A Placebo Controlled, Randomized, Double Blind Trial of Milnacipran for the Treatment of Idiopathic Neuropathy Pain

This is an 11-week randomized, double-blind, placebo-controlled trial of Milnacipran 100 mg/d in patients with idiopathic neuropathic pain. Milnacipran, a dual norepinephrine and serotonin reuptake inhibitor has been a safe and beneficial treatment for patients with fibromyalgia and may be useful to treat patients with painful peripheral neuropathy.

The primary outcome will be assessed by the change in daily averaged weekly 0-10 pain intensity score, from baseline to week 9, by intention to treat analysis. The same analysis will be used on several secondary measures including daily averaged weekly 0-10 pain intensity score the sleep interference scale and the Rand-36 quality of life scale.

Study Overview

• Status: Terminated
• Conditions: Idiopathic Peripheral Neuropathy
• Intervention / Treatment: Drug: Milnacipran; Drug: Placebo

Detailed Description

Milnacipran helps serotonin and noradrenaline work more effectively on the central nervous system. Serotonin and noradrenaline are molecules made by the brain that affect how your body responds to pain. Milnacipran, a dual norepinephrine and serotonin reuptake inhibitor has been a safe and beneficial treatment for patients with fibromyalgia and may be useful to treat patients with painful peripheral neuropathy. Many clinical trials for neuropathy pain are done in patients with diabetic neuropathy. Idiopathic neuropathy however, is a common cause of neuropathy and accounts for 25% of all neuropathies, and over 50% of small fiber neuropathies. The information in this study will provide information on whether milnacipran also provide benefit as a medication for neuropathic pain.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female patients age 18 to 80 years
• Patients with signs and symptoms of a peripheral neuropathy, with either abnormal nerve conductions or abnormal epidermal nerve fiber density with neuropathic pain.
• Pain will have been present for at least 6 months
• Patients may be on other medications for neuropathic pain (eg, antiepileptic medications, opiates or non steroidal antiinflammatories); however they must be on a stable dose for 4 weeks prior to, with no plan to change during the study
• All patients must have had a normal fasting glucose or B12, thyroid stimulating hormone, and serum protein electrophoresis, since the onset of their symptoms.

Exclusion Criteria:

• Other cause of neuropathy (eg, diabetic neuropathy, toxic neuropathy, HIV neuropathy, celiac neuropathy, inherited neuropathy)
• Unstable angina
• Use of another serotonin and norepinephrine reuptake inhibitors (eg, duloxetine, venlafaxine), tricyclic antidepressants, monoamine oxidase inhibitors (MAOI) or selective serotonin reuptake inhibitors
• Myocardial infarction stroke or life threatening arrhythmia within the last 6 months
• HIV infection
• Hepatic or renal failure
• Pregnancy
• narrow angle glaucoma
• History of epilepsy or a seizure

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Milnacipran; Patients will receive Milnacipran	Drug: Milnacipran; Patients will be randomly assigned to receive milnacipran 100 mg/day (including a 1 week dose titration period): Day 1: 12.5 mg once Day 2, 3: 25 mg/day (12.5 mg twice daily) Day 4, 7: 50 mg/day (25 mg twice daily) After Day 7: 100 mg/day (50 mg twice daily); Other Names: Savella
Placebo Comparator: Placebo; Patients will receive Placebo	Drug: Placebo; Patients will be randomly assigned to placebo for 9 weeks (including a 1 week dose titration period), matching the schedule of the study drug.; Other Names: Placebo Pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Likert Pain Scale Score	The Likert Pain Scale Score is a psychometric scale commonly involved in research that employs questionnaires to measure the intensity of pain. It is used to determine the level of pain for research participants. The minimum score of 0 indicates "no pain" which is the better score and the maximum and total score of 10 indicates the "the worst possible pain" which is the worse outcome . Scores 1-3= Mild, scores 4-6= Moderate, scores 7-10= Severe. It is the most widely used approach to scaling responses in survey research. Patients will fill out a pain diary from baseline to end of treatment. This will be used to assess if there was a reduction in pain of the daily averaged weekly 0-10 pain scale at week 9 compared to the baseline. The Unit of Measure is the scores on the scale.	Baseline, 9 weeks

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: Forest Laboratories
• Investigators: Principal Investigator: Thomas H Brannagan III, MD, Columbia University

Study record dates

Study Major Dates

• Study Start (Actual): April 5, 2011
• Primary Completion (Actual): October 22, 2014
• Study Completion (Actual): December 23, 2014

Study Registration Dates

• First Submitted: February 1, 2011
• First Submitted That Met QC Criteria: February 2, 2011
• First Posted (Estimate): February 3, 2011

Study Record Updates

• Last Update Posted (Actual): September 3, 2020
• Last Update Submitted That Met QC Criteria: August 19, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Neuropathic pain; Diabetic neuropathy; Milnacipran; Idiopathic Peripheral Neuropathy
• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; 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: AAAF3404

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No