Effect of Honey For CIN II (HoneyForCINII)

The Effect of Medical Grade Honey (L-Mesitran) for Cervical Intraepithelial Neoplasia-II

The following hypothesis is tested: Medical grade honey in CIN II causes a higher clearance of the hr-HPV virus and an increase in the normalization of CIN II lesions compared to expectant management.

Study Overview

• Status: Recruiting
• Conditions: Cervical Intraepithelial Neoplasia-II; High Risk Human Papillomavirus
• Intervention / Treatment: Drug: Medical grade honey formulation (MGH) (L-Mesitran®)

Detailed Description

In this pilot study, we will include 60 patients with newly diagnosed CIN II. Patients will be counseled according to standard guidelines between a LLETZ, imiquimod or expectant management. Patients choosing for expectant management will be asked to participate in the study and will be treated with medical grade honey. Patients choosing for expectant management but not participating in the study and thus not using medicinal honey will be asked for the control arm. Follow-up assessment takes place in accordance with the national guideline (first check-up is after 6 months). In addition, swabs for vaginal microbiota analysis will be taken at 0 and 6 months. Immunohistochemical stainings for the local immune infiltrate will be performed on biopsies taken during regular colposcopy at t=0. This exploratory study aims to investigate if there is a potential effect of honey and provides insight into its mechanisms of action.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Jordy Mongula, dr.; Phone Number: 19264 +31621872080; Email: j.mongula@zuyderland.nl
• Study Contact Backup: Name: Jasmijn Prop, Drs.; Phone Number: +31524787337; Email: j.prop@zuyderland.nl

Study Locations

• Netherlands
  • Limburg
    • Heerlen, Limburg, Netherlands, 6149 PC
      • Recruiting
      • Zuyderland MC
      • Contact: Jordy Mongula, Doctor; Phone Number: +31621872080; Email: j.mongula@zuyderland.nl
      • Contact: Jasmijn Prop, Master of Science (medicine); Phone Number: +3624787337; Email: j.prop@zuyderland.nl
      • Principal Investigator: Jordy Mongula, Doctor
    • Maastricht, Limburg, Netherlands, 6229 HX
      • Not yet recruiting
      • Maastricht University Medical Centre+
      • Contact: Peggy De Vos - van Steenwijk, Doctor; Phone Number: +31641240628; Email: peggy.de.vosvansteenwijk@mumc.nl
      • Contact: Jasmijn Prop, Master in Science; Phone Number: +31624787337; Email: j.prop@zuyderland.nl
      • Sub-Investigator: Jasmijn Prop, Master in Science

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Women 18-40 years
• Primary CIN II confirmed histologically in the biopsy on colposcopic examination
• Sufficient mastery of the Dutch language

Exclusion Criteria:

• Simultaneous abnormality in columnar epithelial cells (AIS).
• Hr-HPV negative cytology
• Immunosuppressant use/Autoimmune disease (HIV, CVID)
• History of cervical carcinoma or previous treatment for CIN (LLETZ or imiquimod)
• Pregnancy or the intention to become pregnant during the study period
• Legal incompetence
• Known allergies to honey

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Medical grade honey formulation (MGH) (L-Mesitran®) for CIN II; Daily application of 5 grams (with applicator) for 3 months. Then weekly application (5 grams with applicator) for 3 months.	Drug: Medical grade honey formulation (MGH) (L-Mesitran®); Daily application of 5 grams (with applicator) for the first 3 months, followed by weekly application of 5 grams for the following 3 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clearance of hr-HPV	The following hypothesis is tested: Medical grade honey in CIN II causes a higher clearance of the hr-HPV virus	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characteristics of the vaginal microbiome	Species specific and diversity analysis, changes due to honey and relationship with the other outcomes measures	0-6 months
Regression of CIN II	Defined as a regression to Pap 1	12-24 months
Clearance of hr-HPV and normalization of cytology (KOPAC)	Normalization of cytology (KOPAC) (depending on NVOG/RIVM flowchart).	12-24 months
Cervical immune status	Immunohistochemical stains on colposcopy biopsies for T and Myeloid cells	0 months
Human vaginal gene expression profiles	RNA quantity and quality of 20 patients	0 and 6 months
Quality of life, side-effects and compliance with medical grade honey		0, 6, 12 and 24 months

Collaborators and Investigators

• Sponsor: Zuyderland Medisch Centrum

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: January 11, 2024
• First Submitted That Met QC Criteria: January 11, 2024
• First Posted (Actual): January 23, 2024

Study Record Updates

• Last Update Posted (Actual): June 18, 2025
• Last Update Submitted That Met QC Criteria: June 13, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Honey CINII
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Uterine Diseases; Genital Diseases, Female; Neoplasms, Glandular and Epithelial; Carcinoma; Precancerous Conditions; Uterine Cervical Diseases; Neoplasms; Carcinoma in Situ; Uterine Cervical Dysplasia
• Other Study ID Numbers: NL86044.096.23

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified participant data will be shared.
• IPD Sharing Time Frame: Data will be available after publication of results.
• IPD Sharing Access Criteria: The data sharing plan includes that data (deidentified participant data) is available upon reasonable request from the corresponding author. This data could be used for further research or a meta-analysis on the use of medical grade honey for CIN II lesions. Data will be available after publication of results. Data can be available from the corresponding author J.N.M.M. Prop (https://orcid.org/0009-0009-8506-5797).'
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No