Efficacy and Safety of Renalof® in the Removal of Calculi Smaller Than 10 mm Located in the Reno-Ureteral Tract

• ClinicalTrials.gov Identifier: NCT04695951
• Recruitment Status: Completed
• First Posted: January 6, 2021
• Last Update Posted: January 6, 2021
• Sponsor: Catalysis SL
• Information provided by (Responsible Party): Catalysis SL

Study Description

Brief Summary:

Given the high recurrence of urolithiasis in patients, the search for less aggressive and preventive treatments is increasingly necessary. Renalof® is presented as an alternative to herbal medicine being a product that, due to its diuretic and demineralization properties of kidney stones, has been widely used in this patient population, disintegrating and eliminating calcium oxalate and struvite stones in a painless in the genitourinary system.

With the objective of determining the efficacy of this therapy, an observational, prospective, randomized, single-blind, two-arm study was carried out: treatment group with Renalof® and control group, placebo.

Condition or disease	Intervention/treatment	Phase
Renal Injury; Kidney Injury; Kidney Calculi; Ureteral Obstruction; Ureteral Calculi; Renal Stone; Ureteral Injury; Renal Disease; Urolithiasis, Calcium Oxalate; Urolithiasis; Lower Urinary Tract; Urolithiasis	Dietary Supplement: Renalof; Other: Placebo	Phase 2

Detailed Description:

Given the high recurrence of urolithiasis in patients, the search for less aggressive and preventive treatments is increasingly necessary. Renalof® is presented as an alternative to herbal medicine being a product that, due to its diuretic and demineralization properties of kidney stones, has been widely used in this patient population, disintegrating and eliminating calcium oxalate and struvite stones in a painless in the genitourinary system.

With the objective of determining the efficacy of this therapy, an observational, prospective, randomized, single-blind, two-arm study was carried out: treatment group with Renalof® and control group, placebo.

The treatment group consists of 120 patients over 18 years of age, of both sexes, with a diagnosis of urolithiasis less than 10 mm in diameter, present throughout the entire reno-uretero-bladder path, diagnosed by ultrasound, renal CT and urography . The Renalof® product was administered at a dose of 650 mg daily for 3 months and the presence of stones in any location of the reno-ureteral tract was evaluated using one of the diagnostic means mentioned in monthly consultations. The second group, treated with placebo corresponding to 35 people constituting 30% of the universe. The study period was from August 2019 to July 2020 at the Hospital Escuela Antonio Lenin Fonseca and the Seniors clinic, in the city of Managua, Nicaragua.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 155 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of Renalof® in the Removal of Calculi Smaller Than 10 mm Located in the Reno-Ureteral Tract
• Actual Study Start Date: August 1, 2019
• Actual Primary Completion Date: July 1, 2020
• Actual Study Completion Date: October 1, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Renalof; A total of 120 patients treated with the study product Renalof® at a dose of 650 mg twice daily were followed for 4 months. A preliminary analysis of the types of stones present in the study patients was performed according to the main compound, using a biophysical profile by biochemical analysis and the clinical characteristics, medical history and biochemical profile of the creatinine values of the test patients. Imaging and quality of life tests were carried out during the trial to check the efficacy and possible adverse effects of the test product in patients with kidney stones.	Dietary Supplement: Renalof; A total of 120 patients treated with the study product Renalof® at a dose of 650 mg twice daily were followed for 4 months. A preliminary analysis of the types of stones present in the study patients was performed according to the main compound, using a biophysical profile by biochemical analysis and the clinical characteristics, medical history and biochemical profile of the creatinine values of the test patients. Imaging and quality of life tests were carried out during the trial to check the efficacy and possible adverse effects of the test product in patients with kidney stones.
Placebo Comparator: Control; A total of 35 patients treated with the study product Placebo at a dose of 650 mg twice daily were followed for 4 months. A preliminary analysis of the types of stones present in the study patients was performed according to the main compound, using a biophysical profile by biochemical analysis and the clinical characteristics, medical history and biochemical profile of the creatinine values of the test patients. Imaging and quality of life tests were carried out during the trial to check the efficacy and possible adverse effects of the test product in patients with kidney stones.	Other: Placebo; A total of 35 patients treated with Placebo at a dose of 650 mg twice daily were followed for 4 months. A preliminary analysis of the types of stones present in the study patients was performed according to the main compound, using a biophysical profile by biochemical analysis and the clinical characteristics, medical history and biochemical profile of the creatinine values of the test patients. Imaging and quality of life tests were carried out during the trial to check the efficacy and possible adverse effects of the test product in patients with kidney stones.

Outcome Measures

Primary Outcome Measures :

1. kidney stone clearance with Renalof® treatment compared to placebo [ Time Frame: 4 months ]
   kidney stone clearance with Renalof® treatment compared to placebo measured by ultrasound and tomography imaging

Secondary Outcome Measures :

1. Quality of life of patients [ Time Frame: 4 months ]
   Quality of life was established in relation to the presence or absence of symptoms related to the disease by means of a bimonthly personal questionnaire: dysuria or burning when urinating, urinary urgency, kidney colic, difficulty in performing daily activities and periodicity of urinary infections (mild, moderate, severe, yes or no,).
2. Number of colic [ Time Frame: 4 months ]
   number of colic during the 4-month follow-up of treatment
3. Adverse events related with product of the trial [ Time Frame: 4 months ]
   Adverse effects related with the test product in patients with kidney stones, measured by means of a bimonthly personal questionnaire: nausea, vomiting, digestive pain, stomach ache... (mild, moderate, severe, yes or no,).

Other Outcome Measures:

1. Cost of treatment [ Time Frame: 4 months ]
   cost of treatment with the use of Renalof® compared to the usual treatments, taking into account hospitalization time due to the number of colic and recovery time due to urolithiasis

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Patient over 18 years of age, in all their mental and physical capacities to decide to be part of this study.
2. There are no comorbidities or associated diseases that put the stability of the patient at risk.
3. Not be diagnosed as Chronic Kidney Disease, in any stage.
4. Existence of non-obstructive stones smaller than 10 mm located in the renoureteral path.
5. No compromise of renal viability.

Exclusion Criteria:

1. Patients under 18 years of age.
2. Existence of comorbidities or associated diseases that put the stability of the patient at risk.
3. Existence of a diagnosis of Chronic Kidney Disease, at any stage.
4. Presence of non-obstructive or obstructive stones greater than 10 mm located in the renoureteral path.
5. Renal viability compromise.

Contacts and Locations

Locations

Nicaragua

Clinica Seniors Managua

Managua, Nicaragua, 13035

Sponsors and Collaborators

Catalysis SL

More Information

Publications:

Tsujihata M. Mechanism of calcium oxalate renal stone formation and renal tubular cell injury. Int J Urol. 2008 Feb;15(2):115-20. doi: 10.1111/j.1442-2042.2007.01953.x. Review.

Johnson CM, Wilson DM, O'Fallon WM, Malek RS, Kurland LT. Renal stone epidemiology: a 25-year study in Rochester, Minnesota. Kidney Int. 1979 Nov;16(5):624-31.

Soucie JM, Coates RJ, McClellan W, Austin H, Thun M. Relation between geographic variability in kidney stones prevalence and risk factors for stones. Am J Epidemiol. 1996 Mar 1;143(5):487-95.

Wesson JA, Johnson RJ, Mazzali M, Beshensky AM, Stietz S, Giachelli C, Liaw L, Alpers CE, Couser WG, Kleinman JG, Hughes J. Osteopontin is a critical inhibitor of calcium oxalate crystal formation and retention in renal tubules. J Am Soc Nephrol. 2003 Jan;14(1):139-47.

Kohri K, Yasui T, Okada A, Hirose M, Hamamoto S, Fujii Y, Niimi K, Taguchi K. Biomolecular mechanism of urinary stone formation involving osteopontin. Urol Res. 2012 Dec;40(6):623-37. doi: 10.1007/s00240-012-0514-y. Epub 2012 Nov 6. Review.

Mykoniatis I, Sarafidis P, Memmos D, Anastasiadis A, Dimitriadis G, Hatzichristou D. Are endourological procedures for nephrolithiasis treatment associated with renal injury? A review of potential mechanisms and novel diagnostic indexes. Clin Kidney J. 2020 May 22;13(4):531-541. doi: 10.1093/ckj/sfaa020. eCollection 2020 Aug. Review.

Grases F, Ramis M, Costa-Bauzá A, March JG. Effect of Herniaria hirsuta and Agropyron repens on calcium oxalate urolithiasis risk in rats. J Ethnopharmacol. 1995 Mar;45(3):211-4.

Beydokthi SS, Sendker J, Brandt S, Hensel A. Traditionally used medicinal plants against uncomplicated urinary tract infections: Hexadecyl coumaric acid ester from the rhizomes of Agropyron repens (L.) P. Beauv. with antiadhesive activity against uropathogenic E. coli. Fitoterapia. 2017 Mar;117:22-27. doi: 10.1016/j.fitote.2016.12.010. Epub 2016 Dec 29.

Paslawska S, Piekos R. Studies on the optimum conditions of extraction of silicon species from plants with water. IV. Agropyron repens. Planta Med. 1976 Nov;30(3):216-22.

Bragadottir G, Redfors B, Ricksten SE. Mannitol increases renal blood flow and maintains filtration fraction and oxygenation in postoperative acute kidney injury: a prospective interventional study. Crit Care. 2012 Aug 17;16(4):R159. doi: 10.1186/cc11480.

Hägerström E, Lindberg L, Bentzen J, Brødbæk K, Zerahn B, Kristensen B. The Nephroprotective Effect of Mannitol in Head and Neck Cancer Patients Receiving Cisplatin Therapy. Clin Med Insights Oncol. 2019 Jan 7;13:1179554918821320. doi: 10.1177/1179554918821320. eCollection 2019.

• Responsible Party: Catalysis SL
• ClinicalTrials.gov Identifier: NCT04695951
• Other Study ID Numbers: 201920-RENALOF-NI
• First Posted: January 6, 2021
• Last Update Posted: January 6, 2021
• Last Verified: December 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Catalysis SL:

Urolithiasis; Kidney Stone; Agropyron Repens; Ureteral calculi; Calcium oxalate

Additional relevant MeSH terms:

Urolithiasis; Urinary Calculi; Kidney Calculi; Nephrolithiasis; Ureteral Calculi; Ureterolithiasis; Ureteral Obstruction; Calculi; Wounds and Injuries; Kidney Diseases; Urologic Diseases; Pathological Conditions, Anatomical; Ureteral Diseases