The effect of a topical combination of clonidine and pentoxifylline on post-traumatic neuropathic pain patients: study protocol for a randomized, double-blind placebo-controlled trial
Abstract Background First-line pharmacotherapy for neuropathic pain entails the use of systemic antidepressants and anticonvulsants. These drugs are not optimally effective and poorly tolerated, especially for older patients with comorbid conditions. Given the high number of such patients, there is...
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| Format: | Article |
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BMC
2021-02-01
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| Series: | Trials |
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| Online Access: | https://doi.org/10.1186/s13063-021-05088-w |
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| author | Oli Abate Fulas André Laferrière D. Mark A. Ware Yoram Shir Terence J. Coderre |
| author_facet | Oli Abate Fulas André Laferrière D. Mark A. Ware Yoram Shir Terence J. Coderre |
| author_sort | Oli Abate Fulas |
| collection | DOAJ |
| description | Abstract Background First-line pharmacotherapy for neuropathic pain entails the use of systemic antidepressants and anticonvulsants. These drugs are not optimally effective and poorly tolerated, especially for older patients with comorbid conditions. Given the high number of such patients, there is a need for a greater repertoire of safer and more effective analgesics. Clonidine and pentoxifylline are vasodilator agents that work synergistically to enhance tissue perfusion and oxygenation. The topical administration of these drugs, individually and in combination, has shown anti-nociceptive properties in rodent models of neuropathic pain. A topically-administered combination of clonidine and pentoxifylline also effectively reduced the intensity of both spontaneous and evoked pain in healthy volunteers with experimentally-induced neuropathic pain. The next step in advancing this formulation to clinical use is the undertaking of a phase II clinical study to assess its efficacy and safety in neuropathic pain patients. Methods/design This is a study protocol for a randomized, double-blind, placebo-controlled, phase II clinical trial with a cross-over design. It is a single-centered, 5-week study that will enroll a total of 32 patients with post-traumatic peripheral neuropathic pain. Patients will be treated topically with either a combination of clonidine and pentoxifylline or placebo for a period of 2 weeks each, in randomly assigned order across patients, with an intervening washout period of 1 week. The primary outcome measures of the study are the intensity of spontaneous pain recorded daily in a pain diary with a visual analog scale, and the degree of mechanical allodynia evoked by a brush stimulus. The secondary outcome measures of the study include scores of pain relief and change in the area of punctate hyperalgesia. This trial has been prospectively registered with ClinicalTrials.gov on November 1, 2017. ClinicalTrials.gov Identifier: NCT03342950 . Discussion The analgesic use of topical treatment with clonidine and pentoxifylline in combination has not been investigated in post-traumatic neuropathic pain. This study could generate the first evidence for the efficacy and safety of the formulation in alleviating pain in patients with neuropathic pain. Furthermore, this trial will provide objective grounds for the investigation of other agents that enhance tissue oxygenation in the topical treatment of peripheral neuropathic pain. Trial registration This trial has been registered with ClinicalTrials.gov owned by NIH’s US National Library of Medicine. ClinicalTrials.gov NCT03342950 . Registered on November 1, 2017 (trial was prospectively registered). Protocol version and identifiers This is protocol version 5, dated June 2018. McGill University Health Center (MUHC) Reaseach Ethics Board (REB) identification number: TTNP 2018-3906. |
| first_indexed | 2024-12-24T01:36:52Z |
| format | Article |
| id | doaj.art-06f3df1d93094f7abe4f13fb44ffb47b |
| institution | Directory Open Access Journal |
| issn | 1745-6215 |
| language | English |
| last_indexed | 2024-12-24T01:36:52Z |
| publishDate | 2021-02-01 |
| publisher | BMC |
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| series | Trials |
| spelling | doaj.art-06f3df1d93094f7abe4f13fb44ffb47b2022-12-21T17:22:10ZengBMCTrials1745-62152021-02-0122111010.1186/s13063-021-05088-wThe effect of a topical combination of clonidine and pentoxifylline on post-traumatic neuropathic pain patients: study protocol for a randomized, double-blind placebo-controlled trialOli Abate Fulas0André Laferrière1D. Mark A. Ware2Yoram Shir3Terence J. Coderre4Department of Anesthesia, McGill UniversityDepartment of Anesthesia, McGill UniversityAlan Edwards Pain Management Unit, McGill University Health CentreAlan Edwards Pain Management Unit, McGill University Health CentreDepartment of Anesthesia, McGill UniversityAbstract Background First-line pharmacotherapy for neuropathic pain entails the use of systemic antidepressants and anticonvulsants. These drugs are not optimally effective and poorly tolerated, especially for older patients with comorbid conditions. Given the high number of such patients, there is a need for a greater repertoire of safer and more effective analgesics. Clonidine and pentoxifylline are vasodilator agents that work synergistically to enhance tissue perfusion and oxygenation. The topical administration of these drugs, individually and in combination, has shown anti-nociceptive properties in rodent models of neuropathic pain. A topically-administered combination of clonidine and pentoxifylline also effectively reduced the intensity of both spontaneous and evoked pain in healthy volunteers with experimentally-induced neuropathic pain. The next step in advancing this formulation to clinical use is the undertaking of a phase II clinical study to assess its efficacy and safety in neuropathic pain patients. Methods/design This is a study protocol for a randomized, double-blind, placebo-controlled, phase II clinical trial with a cross-over design. It is a single-centered, 5-week study that will enroll a total of 32 patients with post-traumatic peripheral neuropathic pain. Patients will be treated topically with either a combination of clonidine and pentoxifylline or placebo for a period of 2 weeks each, in randomly assigned order across patients, with an intervening washout period of 1 week. The primary outcome measures of the study are the intensity of spontaneous pain recorded daily in a pain diary with a visual analog scale, and the degree of mechanical allodynia evoked by a brush stimulus. The secondary outcome measures of the study include scores of pain relief and change in the area of punctate hyperalgesia. This trial has been prospectively registered with ClinicalTrials.gov on November 1, 2017. ClinicalTrials.gov Identifier: NCT03342950 . Discussion The analgesic use of topical treatment with clonidine and pentoxifylline in combination has not been investigated in post-traumatic neuropathic pain. This study could generate the first evidence for the efficacy and safety of the formulation in alleviating pain in patients with neuropathic pain. Furthermore, this trial will provide objective grounds for the investigation of other agents that enhance tissue oxygenation in the topical treatment of peripheral neuropathic pain. Trial registration This trial has been registered with ClinicalTrials.gov owned by NIH’s US National Library of Medicine. ClinicalTrials.gov NCT03342950 . Registered on November 1, 2017 (trial was prospectively registered). Protocol version and identifiers This is protocol version 5, dated June 2018. McGill University Health Center (MUHC) Reaseach Ethics Board (REB) identification number: TTNP 2018-3906.https://doi.org/10.1186/s13063-021-05088-wTopical treatmentPost-traumatic peripheral neuropathic painPentoxifyllineClonidineDynamic mechanical allodyniaPunctate hyperalgesia |
| spellingShingle | Oli Abate Fulas André Laferrière D. Mark A. Ware Yoram Shir Terence J. Coderre The effect of a topical combination of clonidine and pentoxifylline on post-traumatic neuropathic pain patients: study protocol for a randomized, double-blind placebo-controlled trial Trials Topical treatment Post-traumatic peripheral neuropathic pain Pentoxifylline Clonidine Dynamic mechanical allodynia Punctate hyperalgesia |
| title | The effect of a topical combination of clonidine and pentoxifylline on post-traumatic neuropathic pain patients: study protocol for a randomized, double-blind placebo-controlled trial |
| title_full | The effect of a topical combination of clonidine and pentoxifylline on post-traumatic neuropathic pain patients: study protocol for a randomized, double-blind placebo-controlled trial |
| title_fullStr | The effect of a topical combination of clonidine and pentoxifylline on post-traumatic neuropathic pain patients: study protocol for a randomized, double-blind placebo-controlled trial |
| title_full_unstemmed | The effect of a topical combination of clonidine and pentoxifylline on post-traumatic neuropathic pain patients: study protocol for a randomized, double-blind placebo-controlled trial |
| title_short | The effect of a topical combination of clonidine and pentoxifylline on post-traumatic neuropathic pain patients: study protocol for a randomized, double-blind placebo-controlled trial |
| title_sort | effect of a topical combination of clonidine and pentoxifylline on post traumatic neuropathic pain patients study protocol for a randomized double blind placebo controlled trial |
| topic | Topical treatment Post-traumatic peripheral neuropathic pain Pentoxifylline Clonidine Dynamic mechanical allodynia Punctate hyperalgesia |
| url | https://doi.org/10.1186/s13063-021-05088-w |
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