A Pilot Randomized, Placebo Controlled, Double Blind Study of Omega-3 Fatty Acids to Prevent Paclitaxel Associated Acute Pain Syndrome
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Mean severity of pain
研究概览
简要总结
Paclitaxel, a widely used chemotherapeutic agent, is associated with several well-known side effects including neuropathy (weakness, numbness and pain) and generalized body aches. The latter has recently been described as paclitaxel-associated acute pain syndrome (P-APS) and often occurs in the first three to four days after administration. It affects about 58-90% of patients. Currently, the mechanism of P-APS is unknown, and there is no standard of care to treat it. However, an intervention with both anti-inflammatory as well as neuroprotective properties would be an ideal candidate for testing in the prevention of P-APS and subsequent development of peripheral neuropathy. Previous studies have suggested that omega-3 fatty acids may act as neuroprotective agents, and there are no currently documented safety concerns with their combined use with paclitaxel.
Therefore, this randomized pilot clinical trial will determine whether omega-3 fatty acids can treat pain in patients with breast or ovarian cancer receiving paclitaxel.
详细描述
One mechanism proposed for P-APS is an early inflammatory process characterized by macrophage activation in both the dorsal root ganglia and peripheral nerve occurring shortly after paclitaxel therapy. Morphologic alterations in DRG satellite cells have been noted and upregulation of proinflammatory cytokines have been hypothesized as early events in the development of neuropathy. Therefore, it is possible that paclitaxel-induced neuropathic pain may be mediated by pro-inflammatory cytokines. If P-APS and chronic neuropathy are indeed part of a continuum, the inflammatory pathway would be a reasonable target for therapy. While the mechanism of how paclitaxel leads to the development of neuropathy is still not understood, it has been hypothesized that its microtubule-stabilizing effects disrupt axonal transport. Intervention with an agent that is both anti-inflammatory as well as neuroprotective is therefore worth exploring.
Long chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are common dietary supplements. They have well established anti-inflammatory properties which serve as the basis for their use in therapeutic trials in inflammatory conditions. Omega -3 fatty acids consumption can attenuate the production of pro-inflammatory metabolites. In addition, it can generate local mediators that facilitate resolution of inflammation. Thus, if P-APS is indeed mediated by inflammation, the anti-inflammatory activity of omega 3 fatty acids may be one mechanism to prevent P-APS. Additionally, given its well established safety profile, it may be an attractive alternative to NSAIDS.
A dose of at least 2.7 g/day of EPA and DHA have been reported to have analgesic effects in inflammatory conditions. The dose of 4 g/day is an FDA-approved dose of omega 3 fatty acids (Lovaza) for the treatment of hypertriglyceridemia and has a well-documented toxicity profile. On the basis of this, a dose of 4 g/day was selected for this study. Lovaza (omega-3-acid ethyl esters) capsules will be used. Each 1-gram capsule contains approximately 465 mg EPA and 375 mg DHA.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients have a diagnosis of breast cancer or ovarian cancer
- •Patients are scheduled to receive weekly paclitaxel at 70-90 mg/m^2 for a minimum of 2 months; 3 out of 4 weeks is allowed
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1 or 2
- •Patients must not have taken omega-3-fatty acid supplements within the past 1 month prior to registration and must agree to refrain from use of omega- 3 fatty acid supplements from sources outside the study
- •Patients must not be on nonsteroidal anti-inflammatory drugs (NSAIDS) or aspirin for at least 1 week prior to registration; NSAIDS or aspirin are allowed after enrollment
- •Patients must not have received any other analgesics (opiates and tramadol) 1 week prior to registration; analgesics (opiates and tramadol) are allowed after enrollment
- •Patients must have the ability to complete questionnaires by themselves or with assistance
- •Patients must not be on anticoagulation medication (heparin/ warfarin) within 28 days prior to registration, because of increased risk of bleeding
- •Concurrent treatment with carboplatin +/- bevacizumab is allowed
- •Concurrent treatment with human epidermal growth factor receptor (Her2 neu) targeted therapy is allowed
排除标准
- •Known allergy to omega 3 fatty acids, fish or shellfish
- •Pre-existing diagnosis of peripheral neuropathy
- •Diagnosis of fibromyalgia
- •Concurrent planned neutrophil colony stimulating factor therapy
- •Prior exposure to paclitaxel within the last 6 months
研究组 & 干预措施
Arm I (Omega-3 fatty acid)
Four Omega-3 fatty acid capsules (at 1 gram/capsule) are administered orally daily.
The capsules may be administered either once daily or as 2 capsules two times daily.
干预措施: Omega-3 fatty acid (Dietary Supplement)
Arm I (Omega-3 fatty acid)
Four Omega-3 fatty acid capsules (at 1 gram/capsule) are administered orally daily.
The capsules may be administered either once daily or as 2 capsules two times daily.
干预措施: Paclitaxel (Drug)
Arm II (placebo)
Four placebo capsules (at 1 gram microcrystalline cellulose/capsule) are administered orally daily.
The capsules may be administered either once daily or as 2 capsules two times daily.
干预措施: Placebo (Dietary Supplement)
Arm II (placebo)
Four placebo capsules (at 1 gram microcrystalline cellulose/capsule) are administered orally daily.
The capsules may be administered either once daily or as 2 capsules two times daily.
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Mean severity of pain
时间窗: Up to 1 month after completion of therapy
Differences between groups will analyzed via t-tests or Wilcoxon rank-sum tests as appropriate.
次要结局
- Incidence of pain or relief(Up to 1 month after completion of therapy)