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

Pain Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04148677
• Other study ID #: M1-2019
• Status: Not yet recruiting
• Start date: December 1, 2019
• Est. completion date: April 1, 2020

Study information

• Verified date: October 2019
• Source: Cardarelli Hospital
• Contact: Francesco Chiancone
• Phone: 00393408639711
• Email: francescok86[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: April 1, 2020
• Est. primary completion date: January 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Bladder Cancer
• LUTS
• Pain
• Urinary Bladder Neoplasms

Intervention

Dietary Supplement:
• Protoves M1®
A combination of two alkaloid, Protopine and Nuciferine (Protoves-M1 ®)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Cardarelli Hospital

References & Publications (6)

Dmochowski R. Antimuscarinic therapy in men with lower urinary tract symptoms: what is the evidence? Curr Urol Rep. 2006 Nov;7(6):462-7. Review. — View Citation

Fedurco M, Gregorová J, Šebrlová K, Kantorová J, Peš O, Baur R, Sigel E, Táborská 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. — View Citation

Sousa A, Piñeiro I, Rodríguez 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. — View Citation

Ustünes L, Laekeman GM, Gözler 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. — View Citation

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. — View Citation

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). pii: E2723. doi: 10.3390/molecules23102723. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	PPIUS	The PPIUS is a questionnaire developed to evaluate the patient perception of intensity of urgency	1 and 6 weeks
Primary	PGI-1	PGI-I is a validated tool to estimate the improvement or the deterioration associated to the treatment.	1 and 6 weeks
Primary	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	Qmax	Qmax (ml/s) is the maximum flow rate at uroflowmetry	1 and 6 weeks
Secondary	Volume voided	Volume voided (ml) at uroflowmetry	1 and 6 weeks
Secondary	RPM	Post-Void residual (ml) measures the amount of urine left in the bladder after urination.	1 and 6 weeks