Cancer Chemoprevention by Metformin Hydrochloride Compared to Placebo in Oral Potentially Malignant Lesions

Cancer Chemoprevention by Metformin Hydrochloride Compared to Placebo in Oral Potentially Malignant Lesions: A Randomised Clinical Trial

Evaluation of the metformin drug effect as a drug that found to improve the quality of tissues, decrease signs & symptoms of cancer, and decrease histo-pathological criteria of dysplasia.

This will be done by the aid of measuring salivary Micro RNA 31 & 210 in saliva in addition to measure cyclin A2 as an immuno-histochemical analysis.

Study Overview

• Status: Unknown
• Conditions: Oral Cancer
• Intervention / Treatment: Drug: Metformin Hcl 500Mg 24Hr Sa Tab; Other: starch tablet

Detailed Description

Oral squamous cell carcinomas (OSCCs) are among the most common types of head and neck cancers and are a major cause of significant morbidity. It was reported that 16- 62% of OSCCs develop from premalignant lesions, which often presents clinically as white or red mucosal patches known as leukoplakia and erythroplakia. The role of miRNA in cancer has been reiterated and established by many studies that have shown that miRNA signatures (i.e., mRNA expression profiles) can be useful for classifying human cancers. These studies have identified "cancer related miRNAs" through investigating expression profiles in matched normal and tumor tissues, as well as in body fluids. In addition, a vast number of studies have shown that miRNAs can play a role in regulating the expression of oncogenes and tumor suppressor genes, whereas others have shown that miRNA gene deletion or mutation can lead cancer initiation, progression and metastasis . Several potential mechanisms have been suggested for the ability of metformin to suppress cancer growth in vitro and vivo:

(1) Activation of LKB1/AMPK pathway, (2) Induction of cell cycle arrest and/or apoptosis, (3) Inhibition of protein synthesis, (4) Reduction in circulating insulin levels, (5) Inhibition of the unfolded protein response (UPR), (6) Activation of the immune system.

This study is performed to evaluate metformin effect on the patients premalignant lesion versus maintenace follow ups.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Noha N. El-Zalabany, Masters; Phone Number: 02 01005365769; Email: noha_nasr84@yahoo.com
• Study Contact Backup: Name: Ahmed A. Abd El-Azim, Masters; Phone Number: 02 01007975679; Email: hero_ahmed704@hotmail.com

Study Locations

• Egypt
  • New Cairo
    • Cairo, New Cairo, Egypt, 11835
      • Recruiting
      • Noha Nasr
      • Contact: Noha N. El-Zalabany, Masters; Phone Number: 02 01005365769; Email: noha_nasr84@yahoo.com
      • Contact: Noha N. El-Zalabany, Masters; Phone Number: 02 1005365769; Email: noha_nasr84@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Both genders with age range from 20 to 70 years.
• Patients able to return for the follow up visits and can perform oral hygiene measures.
• Clinically diagnosed and histologically confirmed as having oral potentially malignant lesions.
• Patients agreed to sign a written consent after understanding the nature of the study
• Patients have diagnosed oral premalignant lesion/lesions and not yet turned into malignancy (atrophic lichen planus- leukoplakia-erythroplakia - oral submucous fibrosis)

Exclusion Criteria:

• - Diabetic patients (Diabetes Mellitus Type I & II)
• Patients have cardiovascular, lung, Renal, Liver diseases
• Patients on H2 blocker & proton pump inhibitors therapy as Ranitidine (affects metformin absorption and clearance)
• Those with allergy or sensitivity to Metformin or Retinoids therapy or having any contraindication for their use.
• Systemic and/or local systemic drug therapy within the last 3 months prior to the start of the study
• Patients on steroidal or Non-steroidal anti-inflammatory drugs (NSAIDs) for at least the last 6 months
• Patients on Antibiotics treatment for at least the last 2 months
• Patients on Retinoid, green tea supplements or another natural products therapy
• Patients with already diagnosed malignant lesion/lesions
• Pregnant or Lactating females
• Vulnerable groups as prisoners, mentally disabled, etc…

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Metformin Hcl 500Mg 24Hr Sa Tab; Metformin Hcl 500Mg 24Hr Sa Tab drug is given to the patient	Drug: Metformin Hcl 500Mg 24Hr Sa Tab; Glucophage 500 mg once daily; Other Names: Glucophage
Placebo Comparator: control; starch tablets	Other: starch tablet; starch tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate lesion size in millimeters	Evaluate lesion size in millimeters	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of salivary Micro RNA	measuring salivary markers 31& 210 in saliva and also in tissue biopsy	1 year
Measuring immuno-histochemical marker	Measuring cyclin A2 marker in tissues	1 year

Collaborators and Investigators

• Sponsor: Ain Shams University
• Investigators: Study Chair: Fathia Z. Zahran, PHD, Cairo University

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2018
• Primary Completion (Anticipated): June 15, 2019
• Study Completion (Anticipated): September 15, 2019

Study Registration Dates

• First Submitted: September 20, 2018
• First Submitted That Met QC Criteria: September 24, 2018
• First Posted (Actual): September 26, 2018

Study Record Updates

• Last Update Posted (Actual): September 26, 2018
• Last Update Submitted That Met QC Criteria: September 24, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Stomatognathic Diseases; Mouth Diseases; Mouth Neoplasms; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: cairo university (Other Grant/Funding Number: faculty of pedatric dentistry)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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