Preventing Preterm Birth With Probiotics

NCT02692820 | Completed DMC

• 1 other identifier: 010294QM
• Study Type: interventional
• Target: 304
• Locations: 1 country
• Sites: 2

Brief Summary

Babies born preterm (before completing 37 weeks in the womb) are at increased risk of long-term disability and death. The investigators do not fully understand the cause(s) of preterm birth but it occurs more frequently when the normal, healthy bacteria (called Lactobacilli) in a woman's birth canal are replaced with unhealthy bacteria. Previous attempts to get rid of the unhealthy bacteria with antibiotics have not shown to affect the risk of preterm birth. The reason for this may be that what is required is the replacement of Lactobacilli in the birth canal. This can be done by asking women to take capsules containing lactobacilli once daily. To study whether oral Lactobacilli capsules compared with dummy capsules can reduce the risk of preterm birth, a large study involving approximately 10,000 women would be required. But the investigators do not know whether women would agree to take part in and complete such a study, and this is what the investigators wish to study in the small, initial study described here. The results of this study will show whether probiotics produce the desired biological effects on vaginal bacteria, and whether it would be feasible to perform the larger, definitive study of their effectiveness in prevention of preterm birth.

Conditions

Preterm Birth

Keywords

Preterm; Probiotic

Outcome Measures

Primary Outcomes (3)

• The microbiological effect of the probiotic on the vaginal flora during pregnancy,

  To evaluate the microbiological effects of probiotics on vaginal flora the investigators will compare treatments groups regarding the proportion of women with bacterial vaginosis (BV) at delivery and the proportion of women with vaginal colonisation with intervention strains at delivery.

  18 months

• The proportion of eligible women recruited into the trial

  The primary analysis will also involve the estimation of the proportions of the primary outcomes (i.e. eligible women recruited into the trial, recruited women who complete the trial and adhere to the intervention treatment until delivery).

  18 months

• The proportions of recruited women who complete the trial and adhere to the intervention until delivery

  The primary analysis will also involve the estimation of the proportions of the primary outcomes (i.e. eligible women recruited into the trial, recruited women who complete the trial and adhere to the intervention treatment until delivery).

  18 months

Secondary Outcomes (2)

• Questionnaire/interview assessment of reasons for participation and non-participation, trial attrition, and non-adherence to trial protocol by ethnic groups (subject to funding)

  18 months

• Core outcomes for use in studies on preterm birth prevention from case report forms

  18 months

Study Arms (2)

Probiotic

EXPERIMENTAL

Those who provide consent will be randomised to receive once daily for the remainder of their pregnancy capsules of probiotics (containing Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 (each at 2.5 x 109 colony forming units (CFUs)). The product contains freeze-dried bacteria and excipients in a gelatin capsule.

Dietary Supplement: Probiotic

Placebo

PLACEBO COMPARATOR

Those who provide consent will be randomised to receive once daily for the remainder of their pregnancy capsules of the placebo containing excipients alone in a gelatin capsule

Other: Placebo Comparator

Interventions

Probiotic DIETARY_SUPPLEMENT

The probiotic capsule contains the two probiotics Lactobacillus rhamnosus GR-1 (GR-1) and Lactobacillus reuteri RC-14 (RC-14). The product contains freeze-dried bacteria and excipients in a gelatin capsule;

Probiotic

Placebo Comparator OTHER

The placebo contains excipients alone in a gelatin capsule

Placebo

Eligibility Criteria

• Age: 16 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Women aged 16 years and over at the time of the booking appointment.
• Women who are between 9-14 weeks gestation at the time of the dating scan.

You may not qualify if:

• Lack of informed, written consent

Sponsors & Collaborators

• Queen Mary University of London: lead

Study Sites (2)

Barts Health NHS Trust

London, E1 1BB, United Kingdom

Location

Homerton University Hospital

London, E9 6SR, United Kingdom

Location

Related Publications (28)

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  BACKGROUND

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  PMID: 15001150 BACKGROUND

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  PMID: 20349187 BACKGROUND

• Boyle JD, Boyle EM. Born just a few weeks early: does it matter? Arch Dis Child Fetal Neonatal Ed. 2013 Jan;98(1):F85-8. doi: 10.1136/archdischild-2011-300535. Epub 2011 Aug 24.

  PMID: 21865487 BACKGROUND

• Saigal S, Doyle LW. An overview of mortality and sequelae of preterm birth from infancy to adulthood. Lancet. 2008 Jan 19;371(9608):261-9. doi: 10.1016/S0140-6736(08)60136-1.

  PMID: 18207020 BACKGROUND

• Mangham LJ, Petrou S, Doyle LW, Draper ES, Marlow N. The cost of preterm birth throughout childhood in England and Wales. Pediatrics. 2009 Feb;123(2):e312-27. doi: 10.1542/peds.2008-1827.

  PMID: 19171583 BACKGROUND

• Goldenberg RL, Hauth JC, Andrews WW. Intrauterine infection and preterm delivery. N Engl J Med. 2000 May 18;342(20):1500-7. doi: 10.1056/NEJM200005183422007. No abstract available.

  PMID: 10816189 BACKGROUND

• Blencowe H, Cousens S, Oestergaard MZ, Chou D, Moller AB, Narwal R, Adler A, Vera Garcia C, Rohde S, Say L, Lawn JE. National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications. Lancet. 2012 Jun 9;379(9832):2162-72. doi: 10.1016/S0140-6736(12)60820-4.

  PMID: 22682464 BACKGROUND

• Office for National Statistics, (2014b). Childhood, Infant and Perinatal Mortality in England and Wales, 2012. [Internet] Available at: http://www.ons.gov.uk/ons/rel/vsob1/child-mortality-statistics--childhood--infant-and-perinatal/2012/rft-cms-2012.xls

  BACKGROUND

• Costeloe KL, Hennessy EM, Haider S, Stacey F, Marlow N, Draper ES. Short term outcomes after extreme preterm birth in England: comparison of two birth cohorts in 1995 and 2006 (the EPICure studies). BMJ. 2012 Dec 4;345:e7976. doi: 10.1136/bmj.e7976.

  PMID: 23212881 BACKGROUND

• Guaschino S, De Seta F, Piccoli M, Maso G, Alberico S. Aetiology of preterm labour: bacterial vaginosis. BJOG. 2006 Dec;113 Suppl 3:46-51. doi: 10.1111/j.1471-0528.2006.01122.x.

  PMID: 17206964 BACKGROUND

• Donders GG, Van Calsteren K, Bellen G, Reybrouck R, Van den Bosch T, Riphagen I, Van Lierde S. Predictive value for preterm birth of abnormal vaginal flora, bacterial vaginosis and aerobic vaginitis during the first trimester of pregnancy. BJOG. 2009 Sep;116(10):1315-24. doi: 10.1111/j.1471-0528.2009.02237.x. Epub 2009 Jun 17.

  PMID: 19538417 BACKGROUND

• Hawes SE, Hillier SL, Benedetti J, Stevens CE, Koutsky LA, Wolner-Hanssen P, Holmes KK. Hydrogen peroxide-producing lactobacilli and acquisition of vaginal infections. J Infect Dis. 1996 Nov;174(5):1058-63. doi: 10.1093/infdis/174.5.1058.

  PMID: 8896509 BACKGROUND

• Wilks M, Wiggins R, Whiley A, Hennessy E, Warwick S, Porter H, Corfield A, Millar M. Identification and H(2)O(2) production of vaginal lactobacilli from pregnant women at high risk of preterm birth and relation with outcome. J Clin Microbiol. 2004 Feb;42(2):713-7. doi: 10.1128/JCM.42.2.713-717.2004.

  PMID: 14766841 BACKGROUND

• Mosbah A, Mesbah MR. (2009) A study of the role of hydrogen peroxide production by lactobacilli in preterm labor. Int J Med Med Sci, 1:388-95.

  BACKGROUND

• Brocklehurst P, Gordon A, Heatley E, Milan SJ. Antibiotics for treating bacterial vaginosis in pregnancy. Cochrane Database Syst Rev. 2013 Jan 31;2013(1):CD000262. doi: 10.1002/14651858.CD000262.pub4.

  PMID: 23440777 BACKGROUND

• Cooper NA, Moores R; East London Preterm Prevention Collaboration. A review of the literature regarding nutritional supplements and their effect on vaginal flora and preterm birth. Curr Opin Obstet Gynecol. 2014 Dec;26(6):487-92. doi: 10.1097/GCO.0000000000000126.

  PMID: 25379767 BACKGROUND

• Othman M, Neilson JP, Alfirevic Z. Probiotics for preventing preterm labour. Cochrane Database Syst Rev. 2007 Jan 24;2007(1):CD005941. doi: 10.1002/14651858.CD005941.pub2.

  PMID: 17253567 BACKGROUND

• Unlu C, Donders G. Use of lactobacilli and estriol combination in the treatment of disturbed vaginal ecosystem: a review. J Turk Ger Gynecol Assoc. 2011 Dec 1;12(4):239-46. doi: 10.5152/jtgga.2011.57. eCollection 2011.

  PMID: 24592002 BACKGROUND

• Zhao T-F, Zhong L, Luo D.(2010) Living preparation of lactobacillus versus metronidazole for bacterial vaginosis in pregnancy: a systematic review. Chin J Evid-based Med, 10:1338-44.

  BACKGROUND

• Myhre R, Brantsaeter AL, Myking S, Gjessing HK, Sengpiel V, Meltzer HM, Haugen M, Jacobsson B. Intake of probiotic food and risk of spontaneous preterm delivery. Am J Clin Nutr. 2011 Jan;93(1):151-7. doi: 10.3945/ajcn.110.004085. Epub 2010 Oct 27.

  PMID: 20980489 BACKGROUND

• Yeganegi M, Watson CS, Martins A, Kim SO, Reid G, Challis JR, Bocking AD. Effect of Lactobacillus rhamnosus GR-1 supernatant and fetal sex on lipopolysaccharide-induced cytokine and prostaglandin-regulating enzymes in human placental trophoblast cells: implications for treatment of bacterial vaginosis and prevention of preterm labor. Am J Obstet Gynecol. 2009 May;200(5):532.e1-8. doi: 10.1016/j.ajog.2008.12.032. Epub 2009 Mar 14.

  PMID: 19285652 BACKGROUND

• Dugoua JJ, Machado M, Zhu X, Chen X, Koren G, Einarson TR. Probiotic safety in pregnancy: a systematic review and meta-analysis of randomized controlled trials of Lactobacillus, Bifidobacterium, and Saccharomyces spp. J Obstet Gynaecol Can. 2009 Jun;31(6):542-552. doi: 10.1016/S1701-2163(16)34218-9.

  PMID: 19646321 BACKGROUND

• Lindsay KL, Brennan L, McAuliffe FM. Acceptability of and compliance with a probiotic capsule intervention in pregnancy. Int J Gynaecol Obstet. 2014 Jun;125(3):279-80. doi: 10.1016/j.ijgo.2014.01.004. Epub 2014 Feb 19. No abstract available.

  PMID: 24636629 BACKGROUND

• Krauss-Silva L, Moreira ME, Alves MB, Braga A, Camacho KG, Batista MR, Almada-Horta A, Rebello MR, Guerra F. A randomised controlled trial of probiotics for the prevention of spontaneous preterm delivery associated with bacterial vaginosis: preliminary results. Trials. 2011 Nov 8;12:239. doi: 10.1186/1745-6215-12-239.

  PMID: 22059409 BACKGROUND

• Reid G, Charbonneau D, Erb J, Kochanowski B, Beuerman D, Poehner R, Bruce AW. Oral use of Lactobacillus rhamnosus GR-1 and L. fermentum RC-14 significantly alters vaginal flora: randomized, placebo-controlled trial in 64 healthy women. FEMS Immunol Med Microbiol. 2003 Mar 20;35(2):131-4. doi: 10.1016/S0928-8244(02)00465-0.

  PMID: 12628548 BACKGROUND

• 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.

  PMID: 33870484 DERIVED

• Husain S, Allotey J, Drymoussi Z, Wilks M, Fernandez-Felix BM, Whiley A, Dodds J, Thangaratinam S, McCourt C, Prosdocimi EM, Wade WG, de Tejada BM, Zamora J, Khan K, Millar M. Effects of oral probiotic supplements on vaginal microbiota during pregnancy: a randomised, double-blind, placebo-controlled trial with microbiome analysis. BJOG. 2020 Jan;127(2):275-284. doi: 10.1111/1471-0528.15675. Epub 2019 Apr 1.

  PMID: 30932317 DERIVED

MeSH Terms

Conditions

Premature Birth

Interventions

Probiotics

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Khalid S Khan, Phd

  Queen Mary University of London

  PRINCIPAL INVESTIGATOR

• Rehan Khan, MD

  Barts Health NHS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2015
• First Posted: February 26, 2016
• Study Start: May 1, 2016
• Primary Completion: June 1, 2017
• Study Completion: June 1, 2017
• Last Updated: September 20, 2017

Record last verified: 2017-01

Locations

GB (2)