"The Effect of Memantine on the Prevention and Amelioration of Paclitaxel-induced Toxicity in Breast Cancer Patients"
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Incidence and grading of paclitaxel induced peripheral neuropathy (PIPN)
研究概览
简要总结
Cancer is currently a leading cause of morbidity and mortality worldwide. Chemotherapeutic agents, despite being effective in arresting the progression of cancer by targeting and eliminating rapidly dividing cancer cells, are associated with various adverse effects. Chemotherapy-induced peripheral neuropathy (CIPN) is a serious clinical adverse effect of certain chemotherapeutic agents. For many patients, CIPN symptoms could be severe, disabling, and significantly impairing the activities of daily living (ADL) and diminishing the quality of life (QoL). Paclitaxel-induced peripheral neuropathy may affect up to 97% of paclitaxel-treated patients and become chronic in more than 60% of cases. The initial symptoms of paclitaxel-induced peripheral neuropathy (PIPN) include numbness, tingling, and allodynia (painful sensations in response to normally non-painful stimuli) that can be manifested in the patient's fingers and toes within 24-72 h post-injection. These symptoms may later progress to affect the patient's lower leg and wrists in a "glove and stocking" pattern. Symptoms typically begin distally and continue proximally as the situation worsens. Memantine is a non-competitive NMDA receptor antagonist that inhibits the prolonged influx of Ca2+, responsible for neuronal excitotoxicity while maintaining the physiological NMDA receptor's function and avoiding psychotropic adverse events. Although memantine has been the main treatment option for moderate and severe Alzheimer's disease in the last two decades, numerous studies have investigated its other potential uses. Some studies showed that memantine diminished chronic pain in complex regional pain syndrome, phantom limb pain, and fibromyalgia. Most in vivo and in vitro studies attributed the neuroprotective effects of memantine to the blockade of NMDA receptors on neurons as well as inhibition of microglia activation with subsequent reduction of pro-inflammatory mediators' production such as extracellular superoxide anion, intracellular ROS, nitric oxide, prostaglandin E2, and TNF-α, and stimulation of neurotrophic factor release from astroglia.
详细描述
Up till now, no treatment options are available for prevention of PIPN. Several options have been investigated for treatment of CIPN with only duloxetine had proven benefits. Additional investigations are needed to develop preventive and ameliorative therapy of PIPN.
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
- Triple (Participant, Care Provider, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Adult patients (>18 years old).
- •Patients with confirmed diagnosis of non-metastatic breast cancer planned to receive weekly adjuvant/neo-adjuvant paclitaxel.
- •Patients with Eastern Cooperative Oncology Group (ECOG) performance (Oken et al., 1982) status of 0-2.
排除标准
- •Patients with pre-existing neuropathic conditions.
- •Patients with diabetes mellitus.
- •Patients with a history of seizure disorder.
- •Patients with renal impairment (creatinine clearance less than 60 ml/min), or hepatic impairment (defined as ALT an AST > 3 times upper limits of normal)
- •Patients with inadequate bone marrow functions (defined as absolute neutrophilic count less than 1,500/mm3 or platelets count less than 100,000/mm3).
- •Concomitant use of vitamin B1, B6, B9, or B
- •Patients receiving medications that possibly induce peripheral neuropathy including amiodarone, colchicine, metronidazole, antimycobacterials, and nucleoside reverse transcriptase inhibitors, and phenytoin (Jones et al., 2020).
- •Patients receiving gabapentinoids, antidepressants, or opioids.
- •Pregnancy or lactation.
- •History of hypersensitivity to memantine.
研究组 & 干预措施
Control arm
Forty patients who will receive placebo once daily in addition to weekly 80 mg/m2 of paclitaxel for 12 weeks.
干预措施: Placebo Oral Tablet (Drug)
Treatment arm
Forty patients who will receive memantine 20 mg once daily in addition to weekly 80 mg/m2 of paclitaxel for 12 weeks.
干预措施: Memantine-HCl (Drug)
结局指标
主要结局
Incidence and grading of paclitaxel induced peripheral neuropathy (PIPN)
时间窗: Weekly for 12 weeks.
Patients will be subjected to neurological examination every cycle to identify the presence and severity of PIPN. Grading of PIPN will be determined using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5 published in November 2017 (NCI, 2017). The NCI-CTCAE grades the adverse events based on their severity on a 5-point scale where "Grade 1" is defined as: Mild or asymptomatic symptoms requiring clinical or diagnostic observations only; Intervention not indicated. "Grade 2": Moderate symptoms limiting age-appropriate ADL; minimal, local or noninvasive intervention is indicated. "Grade 3": Severe symptoms or medically significant but not life-threatening that are disabling or limiting self-care in ADL; hospitalization or prolongation of hospitalization is indicated. "Grade 4": Life threatening consequences; urgent or emergent intervention is needed. "Grade 5": Death related to adverse event. The primary outcome will be the difference i
次要结局
- Serum levels of nerve growth factor (NGF)(Baseline and at 12 weeks.)
- Pain severity(Weekly for 12 weeks.)
- Patients' QoL(baseline, at 6 weeks, and 12 weeks.)
- Severity of depressive symptoms(Baseline, at 6 weeks, and 12 weeks.)
研究者
Mahmoud Mustafa Mahmoud Gharib
Assistant lecturer at Pharmacy Practice & Clinical Pharmacy Department, Future University in Egypt
Ain Shams University