A Probiotic Based Intervention in Pregnancies Complicated by GDM

Official title

A Single-center, Randomized, Double-blind, Parallel-group, Placebo-controlled Trial of a Probiotic-based Intervention to Improve Glycemic Control in Pregnancies Complicated by Gestational Diabetes.

Overview

This study is a single center randomized control trial of a probiotic based intervention in pregnancies complicated by gestational diabetes. A healthy gut microbiome is now recognized as a key component of human health and dysbiosis of the gut microbiome, including lack of diversity, is believed to contribute to the development of many diseases and alter glucose control. The study aims to explore whether this probiotic intervention will improve glucose control and change the gut microbiome. Participants may be enrolled and randomized after diagnosis of gestational diabetes between 24 and 31 weeks gestation. 115 participants will be randomized in a ratio of 2 in the probiotic intervention group to 1 in the placebo group. Participants will stop taking the intervention at 6 weeks postpartum. At this time, they will be unblinded and offered the option of participating in an open-label extension of the intervention until 6 months postpartum.

Detailed description

The chosen study design is a single-center, randomized, double-blind, parallel-group, placebo-controlled trial. Participants will be randomized by 2:1 to probiotic intervention or placebo. This is an exploratory study examining the impact of the intervention on glucose control among pregnant persons diagnosed with gestational diabetes.

Participants may be enrolled and randomized after diagnosis of GDM between 240 and 316 weeks gestation. Participants will stop taking the intervention at 6 weeks postpartum. At this time, they will be unblinded and offered the option of participating in an open-label extension of the intervention until 6 months postpartum.

Participants will be seen for up to 4 study visits: 3 mandatory visits in the main study and 1 in the optional extension. Brief visit outlines are below.

Visit 1 at 24-31 weeks gestation:

* eligibility confirmation * consent * randomization * weight, height, blood pressure, method of glucose control from chart * dispense investigational product * baseline survey * pregnancy history questionnaire * Diet Screening for Adults in Canada (D-SAC) * Automated Self-Administered 24-Hour Dietary Recall (ASA) x2 * Libre2 1 week of monitoring data * concommitant medication log * maternal rectal swab

Visit 2 at 37 weeks gestation:

* weight, height, blood pressure, method of glucose control from chart * dispense and reconcile investigational product * D-SAC * ASA x2 * Libre2 1 week of monitoring data * concommitant medication log * maternal rectal swab * adverse event log

Delivery:

* infant consent * weight, height, blood pressure, method of glucose control from chart * delivery chart review * Libre2 1 week of monitoring data * weigh placenta * concommitant medication log * adverse event log

Visit 3 at 6 weeks postpartum:

* reconcile investigational product * unblind * postpartum survey * D-SAC * ASA x2 * concommitant medication log * maternal rectal swab * infant fecal swab * adverse event log * study completion form

Optional Open Label Extension - At 6 weeks postpartum, once all study components are complete, participants will be unblinded and invited to participate in an open label, single arm extension of the intervention till 6 months postpartum. Participants who agree to participate in the extension of the intervention will be provided with additional open-label product until 6 months postpartum.

Visit E1 (open label extension, visit done with V3)

* enroll in extension if desired * dispense open label product * maternal and infant consent

Visit E2 at 6 months postpartum:

* Chart review * D-SAC * ASA x2 * concommitant medication log * maternal rectal swab * infant fecal swab * adverse event log * study completion form

Interventions

• Dietary supplement 5-strain probiotic plus prebiotic natural health product
  The investigational product is a 5-strain probiotic plus prebiotic natural health product for patients with Type 2 diabetes. Other ingredients include oligofructose, grape food color, magnesium stearate, silica and a delayed release capsule. Recommended storage is in a refrigerated environment at approximately 4°C. The product should not be frozen. It is recommended that the product be used within 2 months after opening the bottle. Participants are asked to take 2 capsules daily with food, 1 in
• Other Placebo
  Ingredients include oligofructose, grape food color, magnesium stearate, silica and a delayed release capsule. Recommended storage is in a refrigerated environment at approximately 4°C. The product should not be frozen. It is recommended that the product be used within 2 months after opening the bottle. Participants are asked to take 2 capsules daily with food, 1 in the morning and 1 in the evening.

Primary outcome measures

• Glycemic Control - Mean Fasting Glucose [Time frame: 38th week of pregnancy (37+0-37+6 weeks gestation)]
• Glycemic Control - Mean Glucose [Time frame: 38th week of pregnancy (37+0-37+6 weeks gestation)]
• Glycemic Control - Time in Ranges [Time frame: 38th week of pregnancy (37+0-37+6 weeks gestation)]
• Glycemic Control - HbA1C [Time frame: 38th week of pregnancy (37+0-37+6 weeks gestation)]

Secondary outcome measures (12)

• Glycemic Therapy Requirements [Time frame: At Delivery]
• Group B Strep [Time frame: At Delivery]
• Pregnancy Outcomes - Gestational Age at Delivery [Time frame: At Delivery]
• Pregnancy Outcomes - Mode of Delivery [Time frame: At Delivery]
• Maternal Outcomes - Severe Maternal Morbidity [Time frame: Within 42 days of delivery]
• Maternal Outcomes - Weight Change [Time frame: At Delivery]
• Neonatal Outcomes - Birthweight [Time frame: At delivery]
• Neonatal Outcomes - NICU Admissions [Time frame: Within 28 days of delivery]
• Neonatal Outcomes - Hypoglycemia [Time frame: Within 72 hours of delivery.]
• Maternal Gut Microbiome - Metagenome [Time frame: 38th week of pregnancy, 6 weeks postpartum, 6 months postpartum]
• Maternal Gut Microbiome - Metabolome [Time frame: 38th week of pregnancy, 6 weeks postpartum, 6 months postpartum]
• Infant Gut Microbiome - Metagenome [Time frame: 6 Weeks of Age]

Eligibility criteria

Inclusion criteria

Participants must meet all the following inclusion criteria to be eligible for enrollment into the study:

• Participants who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
• Participant has given written consent after study has been explained according to local regulatory requirements and before any study specific procedures.
• Age ≥16 years at the time of consent.
• Singleton pregnancy.
• Live fetus (documented positive fetal heartbeat prior to recruitment)
• Diagnosis of Gestational Diabetes (GDM) at the time of inclusion (documented 50g glucose challenge test (>11.1 mmol/L) and/or 75g oral glucose tolerance test with results exceeding the normal range (fasting >5.3 mmol/L, 1 hour >10.6 mmol/L, or 2 hour > 8.9 mmol/L)
• Willing to provide fecal swab samples.
• Willing to wear a continuous glucose monitor from enrollment until delivery and for 14 days at 6 weeks postpartum.
• Willing to provide results from the continuous glucose monitor using the associated app on their mobile device.
• Willing to complete surveys related to diet, pregnancy history, and health history.
• Plan to reside in the study area at least until delivery and to deliver at Kingston Health Sciences Center (KHSC).
• Willing to test for Group B Strep during pregnancy

Exclusion criteria

Any individual meeting any of the following criteria is not eligible for participation in this study:

• Current diagnosis of severe gestational hypertension, preeclampsia, HELLP, intrauterine growth restriction, or other clinically significant pregnancy complication(s) at the time of enrollment.
• Sustained use of substances, such as alcohol, cannabis, nicotine, and other recreational drugs. This is defined as any use after the patient is aware that they are pregnant OR as per the discretion of the investigator.
• Systemic antibiotic or antifungal use ≤3 months prior to enrollment.
• Active clinical infection(s), such as sexually transmitted infections, urinary tract infectionss, systemic infections, periodontal disease or positive blood cultures ≤3 months prior to enrollment
• Acute or chronic clinically significant abnormality or poorly controlled pre-existent co-morbidities, such as autoimmune disease, inflammatory bowel disease (IBD), Crohn's, colitis, or other conditions, that, in the opinion of the investigator, might confound study results.
• Prescription medications, especially relating to gastric function, or immunosuppressants, that, in the opinion of the investigator, might confound study results.
• Known hypersensitivity to >4 first-line antimicrobial therapies against Akkermansia muciniphila, Clostridium beijerinckii, Clostridium butyricum, Anaerobutyricum hallii: Penicillin, Piperacillin, Tetracycline, Amoxicillin, Ampicillin.
• Known hypersensitivity to >4 first-line antimicrobial therapies against Bifidobacterium infantis Bi-26TM: Gentamicin, Kanamycin, Streptomycin, Tetracycline, Erythromycin, Clindamycin, Ampicillin, Vancomycin.
• Any conditions that, in the Investigator's judgement, may interfere with participant's ability to comply with study procedures or receipt of prenatal care, such as behavioural or cognitive impairment or neuropsychiatric illness.
• Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational vaccine/product.
• Pill swallowing phobia or inability to swallow pills.
• Not taking any other probiotic supplements during the study intervention period.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Canada · 1 center

• Queen's University & Kingston Health Sciences Centre — Kingston

Identifiers

NCT: NCT06794723 · 6043857

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗