Randomised, Double-blind, Placebo-controlled to Assess the Efficacy and Safety of the Food Supplement Microsmin® Plus

Haemorrhoids Clinical Trial

Official title: Randomised, Double-blind, Placebo-controlled, Parallel-group, Multicentre, Interventional Clinical Trial to Assess the Efficacy and Safety of the Food Supplement Microsmin® Plus in the Symptomatic Treatment of Haemorrhoids

Status Not yet recruiting

Clinical Trial Summary

Haemorrhoids are variceal dilatations of the anal and perianal venous plexus and often develop secondary to the persistently elevated venous pressure within the haemorrhoidal plexus .

The classical position of haemorrhoids corresponds to three positions which are the right anterior, right posterior and the left lateral areas of the anal canal. Haemorrhoids may be external or internal. External haemorrhoids are covered with skin and internal haemorrhoids are covered with anal mucous membranes. The grading system used by Banov to classify internal haemorrhoids is one of the most common grading systems used by clinicians and is used to guide therapeutic practice. Internal haemorrhoids can be divided into four categories depending on the degree of prolapse (the protrusion of the haemorrhoid through the anus). The most widely accepted classification is the Goligher classification:

• Bleeding but no prolapse (grade I).

• Hemorrhoidal piles prolapse through the anus during straining, but they reduce spontaneously (grade II).

• Hemorrhoidal piles prolapse through the anus during straining and require manual reduction (grade III).

• The prolapse is irreducible (grade IV). Most symptoms and signs which patients present with arise from internal haemorrhoids, derive from structural changes of the normal anatomic padding (enlarged internal haemorrhoids) and are generally associated with chronic straining either due to constipation, diarrhoea or prolonged periods trying to defecate. They are also common during pregnancy and childbirth.

Clinical Trial Description

Haemorrhoids are variceal dilatations of the anal and perianal venous plexus and often develop secondary to the persistently elevated venous pressure within the haemorrhoidal plexus .

The classical position of haemorrhoids corresponds to three positions which are the right anterior, right posterior and the left lateral areas of the anal canal. Haemorrhoids may be external or internal. External haemorrhoids are covered with skin and internal haemorrhoids are covered with anal mucous membranes. The grading system used by Banov to classify internal haemorrhoids is one of the most common grading systems used by clinicians and is used to guide therapeutic practice. Internal haemorrhoids can be divided into four categories depending on the degree of prolapse (the protrusion of the haemorrhoid through the anus). The most widely accepted classification is the Goligher classification :

• Bleeding but no prolapse (grade I).

• Hemorrhoidal piles prolapse through the anus during straining, but they reduce spontaneously (grade II).

• Hemorrhoidal piles prolapse through the anus during straining and require manual reduction (grade III).

• The prolapse is irreducible (grade IV). Most symptoms and signs which patients present with arise from internal haemorrhoids, derive from structural changes of the normal anatomic padding (enlarged internal haemorrhoids) and are generally associated with chronic straining either due to constipation, diarrhoea or prolonged periods trying to defecate. They are also common during pregnancy and childbirth.

The acute clinical manifestation of the hemorrhoidal disease (commonly known as "hemorrhoidal crisis") is characterized by symptoms and signs, also common in chronic pathologies, such as rectal bleeding, prolapse, pruritus (itching), pain, oedema, often thrombosis, and less frequently soiling or mucoid discharge. Rectal bleeding (the most common presenting sign) is classically bright red as there is a high blood oxygen content within the arteriovenous anastomosis. This bleeding is usually described as bright red spotting on the toilet tissue or dripping in the toilet bowl and normally occurs at the end of defecation, separately from the stool. External haemorrhoids may be asymptomatic or associated with discomfort or with acute extreme pain in the event of a local thrombosis (formation of a clot).

Phlebotonics are a heterogenous class of drugs consisting of plant extracts (i.e., flavonoids) and synthetic compounds. Although their precise mechanism of action has not been fully established, they are known to strengthen blood vessel walls, improve venous tone, stabilise capillary permeability and increase lymphatic drainage. They have been used to treat a variety of conditions including chronic venous insufficiency, lymphoedema and haemorrhoids. In particular, numerous trials assessing the effect of phlebotonics in treating the symptoms and signs of haemorrhoidal disease (they are generally used in the less severe stages of haemorrhoids, first and second-grade haemorrhoids and during the thrombosis episodes) suggest that there is a potential benefit. Moreover, 2 reviews and 1 systematic review evaluated the micronized purified flavonoid fraction (MPFF) activities and performance in haemorrhoids.

Based on the available clinical evidence, current national guidelines and extensive clinical experience in treating patients affected by the haemorrhoidal disease, MPFF can be administered as a first-line treatment, in combination with diet (increased fibre and fluid intake) and lifestyle modifications, for acute grade I/II HD.

A new micronized formulation of diosmin was incorporated in a new dietary supplement called Microsmin® Plus to increase plasma concentrations due to the property manufacturing process able to improve intestinal absorption following oral intake. This product has evidenced a better bioavailability compared with micronized diosmin in rats (4-fold increased) and in healthy volunteers (19) (9.4 greater with higher plasmatic concentrations).

Moreover, a randomized, double-blind, placebo-controlled trial carried out in patients with chronic venous disease (CVD) showed that the administration of a low dose of Microsmin® Plus is safe and effective in relieving symptoms and improving QoL in patients with CVD after 8 weeks of treatment.

This study aims to investigate the efficacy and safety of phlebotonics (dietary supplement containing micronized diosmin, i.e., Microsmin® Plus) in alleviating the signs, symptoms and severity of haemorrhoidal disease in a set of standard clinical practices where the administration of phlebotonics is integrated with lifestyle counselling. Therefore, the Research Question of the present trial is the following: in a population of adult patients, men and women, suffering from symptomatic haemorrhoids, will the administration of the dietary supplement Microsmin® Plus (diosmin and micronized flavonoids) for 63 days (7-days acute treatment phase + 55-days maintenance phase), integrated with lifestyle counselling, improve the symptomatology (clinical signs and symptoms) in comparison with patients receiving placebo, results observed after 4, 7 and 63 days after the beginning of the treatment? ;

Related Conditions & MeSH terms

• Haemorrhoids
• Hemorrhoids

• NCT number: NCT05750563
• Study type: Interventional
• Source: Giellepi S.p.A
• Contact: Dionisio F. Barattini, MD
• Phone: +39 3355437574
• Email: barattini@operacro.com
• Status: Not yet recruiting
• Phase: N/A
• Start date: February 28, 2023
• Completion date: December 30, 2023