The Effects of Topical Treatment With Clonidine + Pentoxifylline in Patients With Neuropathic Pain

NCT ID: NCT03342950

Last Updated: 2021-10-21

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-19
• Study Completion Date: 2021-10-12

Brief 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 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Active drug group

Treatment with the topical solution of clonidine + pentoxifylline (0.1%/5%)

Group Type: ACTIVE_COMPARATOR

Topical Solution

Intervention Type: DRUG

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%)

Placebo group

Treatment with placebo solution with out active drug ingredients

Group Type: PLACEBO_COMPARATOR

Placebos

Intervention Type: DRUG

Topical Solution of anhydrous ethanol (6.5%), polyethylene glycol 400 (20%), propylene glycol (53.5%), and oleyl alcohol (20%)

Interventions

Topical Solution

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%)

Intervention Type: DRUG

Placebos

Topical Solution of anhydrous ethanol (6.5%), polyethylene glycol 400 (20%), propylene glycol (53.5%), and oleyl alcohol (20%)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Female or male patients, aged 18-70;

2. 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;

3. The existence of tactile allodynia, as a sign of chronic pain, following a traumatic peripheral nerve injury;

4. Ability to communicate in English or in French;

5. Willing and able to sign an informed consent;

6. Stable pain disease with no anticipated change in treatment in the next 5 weeks.

7. 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.

Exclusion Criteria

1. Diabetes mellitus necessitating antihyperglycemic treatment or any other endocrine disease;

2. 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;

3. Hypertension or taking of anti-hypertensive medication;

4. Malignant disease or taking of chemotherapeutic agents;

5. Known diagnosis of angina pectoris, arrhythmias, congestive heart failure or peripheral arterial disease;

6. Pregnancy or breast feeding. Female patients of child-bearing age must have a negative urine pregnancy test;

7. Known allergic reaction to clonidine or pentoxifylline;

8. Presence of major depression, bipolar affective disorder or schizophrenia;

9. Presence of a severe medical condition, or condition known to affect peripheral circulation (intermittent claudication, peripheral arterial disease, Raynaud's syndrome);

10. 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];

11. 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Louise And Alan Edwards Foundation

UNKNOWN

Sponsor Role: collaborator

Terence J. Coderre

OTHER

Sponsor Role: lead

Responsible Party

Terence J. Coderre

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

McGill University

Montreal, Quebec, Canada

Countries

Canada

References

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Reference Type: BACKGROUND

PMID: 23273834 (View on PubMed)

Ragavendran 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.

Reference Type: BACKGROUND

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Reference Type: BACKGROUND

PMID: 16556569 (View on PubMed)

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

PMID: 15504623 (View on PubMed)

Fulas 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.

Reference Type: DERIVED

PMID: 33596969 (View on PubMed)

Other Identifiers

A03-M45-15B

Identifier Type: -

Identifier Source: org_study_id