Cranberry extracts for urinary tract infections

ISRCTN	ISRCTN32556347
DOI	https://doi.org/10.1186/ISRCTN32556347

Submission date: 02/09/2019
Registration date: 05/09/2019
Last edited: 06/11/2023

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Urological and Genital Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
Cranberries (Vaccinium macrocarpon) are a rich source of bioactive compounds, in particular proanthocyanidins (PAC), with potential impact on human health. Several studies suggest that PACs (type A) help to prevent or reduce up to 40%–50% urinary tract infections (UTIs), especially for women who have a history of recurrent infections. The hypothesized mechanism of action seems related to the capacity of PACs to reduce the adhesion of the bacteria E. coli (the most common pathogen causing UTIs) to cells lining the urinary tract and bladder.
The aim of the present project is to identify the components of cranberry (PAC and metabolites) present at urinary level and potentially responsible for UTI activity. The second part of the project will plan to identify, among the components/metabolites present at urinary level, those that may exert antimicrobial action on the microorganisms responsible for the UTIs, including Candida Albicans and E. Coli, in order to elucidate the mechanism of action.

Who can participate?
Women aged 18 - 40 years.

What does the study involve?
Participants will be randomised to take either one of two different cranberry based supplements or placebo twice a day for seven days. Urine samples will be taken for two days following the last capsule. After 30 days the participants will take a different capsule for seven days, and after another 30 days another different capsule for 30 days.

What are the possible benefits and risks of participating?
Cranberry polyphenols may be metabolised and exert a protection against urinary tract infections. There are no notable risks involved with participating.

Where is the study run from?
1. Department of Pharmaceutical Sciences, DiSFARM- Università degli Studi di Milano, Italy
2. Department of Food, Environmental and Nutritional Sciences, DeFENS-Università degli Studi di Milano, Italy
3. Department of Health Sciences, Università degli Studi di Milano, Italy

When is the study starting and how long is it expected to run for?
February to March 2019

Who is funding the study?
Indena SpA, Italy

Who is the main contact?
1. Prof. Giancarlo Aldini
giancarlo.aldini@unimi.it
2. Dr Cristian Del Bo'
cristian.delbo@unimi.it

Contact information

Prof Giancarlo Aldini
Scientific

Via Mangiagalli, 25
Milano
20133
Italy

ORCID ID	0000-0002-2355-6744
Phone	+390250319296
Email	giancarlo.aldini@unimi.it

Dr Cristian Del Bo'
Scientific

Via Celoria 2
milano
20133
Italy

ORCID ID	0000-0001-7562-377X
Phone	+390250316730
Email	cristian.delbo@unimi.it

Study information

Study design	A controlled randomized intervention study
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Other
Study type	Prevention
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet.
Scientific title	Profiling Vaccinium macrocarpon components and metabolites in human urine and the urine ex-vivo effect on Candida albicans adhesion and biofilm-formation
Study acronym	CRAME
Study objectives	The present pilot study aims to test the hypothesis that some bioactive compounds from standardized cranberry extracts are absorbed, metabolized and excreted in urine and can exert protection against urinary tract infections
Ethics approval(s)	Approved 18/12/2018, Ethics Committee of the University of Milan (Università degli Studi di Milano, Via Festa del Perdono 7, 20122, Milano, Italy; +39 2 503 12667; comitato.etico@unimi.it), ref: 57/18
Health condition(s) or problem(s) studied	Urinary tract infection
Intervention	Ten healthy women will be enrolled and randomized for the intervention. Subjects will be randomized, based on a computer randomization plan. Two different food supplements, based on standardized cranberry extracts, and a placebo will be tested: 1. Cranberry capsules (Anthocran, Vaccinium macrocarpon Aiton.) 2. Cranberry capsules (Antocran Phytosome, Vaccinium macrocarpon Aiton. containing sunflower lecithin) 3. Placebo capsules (containing microcrystalline cellulose, silicon dioxide, magnesium stearate) Each subject will consume two capsules per day (one in the morning and on in the evening) of cranberry extracts or placebo. Each treatment will be 7-day long and separated by at least 30-day wash-out period. At the beginning (before capsule intake) and at the end of the intervention (7 days), urine will be collected at time 1, 2, 4, 6, 10,12, 14, 24, 48 hours from the intake of the last capsule.
Intervention type	Supplement
Primary outcome measure	Detection at time 1, 2, 4, 6, 10,12, 14, 24, 48 hours (from the intake of the last capsule) of cranberry bioactive constituents in urine (type A proanthocyanidin) and metabolites including hydroxybenzoic acids and valerolactones evaluated by high-resolution mass spectrometry.
Secondary outcome measures	1. Detection of other potential cranberry polyphenol metabolites in urines evaluated by high-resolution mass spectrometry 2. Ex-vivo inhibition of Candida albicans adhesion and biofilm formation by using the urine collected from the subjects at different time points
Overall study start date	10/04/2018
Completion date	31/05/2019

Eligibility

Participant type(s)	Healthy volunteer
Age group	Adult
Lower age limit	18 Years
Upper age limit	40 Years
Sex	Female
Target number of participants	10
Total final enrolment	13
Key inclusion criteria	1. Women 2. Age 18-40 years 3. BMI 18-25 kg/m2 4. Healthy
Key exclusion criteria	1. Smokers 2. Allergy to cranberry 3. Gastrointestinal disorder 4. Liver and renal disease 5. Antibiotic treatment
Date of first enrolment	15/01/2019
Date of final enrolment	15/02/2019

Locations

Countries of recruitment

Italy

Study participating centres

Department of Pharmaceutical Sciences, DiSFARM- Università degli Studi di Milano

Via L. Mangiagalli, 25
MILANO
20133
Italy

Department of Food, Environmental and Nutritional Sciences, DeFENS-Università degli Studi di Milano

Via L. Mangiagalli, 25
MILANO
20133
Italy

Department of Health Sciences, Università degli Studi di Milano

Via Di Rudinì 8
MILANO
20146
Italy

Sponsor information

Indena Spa
Industry

Viale Ortles 12
Milano
20139
Italy

Phone	+3902574961
Email	antonella.riva@indena.com
Website	http://www.indena.com/company-profile/
"ROR"	https://ror.org/052d5f872

Funders

Funder type

Industry

Indena SpA

No information available

Results and Publications

Intention to publish date	31/12/2019
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Data sharing statement to be made available at a later date
Publication and dissemination plan	Planned publication in a high-impact peer-reviewed journal
IPD sharing plan	The current data sharing plans for this study are unknown and will be available at a later date

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/03/2020	20/05/2020	Yes	No
Results article	Biofilm Inhibition	13/07/2021	06/11/2023	Yes	No

Editorial Notes

06/11/2023: Publication reference added.
20/05/2020: The following changes have been made:
1. Publication reference added.
2. The total final enrolment number has been added.
06/09/2019: Internal review.
04/09/2019: Trial’s existence confirmed by Universita Degli Studi di Milano