Probiotics (Lactobacillus Rhamnosus) in Reducing Glucose Intolerance During and After Pregnancy

Pregnancy Clinical Trial

— GRIP  

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)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01436448
• Other study ID #: 111012MED
• Status: Not yet recruiting
• Phase: Phase 3
• First received: September 7, 2011
• Last updated: September 19, 2011
• Start date: October 2011
• Est. completion date: May 2013

Study information

• Verified date: September 2011
• Source: Aga Khan University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 200
• Est. completion date: May 2013
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Glucose Intolerance
• Pregnancy

Intervention

Drug:
• Probiotics Lactobacillus Rhamnosus
Probiotics Lactobacillus Rhamnosus (1010 Colony forming Units (CFU)/day)

Locations

Country	Name	City	State
Pakistan	Aga Khan Hospital for Garden	Karachi	Sind

Sponsors (1)

Lead Sponsor	Collaborator
Aga Khan University

Country where clinical trial is conducted

Pakistan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Glucose Intolerance	Glucose Intolerance. Glucose intolerance will be assessed in accordance with ADA guidelines by OGTT. OGTT will be performed during 24-28 weeks of pregnancy	24-28 weeks of pregnancy	No
Primary	Glucose Intolerance	Glucose Intolerance. Glucose intolerance will be assessed in accordance with ADA guidelines by OGTT. OGTT will be performed during 6 to 8 weeks post partum	6 to 8 weeks post partum	No
Secondary	Feasibility	Process of recruitment rate assessed at monthly antenatal visit; recruitment rate rate assessed at monthly antenatal visit; Reasons for non-participation rate assessed at monthly antenatal visit	36 weeks	No
Secondary	Compliance	the compliance rate assessed at monthly antenatal visit; side effects rate assessed at monthly antenatal visit; drop-out rate rate assessed at monthly antenatal visit; reasons for drop-out rate assessed at monthly antenatal visit	36 weeks	No
Secondary	Maternal safety	MATERNAL OUTCOMES:( :( assessed at the time of delivery and postpartum); Maternal Mortality Maternal Weight Gain Preeclampsia Induction of labor Mode of Delivery	at the time of delivery till 42 weeks postpartum	Yes
Secondary	FETAL/NEONATAL safety	Death This will include: Still births Neonatal death Pre-term birth. Birth Trauma Macrosomia Small for Gestational Age Polyhydramnios Recurrent Hypoglycemia Large for Gestational Age Shoulder Dystocia 5-minute Apgar score: <7 Hyperbilrubinemia Respiratory Distress NICU Admission	assessed at the time of delivery till 6-8 weeks postpartum	Yes