Efficacy and Safety Evaluation of Ruscus Aculeatus L in Patients With Hemorrhoids

Official title

Efficacy and Safety Evaluation of Ruscus Aculeatus L in Patients With Hemorrhoids: A Randomized, Double-blind Phase IV Clinical Trial

Overview

Hemorrhoidal disease is characterized by distal displacement and deterioration of structural integrity of vascular cushions in the anal canal, which physiologically help defecation and continence. Unlike advanced stage (stage IV) hemorrhoids, which require surgical intervention, various topical agents (gels, ointments, creams), oral venoactive drugs, homeopathic and phytotherapeutic products and nutritional supplements are widely used in stage II and III hemorrhoidal disease. The genus Ruscus (family Asparagaceae) is a group of plants native to the Mediterranean basin, Southern and Western Europe, and Iran, represented by perennial, rhizome-based, and evergreen shrubs. Among the species belonging to this genus, Ruscus aculeatus L. has the widest distribution area. The subsoil parts of the Ruscus plant are rich in steroidal saponins and show vasoconstrictor, diuretic, anti-inflammatory and venotonic effects, especially with ruscogenin and neoruscogenin compounds. Due to these properties, R. aculeatus stands out as a traditional phytotherapy agent that has been used for a long time in chronic venous insufficiency. However, there are no controlled clinical studies in the literature evaluating the efficacy and safety of Ruscus aculeatus L. in hemorrhoidal disease. Therefore, this study was aimed to systematically evaluate the contribution of a phytotherapeutic product containing R. aculeatus to the treatment of stage II-III hemorrhoidal patients and to provide scientific evidence of a new and potentially safe herbal treatment option that can be used in the treatment of hemorrhoids.

Detailed description

The aim of this study was to evaluate the efficacy and safety of Neoven 225 mg capsule containing Ruscus aculeatus L. in individuals with stage II-III hemorrhoidal disease according to the Goligher classification.

Hemorrhoidal disease is characterized by distal displacement and deterioration of structural integrity of vascular cushions in the anal canal, which physiologically help defecation and continence. As a result, venous distension, inflammation, erosion, bleeding and thrombosis may develop in hemorrhoidal tissues.

Clinically, depending on the stage of the disease, symptoms such as bright red rectal bleeding during defecation, discomfort around the anus, itching, fecal incontinence, pain and protrusion may occur. However, uncertainty about the pharmacological treatment of hemorrhoidal disease still remains.

Unlike advanced stage (stage IV) hemorrhoids, which require surgical intervention, various topical agents (gels, ointments, creams), oral venoactive drugs, homeopathic and phytotherapeutic products and nutritional supplements are widely used in stage II and III hemorrhoidal disease. Among oral venoactive drugs, synthetic calcium dobesilate, diosmin-hesperidin combination of natural origin, triterpenes and saponins are the most well-known compounds. The genus Ruscus (family Asparagaceae) is a group of plants native to the Mediterranean basin, Southern and Western Europe, and Iran, represented by perennial, rhizome-based, and evergreen shrubs. Among the species belonging to this genus, Ruscus aculeatus L. has the widest distribution area. The subsoil parts of the Ruscus plant are rich in steroidal saponins and show vasoconstrictor, diuretic, anti-inflammatory and venotonic effects, especially with ruscogenin and neoruscogenin compounds. Due to these properties, R. aculeatus stands out as a traditional phytotherapy agent that has been used for a long time in chronic venous insufficiency.

However, there are no controlled clinical studies in the literature evaluating the efficacy and safety of Ruscus aculeatus L. in hemorrhoidal disease. Therefore, this study was aimed to systematically evaluate the contribution of a phytotherapeutic product containing R. aculeatus to the treatment of stage II-III hemorrhoidal patients and to provide scientific evidence of a new and potentially safe herbal treatment option that can be used in the treatment of hemorrhoids.

Interventions

• Drug Neoven 225 mg capsules
  Patients in this group will only use Neoven 225 mg capsules orally. There will be no signs or inscriptions on the capsules regarding their contents. The duration of the study is determined as 42 days. A total of 378 mg of total ruscogenin (ruscogenin/neoruscogenin mixture obtained by extraction method) will be taken orally using one Neoven capsule orally with meals twice a day. A total of 84 capsules will be given to the patients, and their use will be questioned by phone on the 7th and 14th day
• Drug Placebo
  Patients in this group will only receive an oral placebo capsule designed for this study. There will be no signs or inscriptions on the capsules regarding their contents. The duration of the study is determined as 42 days. During this period, one placebo capsule will be taken orally twice a day with meals. A total of 84 capsules will be given to the patients, and their use will be questioned by phone on the 7th and 14th days of the treatment and the number of uses will be checked at the end of t

Primary outcome measures

• Quality of Life for HSS (Hemorrhoid Severity Score) [Time frame: At the end of the treatment (42nd day)]

Secondary outcome measures (2)

• Hemorrhoidal Disease Symptom Score (HHSS) [Time frame: At the end of the treatment (42nd day)]
• Visual Analog Scale (VAS) [Time frame: At the end of the treatment (42nd day)]

Eligibility criteria

Inclusion criteria

• Patients between the ages of 18-45 with complaints (symptomatic) consistent with hemorrhoidal disease
• Patients with Stage II and III hemorrhoids according to the Goligher Hemorrhoid Rating system using physical examination (digital rectal examination, anoscopy/rectoscopy performed within a maximum of four weeks before the examination)
• Patients who have signed the Informed Consent Form

Exclusion criteria

• Patients aged <18 and >45 years
• Stage I and IV hemorrhoids according to the Goligher Hemorrhoid Rating system
• Surgery for hemorrhoids at any time
• Injection treatment for multiple hemorrhoids in the last 3 years
• Perianal sepsis, inflammatory bowel disease, colorectal malignancy, or pre-existing sphincter injury within the last 3 years
• Immunodeficiency
• In addition to hemorrhoids, patients with anal fissures and perianal fistulas detected by simultaneous physical examination or anoscopy/rectoscopy

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Turkey (Türkiye) · 1 center

• Sultan Abdulhamid Training and Research Hospital — Istanbul

Publications

• Bouskela E, Cyrino FZ, Marcelon G. Effects of Ruscus extract on the internal diameter of arterioles and venules of the hamster cheek pouch microcirculation. J Cardiovasc Pharmacol. 1993 Aug;22(2):221-4. doi: 10.1097/00005344-199308000-00008. PMID 7692161
• Masullo M, Pizza C, Piacente S. Ruscus Genus: A Rich Source of Bioactive Steroidal Saponins. Planta Med. 2016 Dec;82(18):1513-1524. doi: 10.1055/s-0042-119728. Epub 2016 Nov 8. PMID 27825178
• Boyle P, Diehm C, Robertson C. Meta-analysis of clinical trials of Cyclo 3 Fort in the treatment of chronic venous insufficiency. Int Angiol. 2003 Sep;22(3):250-62. PMID 14612852
• Pompilio G, Nicolaides A, Kakkos SK, Integlia D. Systematic literature review and network Meta-analysis of sulodexide and other drugs in chronic venous disease. Phlebology. 2021 Oct;36(9):695-709. doi: 10.1177/02683555211015020. Epub 2021 May 13. PMID 33983078

Identifiers

NCT: NCT07128979 · 2024-KAEK-18

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗