Synbiotics in Patients at RIsk fOr Preterm Birth

NCT05966649 | Recruiting DMC

• 1 other identifier: Z-2022080
• Study Type: interventional
• Target: 402
• Locations: 1 country
• Sites: 9

Brief Summary

Prematurity remains the main cause of death and serious health problems in new-borns. Besides the need for hospitalization and medical interventions in the first weeks or months of the new-borns' life, prematurity can cause long-lasting health problems (e.g. multiple hospital admissions, developmental delay, learning difficulties, motor delay, hearing or eye problems, ...). Moreover, prematurity places an enormous economic burden on the society. Aside from the medical problems and the financial cost, the emotional stress and psychological impact on the parents, siblings and other family members should not be underestimated. Previous preterm delivery (before 37 weeks of pregnancy) increases the risk for recurrent preterm delivery in a subsequent pregnancy. Therefore, these women should be considered as 'high risk' for preterm birth. Infections ascending from the vagina may be an important cause of preterm delivery in certain cases. Some women have an abnormal vaginal microbiome and are therefore at risk for infections and preterm birth. On the other hand, the vaginal flora is more stable and resistant to infections in healthy pregnant women who deliver at term (after 37 weeks of gestation). Synbiotics are a mixture containing probiotics and prebiotics. Probiotics are living bacteria with potential beneficial effects that can be used safely in pregnancy, while prebiotics are consumed by the bacteria. It is known that probiotics, when used for a long period of time, can maintain a healthy and stable vaginal flora that may protect against infections. In this study, pregnant patients with a history of preterm birth will be included in the first trimester of pregnancy to start with synbiotics or placebo. The investigators will examine the effect of synbiotics on the vaginal flora and on the pregnancy duration. The hypothesis is that synbiotics, when started early in the pregnancy, can change the disturbed vaginal flora into a stable micro-environment.

Conditions

Preterm Spontaneous Labor With Preterm Delivery; Preterm Birth; Microbial Colonization; Microbiome Dysbiosis; Vaginal Microbiome; Synbiotics

Keywords

Preterm birth; Vaginal microbiome; Probiotics; Synbiotics

Outcome Measures

Primary Outcomes (1)

• Gestational age at delivery

  Through study completion - at delivery

Secondary Outcomes (19)

• Incidence of PTB, defined as GA at delivery < 37 weeks

  Through study completion - at delivery

• Proportion of PTB in different categories

  Through study completion - at delivery

• PPROM

  Up to 34 weeks from the date of randomization

• PPROM

  Up to 34 weeks from the date of randomization

• PPROM

  Up to 34 weeks from the date of randomization

Other Outcomes (3)

• Effect of antibiotics on the vaginal microbiome

  During pregnancy until 28 days after PPROM

• Effect on the gastrointestinal microbiome of the neonate in case of PPROM

  Between 13 to 36 weeks from the date of randomization

• Placental microbiome in case of preterm birth

  Between 13 to 36 weeks from the date of randomization

Study Arms (2)

Synbiotics

EXPERIMENTAL

Oral synbiotic (food supplement) containing 8 probiotic Lactobacillus strains, the prebiotics inulin, fructooligosaccharides (FOS) and D-mannose.

Other: Synbiotics

Placebo

PLACEBO COMPARATOR

Matching placebo

Other: Placebo

Interventions

Synbiotics OTHER

Oral synbiotic (food supplement) containing 8 probiotic Lactobacillus strains, the prebiotics inulin, fructooligosaccharides (FOS) and D-mannose.

Synbiotics

Placebo OTHER

Matching placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent must be obtained before any study assessment is performed;
• years of age or older;
• Singleton pregnancy;
• Pregnancy consultation between 8 and 10 weeks gestation.
• At least one of the following risk factors for spontaneous preterm birth:
• Prior spontaneous preterm birth, defined as delivery between 24 and 36 weeks following PPROM, preterm labor or cervical insufficiency
• PPROM ≤36 weeks in previous pregnancy
• Prior spontaneous second-trimester pregnancy loss, defined as PPROM, preterm labor or cervical insufficiency with birth between 14 and 24 weeks.

You may not qualify if:

• Patients who are already using pro-, pre- or synbiotics and not willing to stop
• Multiple pregnancy
• Need for primary (type 1) cerclage
• Inflammatory bowel disease
• Known congenital uterine anomaly
• History of LLETZ conization

Sponsors & Collaborators

• Ziekenhuis Oost-Limburg: lead
• Federaal Kenniscentrum voor Gezondheidszorg, Belgium: collaborator

Study Sites (9)

Universitaire Ziekenhuis Antwerpen

Edegem, Antwerpen, 2650, Belgium

RECRUITING

Ziekenhuis Oost-Limburg

Genk, Limburg, 3600, Belgium

RECRUITING

Universitaire Ziekenhuizen Leuven

Leuven, Limburg, 3000, Belgium

RECRUITING

CHR Citadelle

Liège, Liège, 4000, Belgium

RECRUITING

UZ Gent

Ghent, Oost-Vlaanderen, 9000, Belgium

RECRUITING

AZ Sint-Jan

Bruges, West-Vlaanderen, 8300, Belgium

RECRUITING

AZ Sint-Lucas

Bruges, West-Vlaanderen, 8310, Belgium

RECRUITING

AZ Maria Middelares

Ghent, West-Vlaanderen, 9000, Belgium

RECRUITING

AZ Groeninge

Kortrijk, 8500, Belgium

RECRUITING

Related Publications (1)

• Nulens K, Papy E, Tartaglia K, Dehaene I, Logghe H, Van Keirsbilck J, Chantraine F, Masson V, Simoens E, Gysemans W, Bruckers L, Lebeer S, Allonsius CN, Oerlemans E, Steensels D, Reynders M, Timmerman D, Devlieger R, Van Holsbeke C. Synbiotics in patients at risk for spontaneous preterm birth: protocol for a multi-centre, double-blind, randomised placebo-controlled trial (PRIORI). Trials. 2024 Sep 17;25(1):615. doi: 10.1186/s13063-024-08444-8.

  PMID: 39289685 DERIVED

MeSH Terms

Conditions

Premature Birth; Communicable Diseases

Interventions

Synbiotics

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Prebiotics; Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Probiotics; Food and Beverages

Central Study Contacts

Caroline Van Holsbeke, PhD

CONTACT

003289804057; Caroline.van.holsbeke@zol.be

Katrien Nulens, MD

CONTACT

003289804125; Katrien_Nulens@hotmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2023
• First Posted: July 28, 2023
• Study Start: March 16, 2023
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): June 1, 2029
• Last Updated: February 27, 2026

Record last verified: 2026-02

Locations

BE (9)