CLINICAL STUDIES SUMMARY

(For Health Professionals Only)

Cysticlean® (CYS), is a special American cranberry extract with a very high proanthocyanidins (PAC) concentration (240 mg per capsule or sachet) which has been available in Europe since 2007. Several preclinical studies have proven that CYS has a high anti-adhesion activity (AAA) of up to 90% against Escherichia coli (Ec). This AAA is PAC concentration related: the more PAC the more AAA. It is available in boxes of 10, 30 and 60 capsules and 30 sachets.

AAA activity has been proven to be related to its efficacy in treating and preventing urinary tract infections (UTI). Several clinical studies have been conducted and published with CYS treating and preventing UTI in children with urological congenital diseases, fertile and post-menopausal women, post-coital infections and women and elderly men including up to 608 patients (242 children, 160 elderly, 206 adults) giving a very good profile of safety and efficacy. No serious adverse reaction/side effects have been reported from clinical studies or from the market due to the administration of CYS. The CYS profile strongly suggests it could be an alternative to antibiotic treatment at a time when such treatment is failing due to the continuous increase in bacteria antibiotic resistance

SUMMARY OF THE PRE-CLINICAL AND CLINICAL STUDIES PERFORMED WITH Cysticlean®

Title of the studyAuthorWhereWhenPatients nºConclusionsPublished
Concentration-Dependent Effect on Adherence of Escherichia Coli to Bladder Epithelial Cells of Cysticlean® Capsules (240 Mg/Capsule of Proanthocyanidins)E Risco Rodríguez et al.Harlan, Egara, Spain2015Pre-clinicalCYS capsules (240 mg/capsule of PACs) induces a dose-dependent significant decrease in the number of E. coli adhered. Previous clinical assays showed that CYS is a product highly recommended in the prophylaxis and treatment of UTIs. The present study confirms that number of PACs is very important to achieve greatest effectiveness of the cranberry productsThe Internet Journal of Microbiology.
2015 Volume 13 Number 1.
DOI: 10.5580/IJMB.33094
Evaluation of Cysticlean® capsules, a cranberry extract with high
anti-adhesion activity, as monotherapy in uncomplicated cystitis: an observational pilot study
Isidre Bonet et al.Clinic Diagonal, Barcelona, Spain20153021 patients were successfully cured with CYS treatment only (70%) and 9 patients needed antibiotic to cure their UC. 82.35% of women and 53.,85% of men did not need antibiotic to be curedRev Electron
Biomed / Electron J
Biomed 2015;2
Treatment of pediatric urinary infections with American cranberry extractJ.M. Garat BarredoPediatric Urology Unit.
Fundacio Puigvert.
Barcelona, Spain
201162 children100% prevention of acute pyelonephritis, and 92% absence of symptomatic infections after 1y treatment Acta Pediátrica Española. 2011; 69(3): 117-120
Proanthocyanidins American cranberry extract as an alternative to antibiotic prophylaxis in pediatric patients with lower urinary tract malfunctionMartin- To be published Crespo RM et al.Uro-pediatric. Depart- at Toledo Hospital Complex, Spain2015101 children97,07% did not had an infection after 1 y treatment with Cysticlean. Only 2,97 % of patients (3 patients) suffered of episodes of UTI. One case has vesicostomy, one neurogenic bladder and the other dysfunctional voiding. Antibiotic prophylaxis was re-established in these patients. Pseudomona aeruginosa was found in 2 patients and Escherichia coli in one. The adhesion to PAC treatment was 100% and no cases of adverse events, side effect or intolerance were reportedTo be published
High Proanthocyanidins American Cranberry Extract in Pediatric
Urology: An Efficacy and Tolerability study
Miguélez Lago, Carlos et al.Hosp. Clinic Santa Elena, Málaga, Spain201174 children90% of patients did not had a UTI during the treatment period, 6,6% of patients had less UTI than before to start CYS treatment and UTI infection rate did not change in 3,3% of patients. No adverse events/side effects related to CYS were reportedTo be published
Cranberries in The Treatment of Cystitis. An Observational StudyIsidre Bonet et al.Clinic Diagonal, Barcelona, Spain201883Administering a cranberry extract with a high PAC content during a 3-month period to patients with recurrent UTI coincided with a noticeable decrease (>90%) in the usual re-incidence rate of these infectionsUrol Integr Invest 2008;13(3):214-217
Observational study of using American cranberry extract rich in proanthocyanidins (Cysticlean®) to treat recurrent urinary tract infectionsA. Collado, et al.Institut Valenciano de Oncologia
(IVO), Valencia, Spain
200978The 3-month long course of CYS in patients with recurrent infections was proven to be a well-tolerated treatment, showing a very low rate of re-infections (14%) compared to the previous reportsUrol Integr Invest 2008;13(3):214-217
Cysticlean®, a highly PAC standardized content in the prevention of
recurrent urinary tract infections: an observational, prospective, cohort study (Postcoital infections PCUTI)
Francisco Sánchez Ballester, et al.Hospital General de Valencia, Spain201320The number of PCUTI in the previous 3 m prior to start CYS treatment was 2,8 ±1,3 and it was reduced at 0,2±0,5 at month 6 (p<0,0001), which represents a 93% improvingBMC Urology 2013, 13:28 DOI:10.1186/1471- 2490-13-28
Cysticlean and Prophylaxis of Recurrent Urinary Tract Infections: Is the age a limiting factor?Fernando Rodríguez Escovar, et al.CYMA, Barcelona, Spain2016161No significant differences were found between groups A and B re reinfection rate at 3 weeks of CYS treatment (A=9,1%; B=10,6%) and at 3 m (A=11,8%;B=5,9%). Symptoms were more frequent in group B but only microhematuria was statistically significantly higher in this group compare to group A (p<0,05). Number of patients without reinfection at 3 m treated with CYS was similar in both groups. Revista Médica Electrónica Portales
médicos.com ISSN 1886-8924
Clinical Evaluation of a Cranberry Extract in the Treatment of Recurrent Cystitis in Patients over 70 y old. The GerHogar Cysticlean® Study. A Prospective Observational StudyJ. Macías, et alGerhogar, University of Salamanca, Spain201816031 of 38 patients of the group 1 treated for 1 m were successfully treated with CYS and 100 patients of 122 of the group 2 were successfully treated and followed up to 10 m. (81,57% and 81,96% respectively). Low glomerular filtration rate and high HUGE score suggest higher risk of re-infection in females than malesSubmitted
Uncomplicated Cystitis Treated with High Proanthocyanidins Cranberry Concentration in Patients Aged 70 years old and below with Recurrent Urinary Tract InfectionsJesús-José Cuadrado Blanco, et al.Gerhogar, University of Salamanca, Spain20182721 patients (78%) did not have any urinary infection along the study period. 4 males and 2
females had one. Neither non-infected patients nor infected patients showed any significant difference on its Glomerular Filtration rate, eGlomerular Filtration rate, Blood Creatinine, Blood urea and Huge before and after the treatment
Submitted

Abstarct

CONCENTRATION-DEPENDENT EFFECT ON ADHERENCE OF ESCHERICHIA COLI TO BLADDER EPITHELIAL CELLS OF Cysticlean® CAPSULES (240 MG/CAPSULE OF PROANTHOCYANIDINS)

E Risco Rodríguez, L A Álvarez-Sala Walther, V C
Ramos, I Bonet
The Internet Journal of Microbiology. 2015 Volume
13 Number 1.
DOI: 10.5580/IJMB.33094

Abstract

Background: the proanthocyanidins (PACs) are the main components of cranberry (fruit of Vaccinium macrocarpon Aiton), and their content determines the effectiveness in the urinary tract infections (UTIs). The activity of PACS is related to inhibition of bacterial adherence. Cysticlean® (CYS) is a cranberry extract product with a high quantity of PACs (240 mg/capsule of PACs). CYS is used in the prevention and treatment of recurrent UTIs. The aim of this study is the comparison of different concentrations of CYS capsules on adherence of Escherichia coli to bladder epithelial cells.

Methods: In vitro, E. coli pre-incubated in different concentrations of CYS capsules was incubated with human urinary bladder carcinoma cells (T24 cells) for 1 hour and the number of bacteria adhered to cells was recorded.

Results: CYS has demonstrated a dose-dependent inhibition of bacterial adherence. At concentrations of 5, 25, 75 and 137 mg PACs/mL, CYS decreases the number of bacteria adhered to epithelial cells by 17%, 52%, 76 and 89%, respectively.

Conclusions: CYS capsules (240 mg/capsule of PACs) induces a dose-dependent significant decrease in the number of E. coli adhered. Previous clinical assays showed that CYS is a product highly recommended in the prophylaxis and treatment of UTIs. The present study confirms that number of PACs is very important to achieve greatest effectiveness of the cranberry products.

EVALUATION OF Cysticlean® CAPSULES, A CRANBERRY EXTRACT WITH HIGH ANTI-ADHESION ACTIVITY, AS MONOTHERAPY IN UNCOMPLICATED CYSTITIS: AN OBSERVATIONAL PILOT STUDY

ster Risco Rodríguez Pharm. PhD. Humberto
Suárez MD. PhD., Isidre Bonet MD. PhD., Jesús-José
Cuadrado Blanco MD. PhD.
Rev Electron Biomed / Electron J Biomed 2015;2:

SUMMARY:

Background: Cysticlean® (CYS) is a cranberry extract product with a high quantity of  proanthocyanidins (240 mg/capsule) with a significant dose-dependent anti-adhesion activity of Escherichia coli (EC) adhered to uroepithelial cells. Previous clinical assays showed that CYS is a product highly recommended in the prophylaxis and treatment of UTIs. The aim of this study is the evaluation of CYS as an alternative to antibiotics to treat uncomplicated cystitis.

Material and Methods: This observational study included 30 consecutive ambulatory patients (17 women and 13 men), who were diagnosed of uncomplicated cystitis (UC) and agreed to participate  in this observational study. Patients were informed to come to visit the doctor again  after 15 days after CYS treatment was started (1 capsule of CYS every 12 h daily) and immediately if signs/symptoms did not disappear. In this case, CYS® was stopped and patients treated with  antibiotic.

Results: 21 patients were successfully cured with CYS treatment only (70%) and 9 patients needed antibiotic to cure their UC. 82.35% of women and 53.,85% of men did not need antibiotic to be cured. No significant differences at baseline were found regarding signs/symptoms severity between those patients cured with extract alone and those who needed antibiotic. No side effects/adverse reactions were reported.

Conclusions: These preliminary data strongly suggest that CYS could be considered as an  alternative to antibiotics for a 1st line treatment of UC. Further clinical studies to confirm whether CYS could be an alternative to antibiotic treatment for UC and this approach could contribute to reduce world-wide growing antibiotic resistance.

TREATMENT OF PEDIATRIC URINARY INFECTIONS WITH AMERICAN CRANBERRY EXTRACT.

J.M. Garat Barredo
Pediatric Urology Unit. Fundacio Puigvert.
Barcelona, Spain
Acta Pediátrica Española. 2011; 69(3): 117-120

Abstract

Introduction: In our search for alternatives to antibiotic chemoprophylaxis to prevent pediatric
urinary infections, we have started to use a concentrated extract (Cysticlean®) of American red
cranberries containing high concentration of proanthocyanidins., The before mentioned inhibit the adherence of P-fimbriated Escherichia coli to the urinary tract wall.

Objectives: To observe the effectiveness and tolerance of a concentrated extract of cranberries in
children with frequent urinary tract infections.

Material and methods: We selected groups of patients with frequently recurrent urinary infections, with no malformative systemic pathologies and either neuropathic bladder, lithiasis or renal failure. The observational study was conducted over one year in 62 children from 5 to 17 years old.

Results: the results were quite satis