Effect of Minocycline on Pain Caused by Nerve Damage

Study Overview
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Brief Summary
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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.

Detailed Description
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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: Placebo, once daily by mouth during 14 days. Amitriptyline 25mg, once daily by mouth during 14 days. Minocycline 100mg, once daily by mouth during 14 days. 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.

Official Title
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Effect of Minocycline on Neuropathic Pain

Conditions
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Neuropathic Pain Caused by Lumbar Radicular Pain

Intervention / Treatment
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* Drug: Minocycline
* Drug: placebo
* Drug: Amitriptyline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Lumbar radicular pain due to disc herniation, failed back surgery syndrome or spinal canal stenosis causing neuropathic pain Exclusion Criteria: Diabetic, alcoholic or drug induced polyneuropathies Depression or psychiatric comorbidity affecting pain sensation. Use of antidepressants Fibromyalgia and Chronic Fatigue Syndrome Pregnancy. Previous spinal cord damage Malignancies Allergy to minocycline or amitriptyline

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo, once daily | Drug: placebo<br>* once daily by mouth during 14 days<br>|
| Active Comparator: Amitriptyline<br>Amitriptyline 25mg, once daily | Drug: Amitriptyline<br>* 25mg once daily by mouth during 14 days<br>|
| Active Comparator: Minocycline<br>Minocycline 100mg, once daily | Drug: Minocycline<br>* 100 mg once daily by mouth during 14 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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 | 
| 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 |