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

February 28, 2023 updated by: Giellepi S.p.A

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed 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?

Study Type

Interventional

Enrollment (Anticipated)

80

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Romania
    • Salaj
      • Zalău, Salaj, Romania
        • SC Salvosan Ciobanca SRL

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Men or women aged ≥ 18 and ≤ 60 years. The sex will be balanced by randomized stratification.
  2. Patients diagnosed with Grade I - II symptomatic haemorrhoids (according to Goligher classification) confirmed by clinical and anoscopic or proctoscopic examination performed within 3 months before baseline. Ultrasound examination at baseline is recommended, but not mandatory.
  3. Patient free from the following treatments for haemorrhoids from at least 4 weeks: laser treatments for haemorrhoids, steroidal or non-steroidal anti-inflammatory drugs, analgesics (other than the rescue medicine indicated in the protocol), any anti-hemorrhoidal treatment (included phlebotonic compounds both drugs and dietary supplements), anticoagulants, and antiplatelet agents.
  4. Able to communicate adequately with the Investigator and to comply with the requirements for the entire study.
  5. Capable of and freely willing to provide written informed consent prior to participating in the study.

Exclusion Criteria:

  1. Inflammatory and infectious disease of the digestive tract (e.g., IBD - Inflammatory Bowel Diseases).
  2. Acute haemorrhoids or complicated haemorrhoids with bleeding requiring admission, such as strangulated internal haemorrhoids, thrombosed internal or external haemorrhoids.
  3. Previous haemorrhoidectomy or previous laser treatment.
  4. Moderate to severe hypertension, cardiovascular diseases, renal failure, cirrhosis, colorectal cancer, anal fissure or fistula.
  5. Use of laser treatments for haemorrhoids, steroidal or non-steroidal anti-inflammatory drugs, analgesics (other than the rescue medicine indicated in the protocol), any anti-hemorrhoidal treatment (included phlebotonic compounds both drugs and dietary supplements), anticoagulants, and antiplatelet agents in the 4 weeks prior to inclusion and during the whole study.
  6. Alcohol or drug abuse.
  7. Patients considered smokers (≥10 cigarettes/day).
  8. Energy-restricted diet for weight loss.

  9. Pregnant woman, lactating woman, and woman of childbearing potential who is planning a pregnancy or is unwilling to use appropriate methods of contraception* during the study.

    *Methods of contraception: hormonal contraceptive, intrauterine device or intrauterine system, double barrier method (condom with spermicide/diaphragm or cervical cap with spermicide), surgical sterilization (vasectomy, tubal ligation, etc.).

  10. Hypersensitivity to active principle (diosmin) or to any other ingredient contained in the tested food supplement.
  11. History of anaphylaxis or severe complicated allergy symptoms.
  12. Patients unlikely to cooperate.
  13. Patients with any other medical condition that, in the opinion of the Investigator, would compromise participation or be likely to lead to hospitalisation during the study.
  14. Participation in an interventional clinical study or administration of any investigational agents in the previous 30 days.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo

Investigational food supplement placebo will be administered according to the same schedule provided for the active product:

  • From day 1 to day 4: 1 tablet three times a day, before meals (breakfast, lunch and dinner)
  • From day 5 to day 7: 1 tablet twice a day, before breakfast and dinner
  • From day 8 to day 62: 1 tablet once a day, before breakfast
Other: Placebo
Use as comparator
Experimental: Experimental

The dosage will be the following:

  • From day 1 to day 4: 1 tablet three times a day, before meals (breakfast, lunch and dinner)
  • From day 5 to day 7: 1 tablet twice a day, before breakfast and dinner
  • From day 8 to day 62: 1 tablet once a day, before breakfast
Dietary supplement: diosmin and micronized flavonoids
the symptomatic treatment of haemorrhoids
Other Names:
  • MICROSMIN® PLUS

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To evaluate the efficacy of the tested food supplement Microsmin® Plus
Time Frame: 63 days
Evaluate the efficacy of the tested food supplement Microsmin® Plus (diosmin and micronized flavonoids) in comparison with placebo in the symptomatic treatment of haemorrhoids in adult patients affected by Grade I-II (Goligher classification) haemorrhoids as assessed by the patient at the end of the treatment period.
63 days
To evaluate the safety of the tested food supplement through adverse events and serious adverse events incidence assessed by Investigators and reported according to the current legislation
Time Frame: 63 days
To evaluate the safety of the tested food supplement through AE and SAE incidence assessed by Investigators and reported according to the current legislation.
63 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To evaluate the early efficacy of the tested food supplement in comparison with placebo in the symptomatic treatment of haemorrhoids as assessed by the patient after 4 and 7 days of treatment
Time Frame: 63 days
To evaluate the early efficacy of the tested food supplement in comparison with placebo in the symptomatic treatment of haemorrhoids as assessed by the patient after 4 and 7 days of treatment.
63 days
To evaluate the efficacy of the tested food supplement in comparison with placebo in the clinical improvement of haemorrhoids as assessed by the Investigator at each visit (day 7 and 63)
Time Frame: 63 days
To evaluate the efficacy of the tested food supplement in comparison with placebo in the clinical improvement of haemorrhoids as assessed by the Investigator at each visit (days 7 and 63).
63 days
To evaluate analgesic consumption in patients treated with the tested food supplement in comparison with placebo as reported by the patient in the diary
Time Frame: 63 days
To evaluate analgesic consumption in patients treated with the tested food supplement in comparison with placebo as reported by the patient in the diary.
63 days
To assess the overall satisfaction with the tested food supplement in comparison with placebo according to patient's judgement, at the end of the treatment period (day 63)
Time Frame: 63 days
To assess the overall satisfaction with the tested food supplement in comparison with placebo according to patient's judgement, at the end of the treatment period (day 63).
63 days
To assess the improvement in the quality of life by means of the Short Heath Scale for Hemorrhoidal Disease (SHSHD) score; assessed by patients after 7 and 63 days of treatment
Time Frame: 63 days
To assess the improvement in the quality of life by means of the Short Heath Scale for Hemorrhoidal Disease (SHSHD) score; assessed by patients after 7 and 63 days of treatment.
63 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Giellepi S.p.A

Collaborators

Opera CRO, a TIGERMED Group Company

Investigators

  • Study Director: Fabio Terruzzi, CSO, Giellepi S.p.A

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

February 28, 2023

Primary Completion (Anticipated)

October 15, 2023

Study Completion (Anticipated)

December 30, 2023

Study Registration Dates

First Submitted

February 14, 2023

First Submitted That Met QC Criteria

February 28, 2023

First Posted (Actual)

March 1, 2023

Study Record Updates

Last Update Posted (Actual)

March 1, 2023

Last Update Submitted That Met QC Criteria

February 28, 2023

Last Verified

February 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OPGIE/0122/FS

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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