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

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.

Study Overview

• Status: Unknown
• Conditions: Fibromylagia
• Intervention / Treatment: Drug: Placebo; Drug: Milnacipran

Detailed Description

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

• Study Type: Interventional
• Enrollment (Anticipated): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Clermont-Ferrand, France, 63003
    • Recruiting
    • CHU de Clermont-Ferrand

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Milnacipran; 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; 100mg/day
Placebo Comparator: Capsules of lactose; placebo over a period of 8 weeks to 24 weeks	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand
• Collaborators: Dr. Gisèle PICKERING (MCU, PH) Center of clinical pharmacology/CIC Inserm-501 - Main investigator; Dr Pascale PICARD/ Dr Noémie Delage / Dr Fabienne RIAUX - Center of evaluation and treatment of the pain - Investigator; Dr Gilles DUCHEIX/ Center of clinical pharmacology/CIC Inserm-501 - Investigator; Dr Christian DUALE/ Center of clinical pharmacology/CIC Inserm-501 - Investigator

Publications and helpful links

General Publications

• Macian N, Pereira B, Shinjo C, Dubray C, Pickering G. Fibromyalgia, milnacipran and experimental pain modulation: study protocol for a double blind randomized controlled trial. Trials. 2015 Apr 3;16:134. doi: 10.1186/s13063-015-0659-4.

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Anticipated): November 1, 2014
• Study Completion (Anticipated): November 1, 2014

Study Registration Dates

• First Submitted: November 27, 2012
• First Submitted That Met QC Criteria: December 10, 2012
• First Posted (Estimate): December 11, 2012

Study Record Updates

• Last Update Posted (Estimate): July 8, 2014
• Last Update Submitted That Met QC Criteria: July 4, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: Fibromyalgia; Milnacipran; Diffuse Noxious Inhibitory Controls
• Additional Relevant MeSH Terms: Nervous System Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Muscular Diseases; Neuromuscular Diseases; Fibromyalgia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Serotonin and Noradrenaline Reuptake Inhibitors; Milnacipran; Levomilnacipran
• Other Study ID Numbers: CHU-0130