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

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

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:

1. The rate of women requiring medications for glycemic control
2. Mean value of the mean daily glucose charts after 2 weeks of treatment with the study products.

Study Overview

• Status: Completed
• Conditions: Gestational Diabetes Mellitus
• Intervention / Treatment: Dietary supplement: Femina II; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 93
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • Ashdod, Israel
    • Assuta-Ashdod medical center
  • Haifa, Israel
    • Rambam Medical Center
  • H̱olon, Israel
    • Wolfson Medical Center
  • Tiberias, Israel
    • Poriya Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: probiotic femina II; research group will receive the probiotic formula Femina II (2 capsules/day) until delivery.	Dietary supplement: Femina II; 2 capsules per day until delivery
Placebo Comparator: Placebo; control group will receive a placebo (2 capsules/day) until delivery.	Other: Placebo; 2 capsules per day until delivery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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)

Collaborators and Investigators

• Sponsor: HaEmek Medical Center, Israel

Publications and helpful links

General Publications

• Okesene-Gafa KA, Moore AE, Jordan V, McCowan L, Crowther CA. Probiotic treatment for women with gestational diabetes to improve maternal and infant health and well-being. Cochrane Database Syst Rev. 2020 Jun 24;6(6):CD012970. doi: 10.1002/14651858.CD012970.pub2.

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2020
• Primary Completion (Actual): June 1, 2021
• Study Completion (Actual): August 1, 2021

Study Registration Dates

• First Submitted: January 21, 2019
• First Submitted That Met QC Criteria: March 5, 2019
• First Posted (Actual): March 6, 2019

Study Record Updates

• Last Update Posted (Actual): August 3, 2021
• Last Update Submitted That Met QC Criteria: August 2, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Pregnancy Complications; Diabetes Mellitus; Diabetes, Gestational
• Other Study ID Numbers: 0003-19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No