Effects of a Food Supplement in the Prevention of Urinary Tract Infections in Kidney Transplant Patients.

Study Overview
=================
Brief Summary
-----------------
The incidence of Urinary tract infections (UTIs) is very high in kidney transplant patients. Most UTIs occur during the first six months (82% within the first three months) of kidney transplantation and are frequently recurrent. The component D-mannose of our authorized food supplement acts by inhibiting the adherence of E.coli to the urothelium. It also has a controlled release formula that ensures the presence in urine of D-mannose and the other components during 24 hours. This is the reason why this experimental study aims to demonstrate that the oral intake of this food supplement is effective in the prevention of UTIs in kidney transplant patients.

Detailed Description
-----------------
The study tries to analyze the impact of a food supplement (Manosar®) on the incidence of urinary infections in patients undergoing kidney transplantation. The patients will be randomly distributed (1: 1 ratio) into two treatment groups of 30 patients each. In one group, they will be treated with Manosar®, and in the other group they will be treated with Proanthocyanidins. All patients will be followed for 6 months, being the first three months of the study drug administration. This experimental study is double-blinded and there are 7 monthly study visits. Properties of D-mannose and Proanthocyanidins make interesting to evaluate the clinical benefit of the use of food supplements with D-mannose and Proanthocyanidins in order to prevent the UTIs without antibiotics.

Official Title
-----------------
Study of a Food Supplement (Mannose and Proanthocyanidins Prolonged Release 24h) Versus Proanthocyanidins in the Prevention of Urinary Tract Infections in Kidney Transplant Patients.

Conditions
-----------------
Kidney Transplant Infection

Intervention / Treatment
-----------------
* Dietary Supplement: MANOSAR®
* Dietary Supplement: Proanthocyanidins


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: ≥ 18 years. Recipients of a cadaveric donor kidney transplant. Patients who are trained to give their informed consent. Exclusion Criteria: Recipients of a kidney transplant who do not authorize their participation in the study by informed consent. Recipients of a transplant of an organ other than the kidney. Patients with Bricker or Studer neobladders. Patients in need of intermittent self-catheterization prior to kidney transplantation. Any medical, psychiatric or family condition that, in the opinion of the investigator, may endanger or compromise the patient's ability to participate in the study. Pregnant or lactating patients. Having participated in clinical trials in the previous 3 months or participating in another clinical study promoted by the pharmaceutical industry, in which the promoter already establishes the treatment for UTI.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Food supplement<br>MANOSAR® is an authorized food supplement that contains D-mannose, Proanthocyanidins, Ursolic Acis, vitamin complexes and ions, and protects against urinary tract infections. | Dietary Supplement: MANOSAR®<br>* MANOSAR® is an authorized food supplement that contains D-mannose, Proanthocyanidins, Ursolic Acis, vitamin complexes and ions, and protects against urinary tract infections.<br>* Other names: Food Supplement;|
| Active Comparator: Comparator<br>The comparator are Proanthocyanidins of continuous-release, which are isolated from cranberry, and prevents the adhesion of uropathogenic bacteria such a E.coli to the wall of the urothelium. | Dietary Supplement: Proanthocyanidins<br>* The comparator are Proanthocyanidins of continuous-release, which are isolated from cranberry, and prevents the adhesion of uropathogenic bacteria such a E.coli to the wall of the urothelium.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change on the incidence of urinary tract infections. | To assess the magnitude of the change from baseline incidence of urinary tract infections in kidney transplant patients at one month, two months and three months of treatment and at four, five and six months of follow-up. | Baseline to 1, 2, 3, 4, 5 and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of three types of urinary tract infection: asymptomatic bacteriuria, cystitis, and pyelonephritis between both treatment groups. | All information regarding these infections will be recorded. | Baseline to all study visits up to 6 months. | 
| Rate of urinary tract infections caused by E.coli. | E. coli will be assessed by urine cultures, which are performed according to the usual clinical practice of the site (weekly - from Visit 0 to Visit 1 (4 urine cultures); fortnightly - from Visit 1 to Visit 3 (4 urine cultures); monthly - from Visit 3 to Visit 6 (3 urine cultures)). Also if there is suspected infection based on clinical criteria there will be performed also an urine culture. | Baseline to all study visits up to 6 months. | 
| Rate of patients who developed bacteremia during the episode of pyelonephritis. | This will be assessed in relation to the performance of urine cultures. | Baseline to all study visits up to 6 months. | 
| Rate of safety episodes between both treatment groups. | All episodes will be recorded, whether considered minor or serious, drug-related or not. | From Visit 1, and at each visit, up to 6 months. | 
| Rate of incidence of delayed renal graft function. | This is assessed by the need for a hemodialysis session. | From Visit 0 to Visit 1, up to 1 month. | 
| Change from baseline in both treatment groups of concentration of glucose in renal function. | The concentration of glucose (mmol/L) is assessed by the value results of the laboratory analysis, which are completed according to the usual clinical practice of the site for the follow-up of kidney transplant patients: weekly - from Visit 0 to Visit 1 (4 tests); fortnightly - from Visit 1 to Visit 3 (4 tests); monthly - from Visit 3 to Visit 6 (3 tests). | Baseline to all study visits up to 6 months. | 
| Rate of histologically confirmed acute rejection and number of patients who lost the kidney graft. | Assessed during the 6 months study. | Baseline to all study visits up to 6 months. | 
| Rate of bacterial colonization of the double J catheter in both treatment groups. | This is assessed by the microbiological analysis of the tips of the double J catheter will be performed between Visit 0 and Visit 1, once it has been removed 21-27 days after kidney transplantation. | From Visit 0 to Visit 1, up to 1 month. | 
| Type of bacterial colonies of the double J catheter | This is assessed by the microbiological analysis of the tips of the double J catheter will be performed between Visit 0 and Visit 1, once it has been removed 21-27 days after kidney transplantation. | From Visit 0 to Visit 1, up to 1 month. | 
| Change from baseline in both treatment groups of concentration of Glomerular Filtration Rate (GFR). | The calculation of GFR (ml/min) is estimated with a blood test, which is completed according to the usual clinical practice of the site for the follow-up of kidney transplant patients: weekly - from Visit 0 to Visit 1 (4 tests); fortnightly - from Visit 1 to Visit 3 (4 tests); monthly - from Visit 3 to Visit 6 (3 tests). | Baseline to all study visits up to 6 months. | 
| Change from baseline in both treatment groups of concentration of serum creatinine in renal function. | The concentration of serum creatinine (µmol/L) is assessed by the value results of the laboratory analysis, which are completed according to the usual clinical practice of the site for the follow-up of kidney transplant patients: weekly - from Visit 0 to Visit 1 (4 tests); fortnightly - from Visit 1 to Visit 3 (4 tests); monthly - from Visit 3 to Visit 6 (3 tests). | Baseline to all study visits up to 6 months. | 
| Change from baseline in both treatment groups of concentration of sodium in renal function. | The concentration of sodium (mEq/L) is assessed by the value results of the laboratory analysis, which are completed according to the usual clinical practice of the site for the follow-up of kidney transplant patients: weekly - from Visit 0 to Visit 1 (4 tests); fortnightly - from Visit 1 to Visit 3 (4 tests); monthly - from Visit 3 to Visit 6 (3 tests). | Baseline to all study visits up to 6 months. | 
| Change from baseline in both treatment groups of concentration of potassium in renal function. | The concentration of potassium (mEq/L) is assessed by the value results of the laboratory analysis, which are completed according to the usual clinical practice of the site for the follow-up of kidney transplant patients: weekly - from Visit 0 to Visit 1 (4 tests); fortnightly - from Visit 1 to Visit 3 (4 tests); monthly - from Visit 3 to Visit 6 (3 tests). | Baseline to all study visits up to 6 months. |