Prospective Study of the Influence of the Diffuse Noxious Inhibitory Controls of the Pain on the Efficacy of Milnacipran in Fibromyalgia Therapy

Study Overview
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Brief Summary
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Fibromyalgia affects 0.7 to 3.3% of the adult population and 7-10 times more women than men. In France, the prevalence is 1.6% according to a French study conducted in 2009 and published in 2011 by Serge Perrot et al. The definition of fibromyalgia was recently amended with particular consideration of cognitive and somatic symptoms, factors not involved in the initial criteria of the ACR classification. Several factors are in favor of a malfunction of the central modulation of pain and poorer performance noxious inhibitory controls descendants (DNIC: diffuse noxious inhibitory controls) have been demonstrated. In fibromyalgia patients, the DNIC (diffuse noxious inhibitory controls) are altered with less pain inhibition than controls. Dysfunction of the central pain modulation is widely described in the literature and contributes to pain complained of fibromyalgia. According to the Recommendations of the European League Against Rheumatism (EULAR) 2006, antidepressants have a genuine analgesic efficacy in controlled studies. Milnacipran is an antidepressant known and used in major depressive disorder according to its marketing authorization but is also part of the molecules used in the treatment of chronic neuropathic pain and fibromyalgia according to the recommendations of the EULAR. A review included five double-blind studies on 4,000 participants who took 100 mg or 200 mg milnacipran or placebo over a period of 8 weeks to 24 weeks. A moderate response was obtained for 40% of participants treated for each dose of milnacipran on the criteria of at least 30% pain relief Impression and global change. Substantial improvement with milnacipran compared to placebo has been shown. To date, the link between the weakening of DNIC in fibromyalgia and effectiveness of drug treatment has not been shown. This study aims to assess the degree of impairment of DNIC in fibromyalgia patients may be predictive of the efficacy of milnacipran.

Detailed Description
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Visit 1 Inclusion of the patient, Clinical examination, Evaluation of pain, basal Pain and cognitive tests Visit 2 (can be coupled with Visit 1 if necessary) Randomisation of the patient and allocation of the treatment for 1 month. Phone contact Visit 2 +7 days, + 15 days, +21 days Follow-up of the compliance of the treatment and collection of adverse events. Visit 3 (follow up at 1 month) Evaluation of pain, Pain and cognitive tests End of study

Conditions
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Fibromylagia

Intervention / Treatment
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* Drug: Milnacipran
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient of more than 18 years old, Patient with fibromyalgia Exclusion Criteria: Patient with a contraindication to the administration of the milnacipran, Patient with a concomitant spontaneous pain not attributable of fibromyalgia, Patient with medical and/or surgical histories judged by the investigator not compatible with the trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Milnacipran<br>Milnacipran is an antidepressant known and used in major depressive disorder according to its marketing authorization but is also part of the molecules used in the treatment of chronic neuropathic pain and fibromyalgia according to the recommendations of the EULAR | Drug: Milnacipran<br>* 100mg/day<br>|
| Placebo Comparator: Capsules of lactose<br>placebo over a period of 8 weeks to 24 weeks | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain scores on the verbal numeric scale |  | at T0 and T0+1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| sensitivity and pain thresholds to a mechanical stimulus |  | at T0 and T0+1 month | 
| sensitivity and pain thresholds to a thermal stimulus |  | at T0 and T0+1 month | 
| scores on cognitive tests |  | at T0 and T0+1 month | 
| Adverse events record |  | at T0 and T0+1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fibromyalgia, Diffuse Noxious Inhibitory Controls, Milnacipran