Clinical trial NCT03864549: The Effect of Oral Probiotics on Glycemic Control of Women With Gestational Diabetes Mellitus
Official title: The Effect of Oral Probiotics on Glycemic Control of Women With Gestational Diabetes Mellitus - Randomized, Double Blind, Placebo Controlled Trial, Phase 4
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Gestational Diabetes Mellitus
Lead sponsor: HaEmek Medical Center, Israel
Sponsor class: OTHER
First posted: 2019-03-06
Enrollment: 93
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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).

Primary outcomes:
measure: The rate of women who will require pharmacotherapy for glycemic control.
timeFrame: During the length of pregnancy (up to 9 months)
measure: Mean value of the mean daily glucose charts after 2 weeks of treatment with the study products.
timeFrame: 2 weeks
Secondary outcomes:
measure: The rate of women with controlled diabetes
timeFrame: During the length of pregnancy (up to 9 months)
measure: Mean daily glucose charts
timeFrame: During the length of pregnancy (up to 9 months)
measure: Mean daily pre-prandial glucose values
timeFrame: During the length of pregnancy (up to 9 months)
measure: Mean daily post-prandial glucose values
timeFrame: During the length of pregnancy (up to 9 months)
measure: Level of glycated molecules
timeFrame: During the length of pregnancy (up to 9 months)
measure: 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
timeFrame: During the length of pregnancy (up to 9 months)
measure: The rate of cesarean deliveries
timeFrame: At delivery
measure: The rate of labor inductions
timeFrame: At delivery
measure: The rate of birth weight≥4000 gr
timeFrame: At delivery
measure: The rate of birth weight> 90th percentile
timeFrame: At delivery
measure: The rate of admission to the neonatal intensive care unit
timeFrame: Within a week from delivery
measure: Apgar score at 1 and 5 minutes from birth
timeFrame: Within 1-5 minutes after delivery
measure: The rate of neonatal hypoglycemia
timeFrame: Within 1-2 days after delivery
measure: The rate of neonatal hyperbilirubinemia
timeFrame: Within a week from delivery
measure: The rate of neonatal polycythemia
timeFrame: Within a week from delivery
measure: The rate of neonatal hypocalcemia
timeFrame: Within a week from delivery
measure: The rate of neonatal hypomagnesemia
timeFrame: Within a week from delivery
measure: Cord blood pH levels
timeFrame: At delivery
measure: The rate of neonatal malformations and developmental disorders
timeFrame: 1-2 days after delivery
measure: birth weight
timeFrame: At delivery
measure: Head circumference
timeFrame: 1-2 days after delivery
measure: Maternal adverse effects
timeFrame: During the length of pregnancy (up to 9 months)
measure: Duration of time until pharmacotherapy for glycemic control is indicated
timeFrame: During the length of pregnancy (up to 9 months)
Other outcomes:
Locations:
city: Ashdod
country: Israel
facility: Assuta-Ashdod medical center
city: Haifa
country: Israel
facility: Rambam medical center
city: H̱olon
country: Israel
facility: Wolfson medical center
city: Tiberias
country: Israel
facility: Poriya Medical center
Study officials:
References:
citation: 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.