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The purpose of this study is to determine if minocycline is effective in the treatment of neuropathic pain. The effect of minocycline will be compared to the effect of placebo and amitriptyline.
Neuropathic pain is pain caused by damage to the central or peripheral nervous system. To date, therapy consists of tricyclic antidepressants (such as amitriptyline) or anticonvulsants. However, results are disappointing. Minocycline, a FDA-approved second generation tetracycline, was efficacious in various animal models of neuropathic pain. We want to study the effect of minocycline in neuropathic pain in humans. The type of neuropathic pain we want to investigate is lumbar radicular pain since this is the most prevalent condition associated with neuropathic pain in humans.
This placebo-controlled randomized double blind trial consists of 3 arms:
Patients can take rescue medication if necessary: tramadol 50mg by mouths up to 3-times daily.
Brain-derived neurotrophic factor is implicated in the generation and maintenance of neuropathic pain in different animal models of neuropathic pain. To study the role of brain-derived neurotrophic factor in neuropathic pain in humans, we will determine its concentration in serum and plasma before and after 14 days medication intake.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Placebo, once daily |
|
| Amitriptyline | Active Comparator | Amitriptyline 25mg, once daily |
|
| Minocycline | Active Comparator | Minocycline 100mg, once daily |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Minocycline | Drug | 100 mg once daily by mouth during 14 days |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Pain intensity | Pain intensity will be measured using a visual analogue scale and the change in pain intensity between baseline and day 7, day 7 and day 14, baseline and day 14 will be evaluated | Baseline (before start of study), 7 and 14 days after start of medication intake |
| Measure | Description | Time Frame |
|---|---|---|
| neuropathic pain diagnostic questionnaire (DN4) score | The DN4 questionnaire is used to assess the neuropathic symptoms of the pain and the change in DN4 score between baseline and day 7, day 7 and day 14, baseline and day 14 will be evaluated | Baseline (before start of study), 7 and 14 days after medication intake |
| Measure | Description | Time Frame |
|---|---|---|
| Concentration of brain-derived neurotrophic factor (BDNF) in serum and plasma | A blood sample (10ml) will be taken at baseline and after 14 days medication intake. The concentration of brain derived neurotrophic factor will be determined by high sensitivity ELISA (R&D systems® Europe, United Kingdom; detection range: 20-4,000 pg/ml) and the change in BDNF-concentration in serum and plasma between baseline and day 14 will be evaluated. |
Inclusion Criteria:
Lumbar radicular pain due to disc herniation, failed back surgery syndrome or spinal canal stenosis causing neuropathic pain
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jan Van Zundert, MD, PhD | Ziekenhuis Oost-Limburg | Study Chair |
| Martine Puylaert, MD | Ziekenhuis Oost-Limburg | Study Chair |
| Pieter De Vooght, MD | Ziekenhuis Oost-Limburg | Study Chair |
| Roel Mestrum, MD | Ziekenhuis Oost-Limburg | Study Chair |
| René Heylen, MD, PhD | Ziekenhuis Oost-Limburg | Study Chair |
| Pascal Vanelderen, MD | Ziekenhuis Oost-Limburg | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ziekenhuis Oost-Limburg | Genk | Limburg | 3600 | Belgium |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23337936 | Result | Vanelderen P, Rouwette T, Kozicz T, Heylen R, Van Zundert J, Roubos EW, Vissers K. Effects of chronic administration of amitriptyline, gabapentin and minocycline on spinal brain-derived neurotrophic factor expression and neuropathic pain behavior in a rat chronic constriction injury model. Reg Anesth Pain Med. 2013 Mar-Apr;38(2):124-30. doi: 10.1097/AAP.0b013e31827d611b. | |
| 22282331 |
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| ID | Term |
|---|---|
| D008911 | Minocycline |
| D000639 | Amitriptyline |
| ID | Term |
|---|---|
| D013754 | Tetracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
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| placebo |
| Drug |
once daily by mouth during 14 days |
|
| Amitriptyline | Drug | 25mg once daily by mouth during 14 days |
|
| Amount of rescue medication taken |
Rescue medication consists of tramadol 50mg by mouth 3-times daily if necessary. Patients will be provided with a total of 42 tablets of tramadol 50mg for the duration of the study. The remaining rescue medication will be counted on day 7 and day 14 and the change in rescue medication intake between baseline and day 7, day 7 and day 14, baseline and day 14 will be evaluated |
| 7 and 14 days after medication intake |
| Baseline (before start of study) and after 14 days of medication intake. |
| Result |
| Bastos LF, de Oliveira AC, Watkins LR, Moraes MF, Coelho MM. Tetracyclines and pain. Naunyn Schmiedebergs Arch Pharmacol. 2012 Mar;385(3):225-41. doi: 10.1007/s00210-012-0727-1. Epub 2012 Jan 27. |
| 19467572 | Result | Zhang Q, Peng L, Zhang D. Minocycline may attenuate postherpetic neuralgia. Med Hypotheses. 2009 Nov;73(5):744-5. doi: 10.1016/j.mehy.2009.04.028. Epub 2009 May 24. |
| 22685578 | Result | Sumracki NM, Hutchinson MR, Gentgall M, Briggs N, Williams DB, Rolan P. The effects of pregabalin and the glial attenuator minocycline on the response to intradermal capsaicin in patients with unilateral sciatica. PLoS One. 2012;7(6):e38525. doi: 10.1371/journal.pone.0038525. Epub 2012 Jun 7. |
| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| D003986 | Dibenzocycloheptenes |
| D001567 | Benzocycloheptenes |