The Effect of Oral Probiotics on Glycemic Control of Women With Gestational Diabetes Mellitus

Study Overview
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Brief Summary
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Scientific background: Uncontrolled gestational diabetes mellitus (GDM) is associated with severe maternal and neonatal morbidities. Treatment of GDM is multidisciplinary and includes lifestyle changes and medications. However, the efficacy of these treatments is limited due to poor motivation, daily painful blood tests and multiple injections. Probiotic supplements were shown to modulate the gut microbiome by reducing the adverse metabolic effects associated with pathogenic microbial colonization. Promising effects on glycemic control and insulin resistance in non-pregnant diabetic patients were reported. However, the effect of probiotics on glycemic control in GDM has not been elucidated. Objectives: To examine the effect of a mixture of probiotic strains given daily on maternal glycemic parameters, and pregnancy outcomes among women with GDM. Working hypothesis: Oral administration of probiotics will be effective in glucose control of patients with GDM and their neonates without causing significant adverse effects. Type of research and methods of data collection: A prospective randomized, double blind, placebo controlled trial. Women newly diagnosed with GDM will be recruited and followed in the GDM clinic and Maternal-Fetal Medicine ward (including the research clinic) at Emek Medical Center. They will be divided into a research group, receiving the probiotic formula Femina II and a control group, receiving a placebo (2 capsules/day) until delivery. Glycemic control will be evaluated by daily glucose charts. After 2 weeks of diet and probiotic/placebo treatment and thereafter, pharmacotherapy will be started in case of poor glycemic control according to the daily glucose charts. Blood tests for glycated molecules will be performed. Fetal well-being and growth will be assessed. The primary outcomes are: The rate of women requiring medications for glycemic control Mean value of the mean daily glucose charts after 2 weeks of treatment with the study products.

Official Title
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The Effect of Oral Probiotics on Glycemic Control of Women With Gestational Diabetes Mellitus - Randomized, Double Blind, Placebo Controlled Trial, Phase 4

Conditions
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Gestational Diabetes Mellitus

Intervention / Treatment
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* Dietary Supplement: Femina II
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant women who were diagnosed with GDM from 13 to 32.6 gestational weeks 18 years old and older Singleton pregnancy Exclusion Criteria: Women with pre-gestational diabetes mellitus GDM diagnosed ≥ 33 gestational weeks Women using prophylactic antimicrobial treatment Immunocompromised women Multiple pregnancy Women taking oral probiotic products who refuse to stop the consumption (food-containing probiotics is not considered an exclusion criterion).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: probiotic femina II<br>research group will receive the probiotic formula Femina II (2 capsules/day) until delivery. | Dietary Supplement: Femina II<br>* 2 capsules per day until delivery<br>|
| Placebo Comparator: Placebo<br>control group will receive a placebo (2 capsules/day) until delivery. | Other: Placebo<br>* 2 capsules per day until delivery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The rate of women who will require pharmacotherapy for glycemic control. |  | During the length of pregnancy (up to 9 months) | 
| Mean value of the mean daily glucose charts after 2 weeks of treatment with the study products. |  | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The rate of women with controlled diabetes |  | During the length of pregnancy (up to 9 months) | 
| Mean daily glucose charts |  | During the length of pregnancy (up to 9 months) | 
| Mean daily pre-prandial glucose values |  | During the length of pregnancy (up to 9 months) | 
| Mean daily post-prandial glucose values |  | During the length of pregnancy (up to 9 months) | 
| Level of glycated molecules |  | During the length of pregnancy (up to 9 months) | 
| The rate of women with mean pre-prandial values ≥ 95 mg/dl, mean post-prandial values ≥ 130 mg/dl, and mean daily glucose > 100 mg/dl |  | During the length of pregnancy (up to 9 months) | 
| The rate of cesarean deliveries |  | At delivery | 
| The rate of labor inductions |  | At delivery | 
| The rate of birth weight≥4000 gr |  | At delivery | 
| The rate of birth weight> 90th percentile |  | At delivery | 
| The rate of admission to the neonatal intensive care unit |  | Within a week from delivery | 
| Apgar score at 1 and 5 minutes from birth |  | Within 1-5 minutes after delivery | 
| The rate of neonatal hypoglycemia |  | Within 1-2 days after delivery | 
| The rate of neonatal hyperbilirubinemia |  | Within a week from delivery | 
| The rate of neonatal polycythemia |  | Within a week from delivery | 
| The rate of neonatal hypocalcemia |  | Within a week from delivery | 
| The rate of neonatal hypomagnesemia |  | Within a week from delivery | 
| Cord blood pH levels |  | At delivery | 
| The rate of neonatal malformations and developmental disorders |  | 1-2 days after delivery | 
| birth weight |  | At delivery | 
| Head circumference |  | 1-2 days after delivery | 
| Maternal adverse effects |  | During the length of pregnancy (up to 9 months) | 
| Duration of time until pharmacotherapy for glycemic control is indicated |  | During the length of pregnancy (up to 9 months) |