Neuralgia PeripheralPhase 2TTNPNCT03342950
The Effects of Topical Treatment With Clonidine + Pentoxifylline in Patients With Neuropathic Pain
A Phase 2 study testing Topical Solution in people with Neuralgia Peripheral, run by Terence J. Coderre at 1 site in Canada.
Trial summary
Microvascular dysfunction underlies pain in different animal models of neuropathic pain. Pentoxifylline is a phosphodiesterase inhibitor that reduces cyclic adenosine monophosphate (cAMP) hydrolysis, enhances blood flow and reduces platelet aggregation, decreases blood viscosity, and increases the flexibility of red… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Neuralgia Peripheral
- What is being tested?
- Topical Solution
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 4 participants
- Where
- 1 siteCanada
- Study dates
- 19 Feb 2019to 12 Oct 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female or male patients, aged 18-70;
- An average spontaneous pain level of at least 4 on an 11-point numerical rating pain score (0= no pain, 10= worst pain possible) on at least 3 days during the week prior to the study;
- The existence of tactile allodynia, as a sign of chronic pain, following a traumatic peripheral nerve injury;
- Ability to communicate in English or in French;
- Willing and able to sign an informed consent;
- Stable pain disease with no anticipated change in treatment in the next 5 weeks.
- Female subjects of childbearing potential must agree to use effective method of contraception during the study period. Female subjects who utilize a hormonal contraceptive as one of their birth control methods must have consistently used the same method for at least three months prior to study drug dosing.
Who cannot join
- Diabetes mellitus necessitating antihyperglycemic treatment or any other endocrine disease;
- Any liver disease, resulting in aspartate aminotransferase (AST) levels greater than 3 times the normal values, or kidney disease, resulting in creatinine levels greater than 133 µmol/L;
- Hypertension or taking of anti-hypertensive medication;
- Malignant disease or taking of chemotherapeutic agents;
- Known diagnosis of angina pectoris, arrhythmias, congestive heart failure or peripheral arterial disease;
- Pregnancy or breast feeding. Female patients of child-bearing age must have a negative urine pregnancy test;
Show all 11Show fewer
- Known allergic reaction to clonidine or pentoxifylline;
- Presence of major depression, bipolar affective disorder or schizophrenia;
- Presence of a severe medical condition, or condition known to affect peripheral circulation (intermittent claudication, peripheral arterial disease, Raynaud's syndrome);
- any medication that interacts with clonidine or pentoxifylline [e.g. cardiovascular drugs such as angiotensin converting enzyme (ACE) inhibitors, alpha blockers (prazosin, terazosin or doxazosin), beta blockers (atenolol, metoprolol, propranolol), neuroleptics (butyrophenones, phenothiazines, thioxanthenes), calcium channel blockers (verapamil, diltiazem) and non-cardiovascular drugs such as diuretics, thyroxine, monoamine oxidase inhibitors and selective serotonin reuptake inhibitors (SSRIs), as well as vitamin K antagonists/blood thinners, such as warfarin];
- any medical condition that might be impacted by clonidine or pentoxifylline, such as cardiovascular disease, cardiac rhythm disorders (atrial-ventricular blockade or conduction abnormalities), orthostatic regulation disturbances, disorders of cerebral perfusion, chronic renal failure; sinus node dysfunction, or a recent cerebral and/or retinal haemorrhage.
Trial locations and contacts
1 site in 1 country.
About this study
Microvascular dysfunction underlies pain in different animal models of neuropathic pain. Pentoxifylline is a phosphodiesterase inhibitor that reduces cyclic adenosine monophosphate (cAMP) hydrolysis, enhances blood flow and reduces platelet aggregation, decreases blood viscosity, and increases the flexibility of red blood cells, all of which relieve microvascular dysfunction. Clonidine is an α2-adrenergic receptor agonist that decreases sympathetic outflow from the brainstem, vascular reactivity and has direct peripheral vasodilatory action. Topical combination of pentoxifylline and clonidine produced significant antiallodynic effects in rat models of neuropathic pain with sciatic nerve injury, painful diabetic neuropathy, and chemotherapy-induced painful neuropathy. In healthy volunteers with an experimentally-induced surrogate for neuropathic pain: post-capsaicin tourniquet exposure, the topical combination reduced areas of dynamic allodynia and mechanical hyperalgesia, in addition to reducing post-capsaicin ischemic pain.
This study will investigate if the same topical combination of clonidine + pentoxifylline will relieve pain in patients with neuropathic pain following traumatic injuries of peripheral nerves.
- Conditions
- Neuralgia Peripheral
- Being tested
- Topical Solution, Placebos
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Topical SolutionDrug
Topical Solution of Clonidine (0.01%) + Pentoxifylline (5%) in anhydrous ethanol (6.5%), polyethylene glycol 400 (20%), propylene glycol (53.5%), and oleyl alcohol (20%)
PlacebosDrug
Topical Solution of anhydrous ethanol (6.5%), polyethylene glycol 400 (20%), propylene glycol (53.5%), and oleyl alcohol (20%)
| Study group | Role | What they receive |
|---|---|---|
| Active drug group | Active comparator | Treatment with the topical solution of clonidine + pentoxifylline (0.1%/5%) Receives: Drug: Topical Solution |
| Placebo group | Placebo comparator | Treatment with placebo solution with out active drug ingredients Receives: Drug: Placebos |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in visual analogue scale (VAS) score of spontaneous pain intensity
This will be an evaluation of patients' daily spontaneous pain recorded on a pain diary. The visual analogue scale is a 100 millimetre line with the words "no pain" and "worst pain possible" on the left and right of it respectively. The patients will indicate their level of pain by marking on the line. The position of the mark on the line from the left end to the right will be measured in millimetres to obtain level of pain severity (The higher the VAS score the more severe the pain) . Change in VAS score will be obtained by comparing the difference between scores recorded on trial day 1 versus trial day 14 and trial day 21 versus trial day 35.
Measured: Scores recorded on pain diary on trial day 1, day 14 , day 21 and day 35 will be used
Change in visual analogue scale (VAS) score of dynamic mechanical allodynia (DMA)
The degree of dynamic mechanical allodynia will be determined by stroking the most painfully sensitive area of the skin three times over 5 seconds at a rate of 1-2 cm/s with a Somedic brush. The patient will indicate the amount of pain evoked on a 100-millimeter visual analogue scale (VAS) by marking on a 100 mm line with the words "no pain" and "worst pain possible" on the left and right of it respectively. The position of the mark on the line from the left end to the right will be measured in millimetres to obtain level of dynamic mechanical allodynia (The higher the VAS score the more severe the dynamic mechanical allodynia). The change in dynamic mechanical allodynia will be assessed by comparing the scores obtained on trial day 1 versus day 14 and scores obtained on day 21 versus day 35.
Measured: Scores obtained from tests performed on trial day 1, day 14, day 21 and day 35 will be used.
Secondary outcomes (2)
Analysis of pain relief
Pain relief measured on a 6-point categorical pain relief scale (0-worse pain to 5-complete pain relief). The higher the score the greater the pain relief.
Measured: Scores will be obtained on trial day 14 and day 35.
Change in area of Punctate Hyperalgesia
Area of punctate hyperalgesia will be obtained by marking and calculating the area of sensitivity to punctate stimulation of the skin with a Neuropen. Change in area of punctate hyperalgesia will be obtained by comparing the areas measured on trial day 1 versus trial day 14 and trial day 21 versus trial day 35.
Measured: Measurements will be performed on trial day 1, day 14 , day 21 and day 35.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2017
- Study start19 Feb 2019
- Primary completion12 Oct 2021
- Study completion12 Oct 2021
Why it stopped: Low recruitment due to the COVID-19 pandemic
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Neuralgia PeripheralStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Terence J. Coderre
- Sponsor type
- University, hospital or other
- Collaborators
- The Louise And Alan Edwards Foundation
- Responsible party
- Sponsor-investigator, Terence J. Coderre, McGill University Health Centre/Research Institute of the McGill University Health Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03342950
- Sponsor's protocol ID
- A03-M45-15B
- Acronym
- TTNP
- Status last verified
- Oct 2021
- First submitted
- 1 Nov 2017
- Last updated
- 21 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ragavendran JV, Laferriere A, Xiao WH, Bennett GJ, Padi SS, Zhang J, Coderre TJ. Topical combinations aimed at treating microvascular dysfunction reduce allodynia in rat models of CRPS-I and neuropathic pain. J Pain. 2013 Jan;14(1):66-78. doi: 10.1016/j.jpain.2012.10.004.
PubMed 23273834Ragavendran JV, Laferriere A, Bennett GJ, Ware MA, Gandhi W, Bley K, Schweinhardt P, Coderre TJ. Effects of topical combinations of clonidine and pentoxifylline on capsaicin-induced allodynia and postcapsaicin tourniquet-induced pain in healthy volunteers: a double-blind, randomized, controlled study. Pain. 2016 Oct;157(10):2366-2374. doi: 10.1097/j.pain.0000000000000659.
PubMed 27385502Brown MB, Martin GP, Jones SA, Akomeah FK. Dermal and transdermal drug delivery systems: current and future prospects. Drug Deliv. 2006 May-Jun;13(3):175-87. doi: 10.1080/10717540500455975.
PubMed 16556569Li C, Sekiyama H, Hayashida M, Takeda K, Sumida T, Sawamura S, Yamada Y, Arita H, Hanaoka K. Effects of topical application of clonidine cream on pain behaviors and spinal Fos protein expression in rat models of neuropathic pain, postoperative pain, and inflammatory pain. Anesthesiology. 2007 Sep;107(3):486-94. doi: 10.1097/01.anes.0000278874.78715.1d.
PubMed 17721252Palos GR, Mendoza TR, Cantor SB, Aday LA, Cleeland CS. Perceptions of analgesic use and side effects: what the public values in pain management. J Pain Symptom Manage. 2004 Nov;28(5):460-73. doi: 10.1016/j.jpainsymman.2004.02.016.
PubMed 15504623Fulas OA, Laferriere A, Ware DMA, Shir Y, Coderre TJ. 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. 2021 Feb 17;22(1):149. doi: 10.1186/s13063-021-05088-w.
PubMed 33596969
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Topical Treatment With Clonidine + Pentoxifylline in Patients With Neuropathic Pain
- ClinicalTrials.gov ID
- NCT03342950
- Acronym / sponsor ID
- TTNP / A03-M45-15B
- Conditions
- Neuralgia Peripheral
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low recruitment due to the COVID-19 pandemic
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Terence J. CoderreUniversity, hospital or other
- Collaborators
- The Louise And Alan Edwards Foundation
- Study start
- 19 Feb 2019 (actual)
- Primary completion
- 12 Oct 2021 (actual)
- Study completion
- 12 Oct 2021 (actual)
- First posted
- 17 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Microvascular dysfunction underlies pain in different animal models of neuropathic pain. Pentoxifylline is a phosphodiesterase inhibitor that reduces cyclic adenosine monophosphate (cAMP) hydrolysis, enhances blood flow and reduces platelet aggregation, decreases blood viscosity, and increases the flexibility of red blood cells, all of which relieve microvascular dysfunction. Clonidine is an α2-adrenergic receptor agonist that decreases sympathetic outflow from the brainstem, vascular reactivity and has direct peripheral vasodilatory action. Topical combination of pentoxifylline and clonidine produced significant antiallodynic effects in rat models of neuropathic pain with sciatic nerve injury, painful diabetic neuropathy, and chemotherapy-induced painful neuropathy. In healthy volunteers with an experimentally-induced surrogate for neuropathic pain: post-capsaicin tourniquet exposure, the topical combination reduced areas of dynamic allodynia and mechanical hyperalgesia, in addition to reducing post-capsaicin ischemic pain.
This study will investigate if the same topical combination of clonidine + pentoxifylline will relieve pain in patients with neuropathic pain following traumatic injuries of peripheral nerves.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active drug group | Active comparator | Drug: Topical SolutionTreatment with the topical solution of clonidine + pentoxifylline (0.1%/5%) |
| Placebo group | Placebo comparator | Drug: PlacebosTreatment with placebo solution with out active drug ingredients |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Female or male patients, aged 18-70;
- An average spontaneous pain level of at least 4 on an 11-point numerical rating pain score (0= no pain, 10= worst pain possible) on at least 3 days during the week prior to the study;
- The existence of tactile allodynia, as a sign of chronic pain, following a traumatic peripheral nerve injury;
- Ability to communicate in English or in French;
- Willing and able to sign an informed consent;
Key exclusion criteria (11 listed)
- Diabetes mellitus necessitating antihyperglycemic treatment or any other endocrine disease;
- Any liver disease, resulting in aspartate aminotransferase (AST) levels greater than 3 times the normal values, or kidney disease, resulting in creatinine levels greater than 133 µmol/L;
- Hypertension or taking of anti-hypertensive medication;
- Malignant disease or taking of chemotherapeutic agents;
- Known diagnosis of angina pectoris, arrhythmias, congestive heart failure or peripheral arterial disease;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Topical SolutionTopical Solution of Clonidine (0.01%) + Pentoxifylline (5%) in anhydrous ethanol (6.5%), polyethylene glycol 400 (20%), propylene glycol (53.5%), and oleyl alcohol (20%) | Drug | Active drug group |
| PlacebosTopical Solution of anhydrous ethanol (6.5%), polyethylene glycol 400 (20%), propylene glycol (53.5%), and oleyl alcohol (20%) | Drug | Placebo group |
Primary outcome
Change in visual analogue scale (VAS) score of spontaneous pain intensity
Time frame: Scores recorded on pain diary on trial day 1, day 14 , day 21 and day 35 will be used
This will be an evaluation of patients' daily spontaneous pain recorded on a pain diary. The visual analogue scale is a 100 millimetre line with the words "no pain" and "worst pain possible" on the left and right of it respectively. The patients will indicate their level of pain by marking on the line. The position of the mark on the line from the left end to the right will be measured in millimetres to obtain level of pain severity (The higher the VAS score the more severe the pain) . Change in VAS score will be obtained by comparing the difference between scores recorded on trial day 1 versus trial day 14 and trial day 21 versus trial day 35.
Change in visual analogue scale (VAS) score of dynamic mechanical allodynia (DMA)
Time frame: Scores obtained from tests performed on trial day 1, day 14, day 21 and day 35 will be used.
The degree of dynamic mechanical allodynia will be determined by stroking the most painfully sensitive area of the skin three times over 5 seconds at a rate of 1-2 cm/s with a Somedic brush. The patient will indicate the amount of pain evoked on a 100-millimeter visual analogue scale (VAS) by marking on a 100 mm line with the words "no pain" and "worst pain possible" on the left and right of it respectively. The position of the mark on the line from the left end to the right will be measured in millimetres to obtain level of dynamic mechanical allodynia (The higher the VAS score the more severe the dynamic mechanical allodynia). The change in dynamic mechanical allodynia will be assessed by comparing the scores obtained on trial day 1 versus day 14 and scores obtained on day 21 versus day 35.
2 secondary outcomes
Analysis of pain relief
Time frame: Scores will be obtained on trial day 14 and day 35.
Change in area of Punctate Hyperalgesia
Time frame: Measurements will be performed on trial day 1, day 14 , day 21 and day 35.
Results and safety
The study was stopped early (reason given: Low recruitment due to the COVID-19 pandemic). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2021.
- Background: PubMed 23273834Ragavendran JV, Laferriere A, Xiao WH, Bennett GJ, Padi SS, Zhang J, Coderre TJ. Topical combinations aimed at treating microvascular dysfunction reduce allodynia in rat models of CRPS-I and neuropathic pain. J Pain. 2013 Jan;14(1):66-78. doi: 10.1016/j.jpain.2012.10.004.
- Background: PubMed 27385502Ragavendran JV, Laferriere A, Bennett GJ, Ware MA, Gandhi W, Bley K, Schweinhardt P, Coderre TJ. Effects of topical combinations of clonidine and pentoxifylline on capsaicin-induced allodynia and postcapsaicin tourniquet-induced pain in healthy volunteers: a double-blind, randomized, controlled study. Pain. 2016 Oct;157(10):2366-2374. doi: 10.1097/j.pain.0000000000000659.
- Background: PubMed 16556569Brown MB, Martin GP, Jones SA, Akomeah FK. Dermal and transdermal drug delivery systems: current and future prospects. Drug Deliv. 2006 May-Jun;13(3):175-87. doi: 10.1080/10717540500455975.
- Background: PubMed 17721252Li C, Sekiyama H, Hayashida M, Takeda K, Sumida T, Sawamura S, Yamada Y, Arita H, Hanaoka K. Effects of topical application of clonidine cream on pain behaviors and spinal Fos protein expression in rat models of neuropathic pain, postoperative pain, and inflammatory pain. Anesthesiology. 2007 Sep;107(3):486-94. doi: 10.1097/01.anes.0000278874.78715.1d.
- Background: PubMed 15504623Palos GR, Mendoza TR, Cantor SB, Aday LA, Cleeland CS. Perceptions of analgesic use and side effects: what the public values in pain management. J Pain Symptom Manage. 2004 Nov;28(5):460-73. doi: 10.1016/j.jpainsymman.2004.02.016.
- Derived from this study: PubMed 33596969Fulas OA, Laferriere A, Ware DMA, Shir Y, Coderre TJ. 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. 2021 Feb 17;22(1):149. doi: 10.1186/s13063-021-05088-w.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Topical Solution in people with Neuralgia Peripheral, run by Terence J. Coderre at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Low recruitment due to the COVID-19 pandemic). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in visual analogue scale (VAS) score of spontaneous pain intensity (time frame: Scores recorded on pain diary on trial day 1, day 14 , day 21 and day 35 will be used). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03342950, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2021.