Supplement

Also known as: Placebo

Olive Oil

Eligibility Criteria

• Age: 16 Years - 40 Years
• Gender Eligibility Details: Actively pregnant
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• ≥ 16 or ≤ 40 years of age
• Currently reporting daily cigarette use (≥ 1 CPD; reporting 10 or more CPD prior to pregnancy)
• Between 12 and 24 weeks gestation
• An exhaled carbon monoxide reading of at least 8 ppm
• A cell phone or land line that can be reached directly

You may not qualify if:

• Allergy to fish; currently using fish oil supplements
• Active substance abuse (not including supervised buprenorphine use)
• Unable to give consent or obtain assent for minors
• Known fetal abnormality
• Chronic hypertension
• Seizure disorder
• Clotting disorder
• White's classification D or higher diabetes
• Planned cerclage
• Plan move from the Middle-Tennessee area within the next 9-months
• Insufficient time to perform the complete enrollment process
• Barrier to communication (e.g., low English proficiency or hearing/speech impairment)

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (1)

• Murff HJ, Greevy RA, Sanghani RS, Hartmann KE, Hartert TV, Graves CR, Lee SS, Tindle HA. Investigating N-3 Fatty Acids to prevent Neonatal Tobacco-related outcomeS (INFANTS): study protocol for a double-blind, randomized, placebo-controlled parallel clinical trial of n-3 polyunsaturated fatty acids in pregnant smokers. Trials. 2021 Dec 14;22(1):922. doi: 10.1186/s13063-021-05865-7.

  PMID: 34906201 DERIVED

MeSH Terms

Conditions

Obstetric Labor, Premature; Tobacco Use Disorder

Interventions

Fish Oils; Olive Oil

Condition Hierarchy (Ancestors)

Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Oils; Lipids; Dietary Fats, Unsaturated; Dietary Fats; Fats; Fats, Unsaturated; Plant Oils; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Placebo controlled
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Randomizes, parallel arm, double-blind, placebo controlled clinical trial

Study Record Dates

• First Submitted: May 29, 2020
• First Posted: June 4, 2020
• Study Start: November 10, 2020
• Primary Completion: November 30, 2024
• Study Completion: January 8, 2026
• Last Updated: December 15, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)