Clinical trial NCT01436448: Probiotics (Lactobacillus Rhamnosus) in Reducing Glucose Intolerance During and After Pregnancy
Official title: Effects of Probiotics (Lactobacillus Rhamnosus) In Reducing Glucose Intolerance During and After Pregnancy: A Double Blind Randomized Controlled Trial in Antenatal Clinic of Karachi-Pakistan (GRIP)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Glucose Intolerance
Pregnancy
Keywords: efficacy
Lactobacillus Rhamnosus
glucose intolerance
feasibility
compliance and safety
reducing glucose intolerance during and after pregnancy
Lead sponsor: Aga Khan University
Sponsor class: OTHER
First posted: 2011-09-19
Enrollment: 200
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Introduction: The overall aim of the study is to assess the efficacy of Lactobacillus Rhamnosus in reducing glucose intolerance during and after pregnancy. A second objective of the study is to determine the feasibility, compliance and safety of Lactobacillus Rhamnosus among this cohort. Within this goal is to determine whether the investigators can enroll women at high risk for developing Gestational Diabetes Mellitus (GDM) and follow them out at regular antenatal visits and 6-weeks post partum.

Women with GDM are, 7 times more at risk of developing type 2 diabetes compared with those who had a normo- glycaemic pregnancy. The population attributable risk for type 2 diabetes mellitus (DM) in women with GDM is high, and around 30 - 50% women with GDM converts into type 2 (DM) which is associated with pre-mature morbidity, mortality and high economic burden. It is evident that untreated GDM is associated with higher incidence of complications during pregnancy and increases the risk of perinatal mortality and infant morbidity. The prevalence of GDM in Pakistan is around 8%, comparatively higher than other South Asian countries. Therefore, interventions that can improve glucose regulation during pregnancy are highly important.

Probiotics, the live micro-organisms, have shown promising results in regulating glucose metabolism among pregnant mice. The effect of Probiotics on glucose metabolism is attributable to their immuno-regulatory properties. They elicit powerful anti-inflammatory capabilities by inhibiting the NF-kB pathway, which mediates microbial activation of the immune system. Further, they diminish both fermentation of polysaccharides and induction of fasting-induced adipocyte factor gene transcription. The safety of Lactobacillus Rhamnosus among pregnant women is already established in other diseases.

A placebo controlled trial from Finland on pregnant females randomized to receive either dietary counseling and Probiotics (Lactobacillus Rhamnosus), concluded improved glucose tolerance as compared to the placebo group \[OR 0.31 (95% CI 0.12, 0.78)\]. However, this study could not determine the sole effects of probiotics in reducing glucose intolerance. Nevertheless, no studies on the role of Lactobacillus Rhamnosus in regulating glucose intolerance have been conducted in any other part of the world yet. Therefore, a pilot trial to see the efficacy, compliance and feasibility of Lactobacillus Rhamnosus among pregnant females is imperative. The objectives of the investigators study are:

* To assess the efficacy of Probiotics Lactobacillus Rhamnosus (1010 Colony forming Units (CFU)/day) in reducing glucose intolerance among pregnant women attending antenatal clinic of Karachi-Pakistan.
* To assess the feasibility, compliance and safety of conducting a double blind, placebo controlled randomized trial of Lactobacillus Rhamnosus by recruiting high risk women during pregnancy attending antenatal clinics and following them up 6 weeks postpartum in Karachi-Pakistan.

Methods: For the pilot trial, women will be recruited from antenatal hospital of the city, during 12-14 weeks of gestation.

Study Design: The study will be double blind randomized, placebo controlled trial. Randomization will be done by blocked method. The dose of 1010 Colony forming Units (CFU) once daily till delivery will be given orally.

Study Endpoints and Ascertainment: Baseline information will be comprised of socioeconomic status, parity, gravida, blood pressure and obstetric history etc. The study endpoint comprises of efficacy, feasibility, compliance and safety and will be ascertained at monthly follow-up, during week 24 - 28, and 6 weeks post partum. Efficacy will be ascertained by Oral Glucose Tolerance Test (OGTT) performed at randomization and during 24-28 weeks of gestation. Feasibility and compliance will be assessed through recruitment rate, drop-out rate, reasons for drop-out, non-participation and empty drug sachet count.


Eligibility criteria: Inclusion Criteria:

High risk pregnancy ( presence of more than or equal to 1 of the following)

* Maternal age greater than or equal to 35
* Family history of diabetes among 1st degree relative defined as parents, siblings and children
* Overweight (BMI greater than 23) Women visiting the antenatal clinics during 12-14 weeks of gestation Women with Singleton pregnancy Women whose delivery is planned at the study hospital

Exclusion Criteria:

* History of GDM ( since in our setting the women are not usually screen for pre- gestational diabetes therefore it is difficult to differentiate between GDM and pre gestational diabetes)
* Known Diabetes mellitus
* Known chronic diseases ( hypothyroidism ,cardiac, renal, rheumatoid arthritis, carcinoma)
* Women maintained on medications such as: corticosteroids, Azathioprin, antiepileptic epileptic drugs.
* Known Poly Cystic Ovarian Syndrome
* Non-residents of Karachi

Primary outcomes:
measure: Glucose Intolerance
timeFrame: 24-28 weeks of pregnancy
measure: Glucose Intolerance
timeFrame: 6 to 8 weeks post partum
Secondary outcomes:
measure: Feasibility
timeFrame: 36 weeks
measure: Compliance
timeFrame: 36 weeks
measure: Maternal safety
timeFrame: at the time of delivery till 42 weeks postpartum
measure: FETAL/NEONATAL safety
timeFrame: assessed at the time of delivery till 6-8 weeks postpartum
Other outcomes:
Locations:
city: Karachi
country: Pakistan
facility: Aga Khan Hospital for Garden
state: Sind
Study officials:
affiliation: Aga Khan University
name: Bilal Ahmed, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Aga Khan University
name: Abdul Jabbar, MBBS, FRCP
role: STUDY_CHAIR
affiliation: Aga Khan University
name: Kashmira Nanji, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Aga Khan University
name: Ali Khowaja, FRCS
affiliation: Aga Khan University
name: Sarah Saleem, MBBS, MSc
affiliation: Aga Khan University
name: Rozina Sikandar, MBBS, FCPS
References:
citation: Davidson SJ, Barrett HL, Price SA, Callaway LK, Dekker Nitert M. Probiotics for preventing gestational diabetes. Cochrane Database Syst Rev. 2021 Apr 19;4(4):CD009951. doi: 10.1002/14651858.CD009951.pub3.