Clinical trial NCT02768818: Modulation of the Intestinal Flora With the Probiotic VIVOMIXX™ in Pregnant Women at Risk of Metabolic Complications
Official title: Modulation of the Intestinal Flora With the Probiotic VIVOMIXX™ in Pregnant Women at Risk of Metabolic Complications
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Gestational Diabetes Mellitus in Pregnancy, Diet- Controlled
Exercise Addiction
High-Risk Pregnancy
Dietary Modification
Keywords: Maternal Obesity Complicating Pregnancy
Lead sponsor: University of Modena and Reggio Emilia
Sponsor class: OTHER
First posted: 2016-05-11
Enrollment: 205
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The investigators aimed at evaluating the effectiveness of probiotics ingestion in changing maternal microbiota and preventing gestational diabetes in overweight and obese women.

To achieve these goals, obese (BMI\> 30 kg/m\^2) or overweight (BMI\> 25 kg/m\^2) pregnant women with risk factors were enrolled in the study and randomized to the supplementation with the probiotic VIVOMIXX® or with placebo.

The endpoints of this study are to evaluate if the dietary supplementation with the probiotic VIVOMIXX® modifies the maternal fecal microbiota (bifidobacteria and lactobacilli) and related enzymatic activity (alkaline sphingomyelinase and alkaline phosphatase), and if this if this is linked to an improvement of the intermediate metabolism (positive Oral Glucose Tolerance Test at 24-26 weeks).

Detailed description: This is a prospective, multicenter, randomized, double-blind, placebo-controlled trial.

208 pregnant women from the recruiting centers will be enrolled as follow: Women eligible to participate, prior informed consent, will be randomized to 2 capsules twice daily before breakfast and before dinner from randomization until delivery. The boxes will be given to the patients coded and blinded to investigators and participants, and will contain either the active ingredient (VIVOMIXX®, a mixture of 112 billion of eight strains for each capsule, namely Streptococcus thermophilus, bifidobacteria (B. breve, B. longum, B. infantis) and lactobacilli (L. paracasei, L. acidophilus, L. delbrueckii subsp bulgaricus, L. plantarum) or placebo.

The protocol includes a screening visit (Visit 1) at 10-12 weeks, two visits during pregnancy (at 26-28 weeks= Visit 2, and at 36-38 weeks=Visit 3) and a postnatal visit (2-3 days after delivery=Visit 4).

Eligible women should take two capsules twice daily (2 in the morning and 2 in the evening). Patients will be randomly assigned to the control or the VIVOMIXX® group.

The study agent VIVOMIXX® as well as the placebo will be supplied by "Mendes SA" for the whole study period.

During Visit 1 (at 10-12 weeks) written consent will be obtained, after information on expected benefits and possible inconveniences related to participation in the trial. Furthermore, eligible women will be asked to complete two questionnaires, one on dietary habits and one on gastrointestinal symptoms. The questionnaire on gastrointestinal symptoms will be submitted to the patients at each visit.

Height will be assessed at Visit 1, while the following parameters will be measured at each visit: weight, waits/hip circumference ratio, arterial blood pressure, plasma hemoglobin (Hb), hematocrit (Ht), fasting glycemia, fasting insulin and fasting glycated hemoglobin (HbA1c1).

A blood sample for the evaluation of homocysteine will be taken as well as urine and a faeces sample will be collected for nuclear-magnetic-resonance (NMR)-based metabolomics and intestinal microbiota analysis.

Furthermore, an Arm-band will be positioned for monitoring sleep and physical activities for one week at each visit.

At Visit 2 and 3 data regarding ultrasound examinations (Amniotic fluid index, abdominal circumference, cephalic circumference ratio) will be also collected.

Two-three days after delivery (Visit 4) data regarding the delivery (mode of delivery, gestational age at delivery) as well as the newborn (Apgar score, glycemia and serum bilirubin) were collected.

Moreover, a sample of colostrum (for NMR-based metabolomics, microbiota and high performance liquid chromatography-mass spectrometry -HPLC/MS- of vitamins analysis) and newborn faeces (for NMR-based metabolomics and microbiota analysis) sample will be collected.

Eligibility criteria: Inclusion Criteria:

* Women aged between 20 and 40 with singleton pregnancies and BMI at recruitment \> 30 kg/m\^2 or a BMI\> 25 kg/m\^2 and the simultaneous presence of at least 1 of the following risk factors: age\> 35 years, previous fetal macrosomia (\> 4500gr), family history of diabetes (first-degree relative with type 2 diabetes mellitus), previous gestational diabetes mellitus.
* Adherence to lifestyle prescription including dietary counselling and physical activity stimulation

Exclusion Criteria:

* Subjects who require intervention in addition to the lifestyle changes women with diet and habits much different from the Mediterranean area (Central Africa, Asian, etc..). In such subgroup it will be difficult to obtain adherence to diet prescription since their cultural attitudes and dietary habits.
* Pre-pregnancy BMI\> 40 kg/m\^2
* Chronic hypertension
* Fasting glycemia in the first trimester of\> 126 mg / dl or random glycemia \> 200 mg/dl

Primary outcomes:
measure: Maternal and newborn fecal microbiota changes (bifidobacteria and lactobacilli) and related enzymatic activity (alkaline sphingomyelinase and alkaline phosphatase) modifications
timeFrame: At baseline, at 24-26 week, at 36-38 week, 2-3 days after delivery
measure: Glucose metabolism changes
timeFrame: At 24-26 week
Secondary outcomes:
measure: Weight changes
timeFrame: At baseline, at 24-26 week, at 36-38 week, 2-3 days after delivery
measure: Maternal BMI
timeFrame: At baseline, at 24-26 week, at 36-38 week, 2-3 days after delivery
measure: Waist/hip circumference ratio
timeFrame: At baseline, at 24-26 week, at 36-38 week, 2-3 days after delivery
measure: Gestational weight gain
timeFrame: At baseline, at 24-26 week, at 36-38 week, 2-3 days after delivery
measure: HOMA Index
timeFrame: At baseline, at 24-26 week, at 36-38 week, 2-3 days after delivery
measure: HbA1c1
timeFrame: At baseline, at 24-26 week, at 36-38 week, 2-3 days after delivery
measure: glycemia
timeFrame: At baseline, at 24-26 week, at 36-38 week, 2-3 days after delivery
measure: insulinemia
timeFrame: At baseline, at 24-26 week, at 36-38 week, 2-3 days after delivery
measure: homocysteine plasmatic levels
timeFrame: At baseline, at 24-26 week, at 36-38 week, 2-3 days after delivery
measure: Requirement for insulin therapy
timeFrame: At baseline, at 24-26 week, at 36-38 week, 2-3 days after delivery
measure: Requirement for insulin therapy
timeFrame: At baseline, at 24-26 week, at 36-38 week, 2-3 days after delivery
measure: Quality of sleep
timeFrame: At baseline, at 24-26 week, at 36-38 week, 2-3 days after delivery
measure: Duration of sleep
timeFrame: At baseline, at 24-26 week, at 36-38 week, 2-3 days after delivery
measure: Onset of hypertension / preeclampsia
timeFrame: At delivery
measure: Time of delivery
timeFrame: At delivery
measure: Mode of delivery
timeFrame: At delivery
measure: Complications during delivery
timeFrame: At delivery
measure: Apgar score
timeFrame: Within 1 hour after delivery
measure: Newborn's weight
timeFrame: Within 1 hour after delivery
measure: Newborn's sex
timeFrame: Within 1 hour after delivery
measure: Newborn's abdomen / head ratio
timeFrame: 2-3 days after delivery
measure: Newborn's skinfold thickness at birth
timeFrame: 2-3 days after delivery
measure: Neonatal hypoglycemia
timeFrame: Within 24 hours from delivery
measure: Neonatal bilirubinemia
timeFrame: At delivery, 2-3 days after delivery
measure: Neonatal complications
timeFrame: 2-3 days after delivery
measure: Admission to Neonatal Intensive Care Unit (NICU)
timeFrame: Within 24 hours after delivery
measure: Admission to Neonatal Intensive Care Unit (NICU)
timeFrame: Within 24 hours after delivery
Other outcomes:
Locations:
city: Modena
country: Italy
facility: Mother-Infant Department, University of Modena and Reggio Emilia, Italy
Study officials:
References: