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

Terence J. Coderre

Status and phase: Terminated; Phase 2

Conditions: Neuralgia Peripheral

Treatments: Drug: Placebos; Drug: Topical Solution

Study type: Interventional

Funder types: Other

Identifiers

NCT03342950

A03-M45-15B

Details and patient eligibility

About

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.

Enrollment: 4 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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4 participants in 2 patient groups, including a placebo group

Active drug group

Active Comparator group

Description:

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

Treatment:

Drug: Topical Solution

Placebo group

Placebo Comparator group

Description:

Treatment with placebo solution with out active drug ingredients

Treatment:

Drug: Placebos