Cancer Chemoprevention by Metformin Hydrochloride Compared to Placebo in Oral Potentially Malignant Lesions: A Randomized Clinical Trial (Part 1)
试验速览
- 阶段
- 3 期
- 入组人数
- 62
- 试验地点
- 1
- 主要终点
- Clinical Outcomes
研究概览
简要总结
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 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.
Metformin, one of most widely prescribed oral hypoglycemic agents, has recently received increased attention because of its potential anti-tumorigenic effects that are thought to be independent of its hypoglycemic effects. Evans et al. first found an association between metformin use and decreased cancer incidence.
The study will reveal whether Systemic Metformin hydrochloride treatment given to patients with oral potentially malignant lesions improve the prognosis and prevent or at least reduce the incidence of malignant transformation?
详细描述
The idea of identifying oral lesions with a precancerous nature, that is, in the sense of pertaining to a pathologic process with an increased risk for future malignant development, of course, is to prevent frank malignancy to occur in the affected area.
In 2005, WHO categorized any lesion or condition that may increase the risk of malignant transformation as an 'oral potentially malignant disorder' (OPMD). Early detection of cancer development from oral premalignant lesions (OPLs) plays an important role in successful therapy. The management of OPMDs varies according to the type of lesion and often differs between treatment centers. However, it remains unclear if excision of leukoplakia/erythroplakia protects patients against the development of OSCC and no randomized controlled trials have been performed to address this issue.
Various treatment modalities, such as systemic therapies and surgical removal, have been suggested. The systemic therapies tested so far include retinoids, extracts of green tea, inhibitors of cyclooxygenase-2 and of epidermal growth factor, and peroxisome proliferator-activated receptor-c agonists, but there is no generally approved standard systemic therapy regimen so far.
Local removal includes photodynamic therapy, laser therapy, cryotherapy and conventional removal by scalpel, but no treatment has so far gained universal approval, no treatment has so far been subjected to a randomized clinical trial (RCT), and no treatment has been shown to prevent recurrence or significantly reduce malignant development in long-term follow-up studies. It is well established that no treatment results in malignant development at an annual rate of 2-3%.
The overall purpose of treatment therefore is to reduce this percentage. However, the situation is to take responsibility for the welfare of the patients still is, as it has been so far: despite treatment, in some types of lesions cancers do occur, so the important question is whether the harm to patients by not treating or by treating them? Lack of randomized clinical trials accounts for this persistent question, and while waiting for such studies to be reported, it is necessary to reflect on the existing scenarios.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 20 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 (Atrophic oral lichen planus, leukoplakia, erythroplakia and oral submucous fibrosis).
- •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
排除标准
- •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 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...
研究组 & 干预措施
Metformin-Group
Metformin hydrochloride tablets 500 mg taken orally once daily for 3 months
干预措施: Metformin Hydrochloride 500 MG (Drug)
Placebo-Group
Starch placebo tablets taken orally once daily for 3 months
干预措施: Placebo Oral Tablet (Drug)
结局指标
主要结局
Clinical Outcomes
时间窗: 3 months
Effect of Systemic Metformin hydrochloride on the millimeters change in the largest diameter of the oral potentially malignant lesion
次要结局
- Immunohistochemical analysis(3 months)
- microRNA analysis(3 months)
- Salivary microRNA(3 months)
研究者
Ahmed Adel Mohamed Abdelazim
Assistant Lecturer
Cairo University