Shteamer Jack W, Harvey R Donald, Spektor Boris, Curseen Kimberly, Egan Katherine, Chen Zhengjia, Gillespie Theresa W, Sniecinski Roman M, Singh Vinita
Department of Anesthesiology, Emory University, Atlanta, GA, United States.
Department of Pharmacology, Emory University, Atlanta, GA, United States.
JMIR Res Protoc. 2019 Apr 30;8(4):e12125. doi: 10.2196/12125.
Approximately 12 million Americans are affected with cancer. Of these, 53% experience pain at all stages of cancer. Pain may remain uncontrolled despite high-dose opioid therapy, and opioids have many well-documented harmful side effects. Intranasal ketamine has been shown to be effective in controlling breakthrough noncancer pain in a double-blind randomized control trial (DBRCT) by Carr et al in 2003 as well as to help with depression in a DBRCT by Lapidus et al in 2014. We seek to obtain preliminary data on the safety, feasibility, and utility of this novel technique for the treatment of uncontrolled cancer pain.
This study aimed to obtain preliminary data via a clinical trial addressing the safety, feasibility, pharmacokinetics, and pharmacodynamics of intranasal ketamine. These initial findings will be applied to a subsequent trial to determine the effectiveness and associated toxicities of ketamine in a larger sample of cancer patients and to address the compelling need to identify new, successful management therapies for cancer pain.
This is an institutional review board- and investigational new drug-approved, prospective phase I/II trial to investigate the safety and use of intranasal ketamine in patients with uncontrolled pain related to cancer or cancer treatment. Informed consent will be obtained prior to all study procedures. All patients will be assigned to the same investigational treatment arm. After patient selection via inclusion/exclusion criteria, patients will be seen over 5 visits, with each visit conducted 2-7 days apart. Patients will be administered ketamine on visits 1-4 and monitored for 240 minutes with continuous pulse oximetry and regular blood pressure checks. Blood samples as well as patient-reported outcomes will be collected at set time points at baseline and after drug delivery. Patients will receive 10 mg intranasal ketamine on visit 1, 10 mg intravenous ketamine on visit 2, 30 mg intranasal ketamine on visit 3, and 50 mg intranasal ketamine on visit 4. On visit 5, an addition blood sample will be drawn.
As of March 2019, enrollment is in progress, and a total of 7 subjects have completed the study. Enrollment is expected to be completed by April 2019. Final data analysis will commence soon after, and the results are expected to be submitted for publication in 2019.
If intranasal ketamine can be utilized for pain control in cancer patients, it could provide superior analgesia and better quality of life, without the risk of significant respiratory depression and constipation associated with opioid medications. These findings will be an important initial step toward testing the effectiveness of intranasal ketamine as a nonopioid medication for cancer pain and as potential maintenance outpatient therapy.
ClinicalTrials.gov NCT03146806; https://clinicaltrials.gov/ct2/show/NCT03146806.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/12125.
约1200万美国人受癌症影响。其中，53%在癌症各阶段经历疼痛。尽管采用高剂量阿片类药物治疗，疼痛仍可能无法得到控制，且阿片类药物有许多已充分记录的有害副作用。2003年卡尔等人进行的一项双盲随机对照试验（DBRCT）表明，鼻内氯胺酮在控制突破性非癌性疼痛方面有效，2014年拉皮德斯等人进行的一项DBRCT显示其有助于缓解抑郁症。我们试图获取关于这种新技术治疗无法控制的癌痛的安全性、可行性和效用的初步数据。
本研究旨在通过一项临床试验获取关于鼻内氯胺酮的安全性、可行性、药代动力学和药效学的初步数据。这些初步发现将应用于后续试验，以确定氯胺酮在更大样本的癌症患者中的有效性和相关毒性，并满足确定新的、成功的癌痛管理疗法的迫切需求。
这是一项经机构审查委员会和研究性新药批准的前瞻性I/II期试验，旨在研究鼻内氯胺酮在与癌症或癌症治疗相关的无法控制的疼痛患者中的安全性和应用。在所有研究程序之前将获得知情同意。所有患者将被分配到相同的研究治疗组。通过纳入/排除标准选择患者后，患者将接受5次就诊，每次就诊间隔2 - 7天。患者将在第1 - 4次就诊时接受氯胺酮治疗，并通过连续脉搏血氧饱和度监测和定期血压检查进行240分钟的监测。在基线和给药后设定的时间点收集血样以及患者报告的结果。患者在第1次就诊时接受10毫克鼻内氯胺酮，第2次就诊时接受10毫克静脉注射氯胺酮，第3次就诊时接受30毫克鼻内氯胺酮，第4次就诊时接受50毫克鼻内氯胺酮。在第5次就诊时，将抽取额外的血样。
截至2019年3月，入组正在进行中，共有7名受试者完成了研究。预计入组将于2019年4月完成。最终数据分析将在之后不久开始，结果预计于2019年提交发表。
如果鼻内氯胺酮可用于控制癌症患者的疼痛，它可以提供更好的镇痛效果和更高的生活质量，而没有与阿片类药物相关的显著呼吸抑制和便秘风险。这些发现将是测试鼻内氯胺酮作为癌痛非阿片类药物和潜在维持门诊治疗有效性的重要第一步。
ClinicalTrials.gov NCT03146806；https://clinicaltrials.gov/ct2/show/NCT03146806。
国际注册报告识别码（IRRID）：DERR1 - 10.2196/12125。
