Intravaginal LACTIN-V for Prevention of Recurrent Urinary Tract Infection

NCT00305227 | Completed Phase 2 Results DMC

• 3 other identifiers: 285525P01DK053369UW/LB-001
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Recurrent urinary tract infections (RUTIS) continue to be a major health problem in women and are now complicated by increasing antibiotic resistance. New preventive approaches are needed. Because most women with RUTI lack the normal protective Lactobacillus (LB) in their vaginal flora, we hypothesized that restoration of LB would reduce RUTIS. In this trail, women with recent UTI are randomized to receive either LB or placebo vaginal capsules and are followed for side effects, for colonization with LB and for occurrence of RUTI over hte next four months.

Conditions

Urinary Tract Infection

Keywords

urinary tract infection; cystitis; Lactobacillus; probiotic; prevention

Outcome Measures

Primary Outcomes (1)

• Incidence of Urinary Tract Infection

  Recurrent urinary tract infection after initiation of intervention. Culture-confirmed to contain uropathogen.

  10 weeks

Secondary Outcomes (1)

• Incidence of Vaginal Discharge

  4 months

Study Arms (2)

Lactin-V

EXPERIMENTAL

Vaginal capsule containing Lactobacillus crispatus in high concentration. Self-administered once daily for 5 days during the 1st week. Self-administered once weekly for 10 weeks.

Drug: Lactin-V

Placebo

PLACEBO COMPARATOR

Vaginal capsule - placebo. Self-administered once daily for 5 days during the 1st week. Self-administered once weekly for 10 weeks.

Drug: Placebo

Interventions

Lactin-V DRUG

Also known as: no other names

Lactin-V

Placebo DRUG

Also known as: no other names

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• pre-menopausal woman aged 18-40 years
• current symptomatic uncomplicated cystitis
• cystitis is treated with trimethoprim-sulfamethoxazole (TMP-SMX)
• completion of screening procedures
• negative screening monolayer Pap smear or hysterectomy
• history of at least two prior symptomatic UTI's treated within the past 12 months or one pior symptomatic UTI treated in the past six months
• agree to return for the Randomization Visit (Visit 2)
• regular menstrual cycles or amenorrheic due to use of a long acting progestin, continuous use of oral contraceptives or hysterectomy
• willing to insert vaginal capsules without an applicator
• capable of providing informed consent
• able to read and understand English
• agree to abstain from self-medication with antibiotics for UTI symptoms
• agree to abstain from antibiotic prophylaxis for recurrent UTI
• agree to abstain from the use of any other intra-vaginal product
• agree to abstain from sexual intercourse for 24 hours after capsule insertion

You may not qualify if:

• complicated cystitis or uncomplicated pyelonephritis.
• cystitis at Visit 1 not treated with TMP-SMX
• uropathogen resistant to TMP-SMX isolated at Visit 1 and persistent symptoms at Visit 2 or failure to achieve a significant reduction in urine wbc count at Visit 2
• vaginal or cervical infection, currently or within the past 21 days, with bacterial vaginosis (treated, symptomatic infection), Trichomonas vaginalis, Neisseria gonorrhoeae, Chlamydia trachomatis or Herpes Simplex
• symptomatic bacterial vaginosis at Visit 1
• high risk for sexually transmitted diseases and/or HIV, including:
• diagnosis of N. gonorrhoeae, C. trachomatis or T. vaginalis on two or more occasions during the previous six months;
• sexual intercourse with a homosexual/bisexual male in the last 10 years;
• sexual intercourse with an injection drug user or sex worker in the last 10 years; or
• shared needles for injected drugs in the last 10 years.
• chronic vaginal, urinary or pelvic symptoms not attributable to UTI
• recurrent bacterial vaginosis (three or more symptomatic, treated infections in the prior 12 months)
• pregnancy or within two months of last pregnancy
• lactation
• antibiotic therapy fewer than three days prior to Randomization Visit

Sponsors & Collaborators

• University of Washington: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• Osel, Inc.: collaborator

Study Sites (1)

Hall Health Primary Care Center, University of Washington

Seattle, Washington, 98195, United States

Location

Related Publications (14)

• Giorgi A, Torriani S, Dellaglio F, Bo G, Stola E, Bernuzzi L. Identification of vaginal lactobacilli from asymptomatic women. Microbiologica. 1987 Oct;10(4):377-84.

  PMID: 3695985 BACKGROUND

• Antonio MA, Hawes SE, Hillier SL. The identification of vaginal Lactobacillus species and the demographic and microbiologic characteristics of women colonized by these species. J Infect Dis. 1999 Dec;180(6):1950-6. doi: 10.1086/315109.

  PMID: 10558952 BACKGROUND

• Antonio MA, Hillier SL. DNA fingerprinting of Lactobacillus crispatus strain CTV-05 by repetitive element sequence-based PCR analysis in a pilot study of vaginal colonization. J Clin Microbiol. 2003 May;41(5):1881-7. doi: 10.1128/JCM.41.5.1881-1887.2003.

  PMID: 12734221 BACKGROUND

• Foxman B, Barlow R, D'Arcy H, Gillespie B, Sobel JD. Urinary tract infection: self-reported incidence and associated costs. Ann Epidemiol. 2000 Nov;10(8):509-15. doi: 10.1016/s1047-2797(00)00072-7.

  PMID: 11118930 BACKGROUND

• Stamm WE, Counts GW, Wagner KF, Martin D, Gregory D, McKevitt M, Turck M, Holmes KK. Antimicrobial prophylaxis of recurrent urinary tract infections: a double-blind, placebo-controlled trial. Ann Intern Med. 1980 Jun;92(6):770-5. doi: 10.7326/0003-4819-92-6-770.

  PMID: 6992677 BACKGROUND

• Gupta K, Scholes D, Stamm WE. Increasing prevalence of antimicrobial resistance among uropathogens causing acute uncomplicated cystitis in women. JAMA. 1999 Feb 24;281(8):736-8. doi: 10.1001/jama.281.8.736.

  PMID: 10052444 BACKGROUND

• Hooton TM, Scholes D, Gupta K, Stapleton AE, Roberts PL, Stamm WE. Amoxicillin-clavulanate vs ciprofloxacin for the treatment of uncomplicated cystitis in women: a randomized trial. JAMA. 2005 Feb 23;293(8):949-55. doi: 10.1001/jama.293.8.949.

  PMID: 15728165 BACKGROUND

• Reid G, Bruce AW, Fraser N, Heinemann C, Owen J, Henning B. Oral probiotics can resolve urogenital infections. FEMS Immunol Med Microbiol. 2001 Feb;30(1):49-52. doi: 10.1111/j.1574-695X.2001.tb01549.x.

  PMID: 11172991 BACKGROUND

• Stamey TA, Sexton CC. The role of vaginal colonization with enterobacteriaceae in recurrent urinary infections. J Urol. 1975 Feb;113(2):214-7. doi: 10.1016/s0022-5347(17)59447-1.

  PMID: 803573 BACKGROUND

• Gupta K, Stapleton AE, Hooton TM, Roberts PL, Fennell CL, Stamm WE. Inverse association of H2O2-producing lactobacilli and vaginal Escherichia coli colonization in women with recurrent urinary tract infections. J Infect Dis. 1998 Aug;178(2):446-50. doi: 10.1086/515635.

  PMID: 9697725 BACKGROUND

• Hooton TM, Fihn SD, Johnson C, Roberts PL, Stamm WE. Association between bacterial vaginosis and acute cystitis in women using diaphragms. Arch Intern Med. 1989 Sep;149(9):1932-6.

  PMID: 2673116 BACKGROUND

• Hooton TM, Roberts PL, Stamm WE. Effects of recent sexual activity and use of a diaphragm on the vaginal microflora. Clin Infect Dis. 1994 Aug;19(2):274-8. doi: 10.1093/clinids/19.2.274.

  PMID: 7986899 BACKGROUND

• Osset J, Bartolome RM, Garcia E, Andreu A. Assessment of the capacity of Lactobacillus to inhibit the growth of uropathogens and block their adhesion to vaginal epithelial cells. J Infect Dis. 2001 Feb 1;183(3):485-91. doi: 10.1086/318070. Epub 2000 Dec 29.

  PMID: 11133381 BACKGROUND

• Stapleton AE, Au-Yeung M, Hooton TM, Fredricks DN, Roberts PL, Czaja CA, Yarova-Yarovaya Y, Fiedler T, Cox M, Stamm WE. Randomized, placebo-controlled phase 2 trial of a Lactobacillus crispatus probiotic given intravaginally for prevention of recurrent urinary tract infection. Clin Infect Dis. 2011 May;52(10):1212-7. doi: 10.1093/cid/cir183. Epub 2011 Apr 14.

  PMID: 21498386 DERIVED

MeSH Terms

Conditions

Urinary Tract Infections; Cystitis

Condition Hierarchy (Ancestors)

Infections; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Bladder Diseases

Results Point of Contact

• Title: Ann Stapleton, MD
• Organization: University of Washington

stapl@uw.edu

206-616-4121

Study Officials

• Ann E Stapleton, MD

  University of Washington

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 20, 2006
• First Posted: March 21, 2006
• Study Start: March 1, 2006
• Primary Completion: April 1, 2012
• Study Completion: April 1, 2012
• Last Updated: April 14, 2023
• Results First Posted: July 4, 2014

Record last verified: 2023-03

Locations

US (1)