Clinical trial NCT06700044: Probiotic Supplementation During Pregnancy in Women With High-Risk Pregnancies
Official title: Assessing the Effects of Probiotic Supplementation in Women With High-Risk Pregnancies: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Preeclampsia
Gut Dysbiosis
Keywords: preeclampsia
probiotics
microbiome
lactobacillus
pregnancy
GutMagnific
Lead sponsor: Region Skane
Sponsor class: OTHER
Collaborators: name: ImmuneBiotech Medical Sweden AB
First posted: 2024-11-21
Enrollment: 150
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Preeclampsia (PE) is a complication during pregnancy characterized by hypertension, organ damage, and inflammation, without an effective treatment. The underlying mechanisms causing the disease also remain partly unknown. In this double-blind placebo-controlled study, the effects of probiotic dietary supplement GutMagnific during pregnancy will be assessed in pregnancies with a high risk of PE as well as low risk. The hypothesis is that probiotic dietary supplement GutMagnific can prevent or reduce the inflammatory response and clinical manifestations associated with PE through counteracting imbalances in the oral and gut microbiome composition.

Detailed description: PE is a leading cause of maternal and fetal morbidity and mortality worldwide, affecting 3-7% of pregnant women. PE is characterized by hypertension and organ damage manifesting after 20 gestational weeks, and is associated with an increased systemic inflammatory response in the mother. The clinical manifestations may vary greatly and are often more severe in early-onset PE (onset \<34 gestational weeks) than late-onset PE (onset ≥34 gestational weeks). Severe features include blood-pressure ≥160/110 mmHg, severe organ dysfunction, stroke, and eclampsia. Placental failure is central in the pathophysiology of PE, although the underlying mechanisms causing the disease remain partly unknown. Current research, including a previous study conducted by the investigators, suggests that disturbances in the gut microbiome might be involved in the pathogenesis of PE, leading to a dysfunctional immune response and damaged gut barrier functions. The investigators' previous study also indicated that PE is associated with gastrointestinal symptoms.

GutMagnific is an evidence-based probiotic dietary supplement, shown to be effective in correcting disturbances in the gut microbiome, reduce inflammation and repair a damaged gut barrier. It was originally developed for treatment of irritable bowel syndrome (IBS). There is an overlap in immunological responses involved in PE and IBS, and women with IBS have a higher risk of developing PE. Therefore, the investigators expect that the product might also have positive effects in pregnant women with a high risk of PE.

Eligibility criteria: Inclusion Criteria:

* Pregnant women ≥ 18 years old
* High risk of PE (≥ 1 high-risk factor, or ≥3 moderate risk factors according to the Swedish Society of Obstetrics and Gynecology (SFOG) 2019 guidelines); or low risk of PE (no high-risk factors, or \&lt;3 moderate risk factors):

  * High risk factors are:

    * Auto-immune diseases such as SLE or anti-phospholipid syndrome
    * Previous preeclampsia or eclampsia
    * Previous hypertension of pregnancy with preterm birth before gestational week 34, growth restriction, intrauterine fetal death or ablatio
    * Type 1 or 2 diabetes
    * Duplex (or triplex) pregnancy
    * Kidney disease
    * Chronic hypertension
    * IVF with egg donation
  * Moderate risk factors are:

    * Nulliparity
    * Heredity for preeclampsia (at least one of mother, maternal grandmother, or sister)
    * BMI\&gt;30
    * Age\&gt;40
    * Pregnancy interval \&gt;10 years
    * Systolic blood pressure \&gt;130 mmHg or diastolic blood pressure \&gt; 80 mmHg at admission in antenatal maternity care
    * African descent
    * Verified obstructive sleep apnea
* Ability to give written informed consent

Exclusion Criteria:

* Enrollment in another clinical study
* Use of other probiotic supplements in the last 2 weeks before baseline, or during the course of the study
* Use of antibiotics in the last 6 weeks
* Current treatment with metformin, progesterone, or regular medical treatment which may impact study aim (e.g. laxatives)
* Immunosuppression
* Diabetes mellitus (type I and type II)
* Inflammatory bowel disease
* Celiac disease
* Bad obstetric history
* Other serious conditions that might affect gut flora or capability of the subject to participate
* Language difficulties or difficulties understanding informed consent

Primary outcomes:
measure: Changes in oral and gut microbiota composition
timeFrame: Around gestational week 12 (baseline), 28, 37, and 6-8 weeks postpartum. In the event of a participant developing PE, samples will be taken at PE diagnosis as well.
Secondary outcomes:
measure: Changes in gastrointestinal symptoms
timeFrame: At the baseline and every two weeks until 6-8 weeks postpartum.
measure: Changes in blood pressure
timeFrame: At the baseline and continuously every 2-3 weeks from gestational week 24 throughout the pregnancy, and 6-8 weeks postpartum.
measure: Differences in obstetric outcome
timeFrame: Data will be collected from the Swedish Pregnancy Register (Graviditetsregistret) and/or medical records through study completion, an average of 6 months for term pregnancies.
measure: Changes in oral glucose tolerance test results
timeFrame: Gestational week 28
measure: Changes in circulatory Short-chain fatty acids (SCFAs) levels
timeFrame: Around gestational week 12 (baseline), 28, 37, and 6-8 weeks postpartum. In the event of a participant developing PE, samples will be taken at PE diagnosis as well.
measure: Changes in circulatory Lipopolysaccharide (LPS) levels
timeFrame: Around gestational week 12 (baseline), 28, 37, and 6-8 weeks postpartum. In the event of a participant developing PE, samples will be taken at PE diagnosis as well.
measure: Changes in metabolic parameters
timeFrame: Around gestational week 12 (baseline), 28, 37, and 6-8 weeks postpartum. In the event of a participant developing PE, samples will be taken at PE diagnosis as well.
measure: Change in systemic cytokine levels
timeFrame: Around gestational week 12 (baseline), 28, 37, and 6-8 weeks postpartum. In the event of a participant developing PE, samples will be taken at PE diagnosis as well.
Other outcomes:
Locations:
city: Lund
country: Sweden
facility: Region Skåne
Study officials:
References: