Primary Objective: 1. To assess the impact of Winclove CLEAR on the quality of life of female rUTI patients.Secondary Objectives: 2. To assess the impact of Winclove CLEAR on the incidence of UTI and the (associated) urinary microbiota composition…
ID
Source
Brief title
Condition
- Urinary tract signs and symptoms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The differences in QoL between treatment arms according to
UTI-QoL-questionnaire data (Appendix *F1.2. UTI-QoL*) and SF-36 scores
(Appendix *F1.3. SF-36*) at day 0, 60, 120 and 180, are the primary outcome
parameters for the present study.
Secondary outcome
Secondary outcome parameters are:
2. The difference in UTI incidence between treatment arms, as measured by the
mean number of patient-reported UTI episodes during the intervention period
(Appendix *F2.2. UTI Diary*), confirmed by a microbiome analysis of urine
samples (ratio of lactobacilli to common uropathogens).
3. The difference in UTI symptom severity between treatment arms, as measured
by mean Symptom & Burden questionnaire scores (Appendix *F1.4. Symptom &
Burden*) during the intervention period.
4. The difference between treatment arms in UTI-related health-care
expenditures during the intervention period, as determined by the Health
Economics questionnaire (Appendix *F1.5. Health Economics*) at day 180.
5. The total number of subjects in the active treatment arm, and the difference
on the number of subjects between treatment arms, where probiotic strains from
the formulation are identified in urine samples at day 0, 60, 120 and 180 as
determined by a primary species-specific 16S ribosomal RNA sequencing analysis
and * if positive * a follow-up strain-specific real-time quantitative 16S
ribosomal RNA gene polymerase chain reactions.
Additionally, the difference delta (*) from baseline will be compared between
treatment arms for all previously mentioned outcome parameters
Background summary
Urinary tract infections (UTIs) have an inimical influence on patient quality
of life (QoL) and over a third of patients are likely to develop recurrent UTIs
(rUTI) within the next twelve months. Women in particular, as they are
substantially more susceptible to infection than men. Currently, few effective
prevention (or treatment) options for UTI exist, other than prophylactic
antibiotics. The adverse effects associated with repeated use of antimicrobial
prophylaxis pose an additional burden on patient QoL (e.g. Antibiotic
Associated Diarrhoea or vaginal candidiasis). Moreover, antibiotic
effectiveness is diminishing due to increasing antimicrobial resistance. Such
resistance makes UTIs increasingly difficult to treat. The current needs of
rUTI patients are therefore unmet and require new nonantibiotic prevention
options. A growing body of evidence suggest that probiotics may protect against
urogenital infections, among which UTIs. A new multispecies probiotic
formulation for the prevention of UTI (Winclove CLEAR) has therefore been
developed recently. Winclove CLEAR is developed to support the host and prevent
pathogens from migrating to the bladder. It is suggested that the probiotic
strains of Winclove CLEAR may prevent UTIs through local competition with
uropathogens and through the production of antibacterial agents. It is
therefore hypothesized that the probiotic formulation may reduce the incidence-
and symptom severity of UTIs and improve patient QoL
Study objective
Primary Objective:
1. To assess the impact of Winclove CLEAR on the quality of life of female rUTI
patients.
Secondary Objectives:
2. To assess the impact of Winclove CLEAR on the incidence of UTI and the
(associated) urinary microbiota composition in female rUTI patients.
3. To assess the impact of Winclove CLEAR on UTI symptom severity in female
rUTI patients.
4. To assess the health economic impact of Winclove CLEAR in female rUTI
patients.
5. To demonstrate the presence of probiotic strains from Winclove CLEAR in the
urine of female rUTI patients following the intervention.
Study design
A randomized, placebo-controlled, phase-2A, double-blind, single-centre,
intervention study, to assess the impact of Winclove CLEAR or matching placebo
on the QoL of female rUTI patients.
Intervention
In this two-armed clinical trial, participants will be randomized (1:1) to
either Winclove CLEAR or matching placebo. More detailed information on both
study products is provided in Appendices D6.1 and D6.2 *Technical Data Sheets*.
- Active treatment:
Participants (N = 20) consume a daily dose of 4g of Winclove CLEAR containing
4E+09 CFU of live probiotic strains L. pentosus W2 (KCA1), L. acidophilus W22,
L. plantarum W21, L. salivarius W24, L. brevis W63, L. casei W56 and L.
helveticus W74, cranberry extract (36 mg PACs) and D-mannose (1g) for a period
of 6 consecutive months.
- Placebo:
Participants (N = 20) consume a daily dose of 4g of the placebo formulation,
similar in taste/smell/appearance but without active ingredients (e.g.
probiotic, cranberry, D-mannose), for a period of 6 consecutive months.
Study burden and risks
The burden and risks of participating in the present study are low. The study
procedures form no risk for participants but may burden them slightly.
Participants are asked to collect urine samples at 4 different points in time
and when an expected episode of UTI occurs. Urine samples obtained during an
UTI episode, are stored at participants* homes in order to minimize travel and
accompanying burden for participants. The quantitative data collection does not
burden participants in any other way than time spent. Potential benefits of
consumption of Winclove CLEAR include: improvement on QoL, decreased UTI
incidence and reduced UTI symptom severity.
The consumption of both study products is considered safe and without risks.
Recent safety studies have concluded that the consumption of probiotics is
well-tolerated and generally recognized as safe across all age groups (Didari
et al., 2014; Borriello et al., 2003; Gueimonde et al., 2004; Van den Nieuwboer
et al., 2014a; Van den Nieuwboer et al., 2014b; Van den Nieuwboer et al.,
2015). Moreover, previous clinical studies with probiotic interventions in
female rUTI patients report that a probiotic intervention is not associated
with health risks or additional adverse events (Falagas et al., 2006). No
health risks are associated with the consumption of the other active
ingredients in the study product; cranberry extract and D-mannose (EFSA, 2017;
Kranj*ec et al., 2014). Furthermore, no health risks are associated with the
non-active ingredients in both Winclove CLEAR and placebo (maize starch,
hydrolyzed rice protein, sugar, and colour (E129, E133)).
As such, the investigators believe the potential benefits outweigh the
potential risks for participants, justifying the conduct of the present trial.
A list of all references can be found in the study protocol.
Hulstweg 11
Amsterdam 1032 LB
NL
Hulstweg 11
Amsterdam 1032 LB
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible for inclusion, a subject must meet all of the following criteria:
1. rUTI* for at least 2 years (defined as 3 or more episodes of UTI per year)**.
2. At least 3 UTIs in the preceding 12 months**.
3. Aged between 18 and 70 years.
4. Willing to take probiotics and refrain from UTI prophylaxis during the study.
5. Signed informed consent. ;* (Recurrent) Urinary Tract Infections
** Patient-reported
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded from participation in this study:;1. Current (complicated) suspected UTI or cystitis
2. Current antibiotic usage (or within last 4 weeks) and not willing to stop (subjects may be re-screened after 4-week wash-out)
3. Current probiotic, D-mannose or cranberry extract use (or within last 4 weeks) and not willing to stop (subjects may be re-screened after 4-week wash-out)
4. Current use of UTI prophylactics/treatment other than mentioned under point 2 & 3, which in the opinion of the investigator may significantly interfere with the evaluation of the study objectives, including: estrogen treatment, immunoprophylaxis, Methenamine Hippurate, ascorbic acid supplementation, acupuncture, UTI specific vaccines and endovesical instillation (of hyaluronic acid and chondroitin sulphate). Subjects may be re-screened after a 4-week wash-out (except for vaccines).
5. Concurrently enrolled in another intervention study (observational studies or inclusion following completion of another study is allowed (4-week wash-out))
6. Known to have a complex bladder disturbance (e.g. cystoplasty, renal and bladder calculus, significant hydronephrosis or current pyelonephritis)
7. Known to have severe renal or hepatic failure
8. Known to be severely or terminally ill
9. Known to have non-resolvable urinary obstruction
10. Known to have a history of adverse drug reaction to yoghurt or milk products or a demonstrated intolerance to the probiotics used - lactose intolerance is NOT an exclusion criterion
11. Known to be intolerant or allergic to any of the ingredients in both Winclove CLEAR and matched placebo
12. Spinal cord injury with suprapubic permanent catheter
13. Requiring full (invasive) mechanical ventilation
14. Receiving immunosuppressant medications or having an underlying immunosuppressive disease (e.g. HIV, end-stage / progressive diabetes mellitus, multiple sclerosis or cerebrovascular disease)
15. Planned oral/vaginal/urinary tract/bladder/gastrointestinal surgery during the intervention period
16. Recent oral/vaginal/urinary tract/bladder surgery/gastrointestinal (within last 3 months)
17. Pregnant females (screened with a positive pregnancy test), lactating or intending to become pregnant during the study. Women of childbearing potential need to use contraceptives
18. Use of intravaginal products (e.g. spermicides) except for menstrual products.
19. Any other condition, which, in the opinion of the investigator, may significantly interfere with the evaluation of the study objectives
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL64708.072.18 |
| OMON | NL-OMON25899 |