Cargando…
Safety of Intranasal Ketamine for Reducing Uncontrolled Cancer-Related Pain: Protocol of a Phase I/II Clinical Trial
BACKGROUND: 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 effectiv...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
JMIR Publications
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658277/ https://www.ncbi.nlm.nih.gov/pubmed/31038469 http://dx.doi.org/10.2196/12125 |
_version_ | 1783438936945721344 |
---|---|
author | Shteamer, Jack W Harvey, R Donald Spektor, Boris Curseen, Kimberly Egan, Katherine Chen, Zhengjia Gillespie, Theresa W Sniecinski, Roman M Singh, Vinita |
author_facet | Shteamer, Jack W Harvey, R Donald Spektor, Boris Curseen, Kimberly Egan, Katherine Chen, Zhengjia Gillespie, Theresa W Sniecinski, Roman M Singh, Vinita |
author_sort | Shteamer, Jack W |
collection | PubMed |
description | BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT03146806; https://clinicaltrials.gov/ct2/show/NCT03146806. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/12125 |
format | Online Article Text |
id | pubmed-6658277 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | JMIR Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-66582772019-08-08 Safety of Intranasal Ketamine for Reducing Uncontrolled Cancer-Related Pain: Protocol of a Phase I/II Clinical Trial Shteamer, Jack W Harvey, R Donald Spektor, Boris Curseen, Kimberly Egan, Katherine Chen, Zhengjia Gillespie, Theresa W Sniecinski, Roman M Singh, Vinita JMIR Res Protoc Protocol BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT03146806; https://clinicaltrials.gov/ct2/show/NCT03146806. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/12125 JMIR Publications 2019-04-30 /pmc/articles/PMC6658277/ /pubmed/31038469 http://dx.doi.org/10.2196/12125 Text en ©Jack W Shteamer, R Donald Harvey, Boris Spektor, Kimberly Curseen, Katherine Egan, Zhengjia Chen, Theresa W Gillespie, Roman M Sniecinski, Vinita Singh. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 30.04.2019. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Research Protocols, is properly cited. The complete bibliographic information, a link to the original publication on http://www.researchprotocols.org, as well as this copyright and license information must be included. |
spellingShingle | Protocol Shteamer, Jack W Harvey, R Donald Spektor, Boris Curseen, Kimberly Egan, Katherine Chen, Zhengjia Gillespie, Theresa W Sniecinski, Roman M Singh, Vinita Safety of Intranasal Ketamine for Reducing Uncontrolled Cancer-Related Pain: Protocol of a Phase I/II Clinical Trial |
title | Safety of Intranasal Ketamine for Reducing Uncontrolled Cancer-Related Pain: Protocol of a Phase I/II Clinical Trial |
title_full | Safety of Intranasal Ketamine for Reducing Uncontrolled Cancer-Related Pain: Protocol of a Phase I/II Clinical Trial |
title_fullStr | Safety of Intranasal Ketamine for Reducing Uncontrolled Cancer-Related Pain: Protocol of a Phase I/II Clinical Trial |
title_full_unstemmed | Safety of Intranasal Ketamine for Reducing Uncontrolled Cancer-Related Pain: Protocol of a Phase I/II Clinical Trial |
title_short | Safety of Intranasal Ketamine for Reducing Uncontrolled Cancer-Related Pain: Protocol of a Phase I/II Clinical Trial |
title_sort | safety of intranasal ketamine for reducing uncontrolled cancer-related pain: protocol of a phase i/ii clinical trial |
topic | Protocol |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658277/ https://www.ncbi.nlm.nih.gov/pubmed/31038469 http://dx.doi.org/10.2196/12125 |
work_keys_str_mv | AT shteamerjackw safetyofintranasalketamineforreducinguncontrolledcancerrelatedpainprotocolofaphaseiiiclinicaltrial AT harveyrdonald safetyofintranasalketamineforreducinguncontrolledcancerrelatedpainprotocolofaphaseiiiclinicaltrial AT spektorboris safetyofintranasalketamineforreducinguncontrolledcancerrelatedpainprotocolofaphaseiiiclinicaltrial AT curseenkimberly safetyofintranasalketamineforreducinguncontrolledcancerrelatedpainprotocolofaphaseiiiclinicaltrial AT egankatherine safetyofintranasalketamineforreducinguncontrolledcancerrelatedpainprotocolofaphaseiiiclinicaltrial AT chenzhengjia safetyofintranasalketamineforreducinguncontrolledcancerrelatedpainprotocolofaphaseiiiclinicaltrial AT gillespietheresaw safetyofintranasalketamineforreducinguncontrolledcancerrelatedpainprotocolofaphaseiiiclinicaltrial AT sniecinskiromanm safetyofintranasalketamineforreducinguncontrolledcancerrelatedpainprotocolofaphaseiiiclinicaltrial AT singhvinita safetyofintranasalketamineforreducinguncontrolledcancerrelatedpainprotocolofaphaseiiiclinicaltrial |