Effect of Melatonin on the Clinical Outcomes in Type 2 Diabetic Patients With Peripheral Neuropathy
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Concentration of human nuclear factor erythroid 2-related factor (Nrf2)
研究概览
简要总结
The aim of the current study is to measure the effect of melatonin as adjunct therapy on oxidative stress, inflammatory markers and clinical outcome in type 2 diabetic patients with diabetic peripheral neuropathy.
详细描述
Diabetic neuropathy is a microvascular complication affecting 50% of patients throughout their lifetime. It leads to various complications including foot ulcerations and lower limb amputations, thus impairs the patient's quality of life. Distal symmetrical polyneuropathy is the most common subtype. Symptoms include tingling, burning and electrical pain associated with nocturnal exacerbation. Almost 50% of patients are asymptomatic thus diagnosis must include assessment of signs.
Pathophysiologic mechanism behind hyperglycemia induced nerve damage include the activation of various pathways including polyol and advanced glycation end product (AGE), which produces reactive oxygen species. Molecular studies have revealed the involvement of certain transcriptional regulators such as Nrf2-Keap1 and NfKb inflammatory cascade.
Nuclear erythroid growth factor-2 (Nrf2) functions primarily as a defense mechanism in cellular oxidative stress, producing anti-oxidant enzymes as glutathione reductase (GSH) and superoxide dismutase (SOD). However, in long term hyperglycemia, downregulation of nrf2 takes place, leading to accumulation of reactive oxygen species (ROS), which in turn activates nfkb inflammatory pathway and produces various cytokines such as tumor necrosis factor-alpha (Tnf-alpha), interleukin-1 (IL-1) and interleukin-6 (IL-6). Tumor-necrosis factor is known to be highly associated with nerve damage.
Drugs that target disease pathophysiology are currently unavailable, instead DPN management mainly depends on lifestyle modification through weight loss, blood pressure, blood glucose, lipid profile management along with symptomatic care. Yet these fail to stop disease progression.
Melatonin is known to possess anti-oxidant and anti-inflammatory properties through upregulating nrf2. It's hypothesized that adding it to standard therapy shall activate nrf2, and downregulate nfkb pathway and inflammatory cytokines, improving disease progression and patient's quality of life.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 40 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients aged 40-75 years diagnosed with type 2 DM.
- •Diabetes duration at least 1 year.
- •Patients diagnosed with diabetic peripheral neuropathy.
- •Stable antidiabetic medication for at least 1 month before enrollment and during the trial
排除标准
- •Patients with autoimmune disorders (such as lupus and rheumatoid arthritis), thyroid diseases, peripheral arterial disease and cancer patients.
- •Patients with severe kidney or liver dysfunction.
- •Patients diagnosed with neurodegenerative diseases.
- •Active infection.
- •Use of medications or supplements known to cause or treat peripheral neuropathy.
- •Alcohol consumption or substance abuse.
- •Patients consuming any antioxidant supplements or anti-inflammatory medicines during or 3 months before enrollment.
- •Pregnancy or lactation or expecting to get pregnant during the study.
- •Allergy to melatonin.
研究组 & 干预措施
Group 2: control group
Group 2: No intervention, (n=30) patients will receive only standard therapy for 12 weeks
Group 1: Melatonin group
Group 1: Melatonin group (n=30) Patients will receive 10 mg (2 5mg Capsules) 1 hour before bedtime for 12 weeks, in addition to the standard therapy.
干预措施: Melatonin (Drug)
结局指标
主要结局
Concentration of human nuclear factor erythroid 2-related factor (Nrf2)
时间窗: Change from baseline human Nuclear factor erythroid 2-related factor at 3 months.
Oxidative stress marker
次要结局
- D-39 questionnaire(At baseline and after 3 months.)
- Michigan neuropathy screening instrument questionnaire (MNSI-Q)(At baseline and after 3 months)
- Toronto clinical scoring system (TCSS)(At baseline and after 3 months)
- Concentration of Tumor necrosis factor alpha(Change from baseline Tumor necrosis factor alpha at 3 months)
- Diabetic neuropathy score (DNS)(At baseline and after 3 months)
研究者
manar magdy
Demonstrator at Ain shams university
Ain Shams University