Effects of Milnacipran on Widespread Mechanical and Thermal Hyperalgesia of Fibromyalgia Patients

Fibromyalgia syndrome (FM) shares many symptoms common to chronic neuropathic pain, including the characteristic hyperalgesia of the skin (thermal, mechanical) and muscles (mechanical) found in almost all FM patients. Milnacipran, a balance norepinephrine-serotonin re-uptake inhibitor, has been found to reduce pain and improve physical function of FM patients. However, little is known about the pain mechanisms that are affected by this medication. Therefore, the investigator wants to determine the efficacy of milnacipran in reducing pain as well as mechanical and thermal hyperalgesia of FM patients during a randomized, double-blind, placebo controlled trial. Because the investigator expects anti-hyperalgesic effects to coincide or precede with effects on clinical FM pain the proposed duration for this trial is 6 weeks.

Study Overview

• Status: Completed
• Conditions: Fibromyalgia
• Intervention / Treatment: Drug: Milnacipran

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • Center for Musculoskeletal Pain Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with diagnosis of chronic wide-spread pain for at least 3 months, who fulfill the 1990 ACR Criteria for FM.
2. Patients with mean pain ratings ≥ 4.0 VAS units, at Screening and Baseline visits.
3. Patients, who are able to comprehend and satisfactorily comply with protocol requirements.
4. Patients who have not taken any pain medications except acetaminophen within 3 days prior to the Baseline Visit (these medications if taken prior to the Screening Visit must be discontinued at Screening Visit and the Baseline Visit may be scheduled at least 7 days past the last dose of these medications).
5. All women of childbearing potential (WOCBP) must have a negative urine pregnancy test at the Screening Visit. All women of childbearing potential participating in the study must use a medically acceptable form of contraception

Exclusion Criteria:

1. FM patients unwilling or unable to discontinue analgesics (except Tylenol) for at least 5 drug half-lives prior to enrollment.
2. Patient has previously failed treatment with Milnacipran for FM pain.
3. Patients who have been treated with MAO inhibitors within 30 days prior to the Baseline Visit.
4. Patients who received ECT within 3 months prior to the Screening Visit.
5. Women who are pregnant or nursing, or women of childbearing potential who do not use adequate contraception, or who are judged to be unreliable in their use of contraception.
6. Patients who have participated in any clinical trial within one month prior to the Screening Visit.
7. Patients who have a medical condition that, in the Investigator's opinion, would expose them to an increased risk of a significant adverse event or interfere with assessments of safety and efficacy during the course of the trial.
8. Patients with severe renal insufficiency (Creatinine clearance < 30 ml/min)
9. Patient has a BDI score >29
10. Patients with any current malignancy, or any clinically significant hematological, endocrine, cardiovascular, renal, hepatic, gastrointestinal or neurological disease (including any form of epilepsy). If there is a history of such disease but the condition has been stable for at least the past year and is judged by the investigator not to interfere with the patient's participation in the study, the patient may be included.
11. Patients with systolic blood pressure greater than 180 mm Hg or less than 90 mm Hg or diastolic blood pressure greater than 105 mm Hg or less than 50 mm Hg at the Screening visit. Similarly, tachycardia of >110/min is exclusionary.
12. Patients who require concomitant therapy with any prohibited prescription or over-the-counter medication, including aspirin (except 81 mg for heart disease) or antidepressant medications.
13. Patients who are unable to speak, read, and understand English or are judged by the investigator to be unable or unlikely to follow the study protocol and complete all scheduled visits.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Sugar pill; One sugar pill twice daily over 6 weeks	Drug: Milnacipran; 50 mg BID Oral x 6 Weeks; Other Names: Savella
Active Comparator: Milnacipran; Milnacipran 50 mg bid over 6 weeks	Drug: Milnacipran; 50 mg BID Oral x 6 Weeks; Other Names: Savella

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mechanical and Heat Hyperalgesia	2 week intervals

Secondary Outcome Measures

Outcome Measure	Time Frame
Clinical Pain	daily

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: Forest Laboratories

Publications and helpful links

General Publications

• Staud R, Lucas YE, Price DD, Robinson ME. Effects of milnacipran on clinical pain and hyperalgesia of patients with fibromyalgia: results of a 6-week randomized controlled trial. J Pain. 2015 Aug;16(8):750-9. doi: 10.1016/j.jpain.2015.04.010. Epub 2015 May 19.

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: February 9, 2011
• First Submitted That Met QC Criteria: February 9, 2011
• First Posted (Estimate): February 11, 2011

Study Record Updates

• Last Update Posted (Estimate): July 31, 2014
• Last Update Submitted That Met QC Criteria: July 29, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: Pain; Fibromyalgia; Hyperalgesia; Central Sensitization
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Musculoskeletal Diseases; Rheumatic Diseases; Muscular Diseases; Neuromuscular Diseases; Sensation Disorders; Somatosensory Disorders; Fibromyalgia; Myofascial Pain Syndromes; Hyperalgesia; 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: SAV-MD-06