Protoves M1® Syrup in Controlling Adverse Event During HIVEC® Instillations

The Role of Protopine Associated With Nuciferine (Protoves M1® Syrup) in Controlling Adverse Event During HIVEC® Instillations

100 patients with bladder cancer whose underwent Hyperthermic Intravesical Chemotherapy (HIVEC®) will be randomized in two groups (Group A: PROTOVES M1 SYRUP, Group B: NO TREATMENT). The aim of this study will be to analyse the role of two alkaloid, Protopine and Nuciferine (Protoves-M1 ®) in the prevention and the treatment of the low and mild grade adverse events related to the use of HIVEC® instillations.

Study Overview

• Status: Unknown
• Conditions: Pain; Bladder Cancer; LUTS
• Intervention / Treatment: Dietary supplement: Protoves M1®

Detailed Description

100 patients with bladder cancer whose underwent Hyperthermic Intravesical Chemotherapy (HIVEC®) will be randomized in two groups (Group A: PROTOVES M1 SYRUP, Group B: NO TREATMENT). The aim of this study will be to analyse the role of two alkaloid, Protopine and Nuciferine (Protoves-M1 ®) in the prevention and the treatment of the low and mild grade adverse events related to the use of HIVEC® instillations.

At the baseline data on demographic and anthropometric features (age, weight, height, BMI), lifestyle characteristics (smoke, alcohol), any comorbidities (hypertension, diabetes mellitus, etc.) will be collected. All patients will be undergone to a clinical evaluation (comprised general, genital and urologic examination). Before starting the treatment, the following measurements will be collected: prostate volume by transrectal ultrasound, PSA, uroflowmetry (Qmax, Volume Voided, Post-Void Residual), IPSS (International Prostatic Symptoms Score) questionnaire, OverActive Bladder questionnaire-short form (OABq-SF) 6 and 13, patient perception of intensity of urgency scale (PPIUS), and visual analogue scale (VAS). PSA and IPSS will be investigated only in male pts. In addition, the patient impression of improvement will be assessed. Improvement will be evaluated with the Patient Global Impression of Improvement questionnaire (PGI-I), a validated tool to estimate the improvement or the deterioration associated to the treatment.

The primary endpoint was the evaluation of the efficacy of the therapy with Protoves-M1 in controlling of the irritative symptoms, including nocturia, urinary frequency, bladder pain, urgency and urge incontinence related to the chemo-hyperthermia treatment. The secondary endpoint evaluated was the influences of the treatment on the uroflowmetric parameters.

After 1 and 6 weeks of therapy all patients will be undergone to a clinical and instrumental evaluation : Uroflow-Qmax (ml/s), Uroflow-Volume voided (ml),Uroflow-RPM (ml), IPSS total, OAB-q SF 6, OAB-q SF 13, PPIUS, PGI-I, VAS scale will be collected.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

All patients who referred to a general hospital to receive endoscopic treatment for bladder cancer (TURB) and then the endovescical chemioprofilaxis.

Description

Inclusion Criteria:

• Intermediate-and high-risk NMIBC (non-muscle invasive bladder cancer) patients.
• Therapeutic program of HIVEC® (Recirculant hyperthermic IntraVEsical chemotherapy).
• Must be able to drink a syrup.

Exclusion Criteria:

• Uncontrolled underlying diseases (ASA III or IV)
• Post void residual urine ≥ 100 ml
• Bleeding tendency
• Drug abuse
• Chronic pelvic pain
• Urinary tract infection
• Neurological disease
• Bladder lithiasis
• Renal or liver failure
• Tachycardia and heart failure.
• Male patients with lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH)with abnormal values of uroflowmetry
• Male patients with lower urinary tract symptoms (LUTS) that assume medical treatment for BPH.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Protoves M1® syrup; A combination of two alkaloid, Protopine and Nuciferine	Dietary supplement: Protoves M1®; A combination of two alkaloid, Protopine and Nuciferine (Protoves-M1 ®)
No treatment; Patients will not receive a treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IPSS total	The International Prostate Symptom Score (I-PSS) is based on the answers to some questions concerning urinary symptoms and one question concerning quality of life.	1 and 6 weeks
OAB-q SF 6	The OAB-q SF 6 is a questionnaire developed to evaluate the overactive bladder symptom and health-related quality of life.	1 and 6 weeks
OAB-q SF 13	The OAB-q SF 6 is a questionnaire developed to evaluate the overactive bladder symptom and health-related quality of life.	1 and 6 weeks
PPIUS	The PPIUS is a questionnaire developed to evaluate the patient perception of intensity of urgency	1 and 6 weeks
PGI-1	PGI-I is a validated tool to estimate the improvement or the deterioration associated to the treatment.	1 and 6 weeks
VAS scale	Visual analogue scales (VAS) are 10-cm lines anchored at the ends by words that define the bounds of various pain dimensions.	1 and 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Qmax	Qmax (ml/s) is the maximum flow rate at uroflowmetry	1 and 6 weeks
Volume voided	Volume voided (ml) at uroflowmetry	1 and 6 weeks
RPM	Post-Void residual (ml) measures the amount of urine left in the bladder after urination.	1 and 6 weeks

Collaborators and Investigators

• Sponsor: Cardarelli Hospital
• Investigators: Principal Investigator: Francesco Chiancone, AORN A.Cardarelli Urology Department

Publications and helpful links

General Publications

• Sousa A, Pineiro I, Rodriguez S, Aparici V, Monserrat V, Neira P, Carro E, Murias C, Uribarri C. Recirculant hyperthermic IntraVEsical chemotherapy (HIVEC) in intermediate-high-risk non-muscle-invasive bladder cancer. Int J Hyperthermia. 2016 Jun;32(4):374-80. doi: 10.3109/02656736.2016.1142618. Epub 2016 Feb 25.
• Ustunes L, Laekeman GM, Gozler B, Vlietinck AJ, Ozer A, Herman AG. In vitro study of the anticholinergic and antihistaminic activities of protopine and some derivatives. J Nat Prod. 1988 Sep-Oct;51(5):1021-2. doi: 10.1021/np50059a043. No abstract available.
• Fedurco M, Gregorova J, Sebrlova K, Kantorova J, Pes O, Baur R, Sigel E, Taborska E. Modulatory Effects of Eschscholzia californica Alkaloids on Recombinant GABAA Receptors. Biochem Res Int. 2015;2015:617620. doi: 10.1155/2015/617620. Epub 2015 Oct 5.
• Zhang C, Deng J, Liu D, Tuo X, Yu Y, Yang H, Wang N. Nuciferine Inhibits Proinflammatory Cytokines via the PPARs in LPS-Induced RAW264.7 Cells. Molecules. 2018 Oct 22;23(10):2723. doi: 10.3390/molecules23102723.
• Wang MX, Zhao XJ, Chen TY, Liu YL, Jiao RQ, Zhang JH, Ma CH, Liu JH, Pan Y, Kong LD. Nuciferine Alleviates Renal Injury by Inhibiting Inflammatory Responses in Fructose-Fed Rats. J Agric Food Chem. 2016 Oct 26;64(42):7899-7910. doi: 10.1021/acs.jafc.6b03031. Epub 2016 Oct 18.
• Dmochowski R. Antimuscarinic therapy in men with lower urinary tract symptoms: what is the evidence? Curr Urol Rep. 2006 Nov;7(6):462-7. doi: 10.1007/s11934-006-0055-4.

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2019
• Primary Completion (Anticipated): January 1, 2020
• Study Completion (Anticipated): April 1, 2020

Study Registration Dates

• First Submitted: October 25, 2019
• First Submitted That Met QC Criteria: October 30, 2019
• First Posted (Actual): November 1, 2019

Study Record Updates

• Last Update Posted (Actual): November 1, 2019
• Last Update Submitted That Met QC Criteria: October 30, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Urinary Bladder Neoplasms
• Other Study ID Numbers: M1-2019

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No