Effect of Minocycline on Pain Caused by Nerve Damage (EMON)

Effect of Minocycline on Neuropathic Pain

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.

Study Overview

• Status: Completed
• Conditions: Neuropathic Pain Caused by Lumbar Radicular Pain
• Intervention / Treatment: Drug: placebo; Drug: Amitriptyline; Drug: Minocycline

Detailed Description

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:

1. Placebo, once daily by mouth during 14 days.
2. Amitriptyline 25mg, once daily by mouth during 14 days.
3. 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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Limburg
    • Genk, Limburg, Belgium, 3600
      • Ziekenhuis Oost-Limburg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Lumbar radicular pain due to disc herniation, failed back surgery syndrome or spinal canal stenosis causing neuropathic pain

Exclusion Criteria:

1. Diabetic, alcoholic or drug induced polyneuropathies
2. Depression or psychiatric comorbidity affecting pain sensation.
3. Use of antidepressants
4. Fibromyalgia and Chronic Fatigue Syndrome
5. Pregnancy.
6. Previous spinal cord damage
7. Malignancies
8. Allergy to minocycline or amitriptyline

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo, once daily	Drug: placebo; once daily by mouth during 14 days
Active Comparator: Amitriptyline; Amitriptyline 25mg, once daily	Drug: Amitriptyline; 25mg once daily by mouth during 14 days
Active Comparator: Minocycline; Minocycline 100mg, once daily	Drug: Minocycline; 100 mg once daily by mouth during 14 days

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	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.	Baseline (before start of study) and after 14 days of medication intake.

Collaborators and Investigators

• Sponsor: Ziekenhuis Oost-Limburg
• Investigators: Study Chair: 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; Principal Investigator: Pascal Vanelderen, MD, Ziekenhuis Oost-Limburg

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: May 27, 2013
• First Submitted That Met QC Criteria: June 2, 2013
• First Posted (Estimate): June 5, 2013

Study Record Updates

• Last Update Posted (Estimate): January 27, 2015
• Last Update Submitted That Met QC Criteria: January 24, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Neuromuscular Diseases; Peripheral Nervous System Diseases; Neuralgia; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Anti-Bacterial Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Antidepressive Agents, Tricyclic; Adrenergic Uptake Inhibitors; Amitriptyline; Minocycline
• Other Study ID Numbers: EMON