Milnacipran for Lumbosacral Radicular Pain

Study Overview
=================
Brief Summary
-----------------
This study investigates whether milnacipran reduces radicular pain (sciatica) in patients with lumbosacral disc disease.

Detailed Description
-----------------
The current study evaluates the potential efficacy of milnacipran in reducing lower extremity radicular pain associated with lumbar disk disease. Milnacipran will be titrated based on efficacy and tolerability aimed at the higher end of the therapeutic range; a recent study of a serotonin norepinephrine reuptake inhibitor in patients with osteoarthritis pain suggests efficacy may be dose related. Patients are likely to have concomitant nociceptive lower back pain, and cotreatment with opioids, muscle relaxants, benzodiazepines, or nonsteroidal anti-inflammatory drugs at stable doses will be permitted. Patients participating in stable regimen of physical therapy or biofeedback will be eligible. Procedural interventions (e.g. epidural steroid injection, nerve block, facet radioablation, acupuncture) during the study and 3 months prior will be exclusionary. Anticonvulsants, tramadol, and other antidepressant drugs will be excluded. The study is a ten-week randomized, double-blind, placebo-controlled trial (RCT) of milnacipran (100-200 mg/day dosed twice a day) for radicular pain associated with lumbosacral disk disease. Outcome measures and safety assessments will be obtained at weeks 1, 2, 4, 6, 8, and 10 according to the protocol schedule of assessments.

Official Title
-----------------
A Ten-Week, Randomized, Double-Blind, Placebo-Controlled Parallel-Group Study of Milnacipran for Radicular Pain Associated With Lumbosacral Disk Disease

Conditions
-----------------
Radicular Pain Related to Lumbosacral Disc Disease

Intervention / Treatment
-----------------
* Drug: Milnacipran
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject is a male or female adult outpatient age 18 or older at the time of consent. Subject experiences chronic (> 6 months) radicular pain at least 5 days a week described as sharp or shooting below the level of the knee associated with lumbar or sacral disk disease without suspicion of recent injury; remote (>1 year ago) history of surgical intervention (e.g. failed back syndrome) is allowed provided current symptoms meet severity criterion. Subject-rated VAS specifically related to radicular pain > or = 40 mm at screen and baseline visits Subject has an understanding, ability and willingness to fully comply with study procedures and restrictions. Subject has the ability to provide written, personally signed and dated informed consent to participate in the study, in accordance with the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) Guideline E6 and applicable regulations, before completing any study-related procedures. Exclusion Criteria: Subjects unable to complete assessments due to language or cognitive impairment Subjects treated with antidepressant or anticonvulsant medication within 4 weeks of screening visit (6 weeks for fluoxetine). Subjects taking monoamine oxidase inhibitors Subjects who have received procedural intervention within 3 months of screen. Subjects with known sensitivity to milnacipran. Subjects unable to complete the questionnaires due to language or cognitive impairment. Subjects with a history of bipolar disorder or psychosis as confirmed by the Mini International Neuropsychiatric Interview (MINI). Subject currently has (or had a history within the last 6 months of) a drug dependence or substance abuse disorder according to Diagnostic and Statistical Manual for Mental Disorders, Text Revision criteria (excluding nicotine). Subjects who are currently considered a suicide risk, any subject who has previously made a suicide attempt or who has a prior history of or are currently demonstrating active suicidal ideation. Subject has any clinically significant electrocardiogram (ECG) or clinically significant laboratory abnormality (including a positive urine drug screen) at Screening. Subject has a concurrent chronic or acute illness, disability, or other condition that might confound the results of safety assessments administered in the study or that might increase risk to the subject. Similarly, the subject will be excluded if he or she has any additional condition(s) that in the Investigator's opinion would prohibit the subject from completing the study or would not be in the best interest of the subject. This would include any significant illness or unstable medical condition that could lead to difficulty complying with the protocol. Subjects who are pregnant or who are nursing Subjects who do not agree to use adequate and reliable contraception throughout the study. Subject previously completed, discontinued or was withdrawn from this study. Subject has taken an investigational drug or taken part in a clinical trial within 30 days prior to Screening. Subjects with liver disease or reduced liver function Subjects with obstructive uropathies Subjects who consume alcohol in amounts viewed by the Investigator to be contraindicated Subjects with uncontrolled narrow angle glaucoma Subjects with seizure disorders Subjects with bleeding disorders or use of other medications that may cause bleeding

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: milnacipran<br>Milnacipran, flexibly dosed | Drug: Milnacipran<br> <br> * Other names: Savella;|
| Placebo Comparator: Sugar pill (placebo)<br>Placebo | Drug: Placebo<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Analogue Scale Score Referring to Radicular Pain (VAS-rad) | The primary outcome is change in pain VAS from baseline through 10 weeks. The effect size was calculated using the VAS scores measured on a scale of 0 to 100 mm with 0 being absence of pain or no pain noted and 100 being worst imaginable pain/as bad as can be. The higher the score the greater the over all pain intensity. Mean cumulative total scores were reported. | baseline and 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| VAS Related to Nociceptive Pain Component (VAS-Noc) | The secondary outcome is change in pain VAS from baseline through 1o weeks as related to nociceptive pain component. The effect size was calculated using the VAS scores measured on a scale of 0 to 100 mm with 0 being absence of pain or no pain noted and 100 being worst imaginable pain/as bad as can be. The higher the score the greater the over all pain intensity. Mean cumulative scores were reported | baseline and 10 weeks | 
| SF-36 (Short Form) | Self-report of quality of life. Subjective measure of perceived quality of life.The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Scoring: Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. Higher scores reflect higher quality of life with 100 high life quality. Total mean cumulative scores were reported The eight sections are: vitality physical functioning bodily pain general health perceptions physical role functioning emotional role functioning social role functioning mental health | baseline and 10 weeks | 
| Oswestry Low Back Pain Disability Questionnaire | Self report evaluation of various back pain symptoms. For each of 10 sections participants rate pain on a scale of 0-5 in these categories: Section 1 - Pain intensity Section 2 - Personal care Section 3 - Lifting Section 4 - Walking Section 5 - Sitting Section 6 - Standing Section 7 - Sleeping Section 8 - Sex life (if applicable) Section 9 - Social life Section 10 - Travelling The scores are combined form each category into overall score. Scores are converted to percentages as follows: 0% to 20%: minimal disability: The patient can cope with most living activities. 21%-40%: moderate disability: The patient experiences more pain and difficulty with sitting, lifting and standing. 41%-60%: severe disability: Pain remains the main problem-activities of daily living are affected. 61%-80%: crippled: Back pain impinges on all aspects of life. 81%-100%: Patients are either bed-bound or exaggerating their symptoms | baseline and 10 weeks | 
| Neuropathic Pain Questionnaire | Self-report evaluation of nerve pain symptoms. A low total cumulative score means less pain and higher cumulative score is greater pain. Total cumulative scores range form 0 to 1000 where in 0 is absence of pain and 1000 highest pain. | baseline and 10 weeks | 
| Beck Depression Inventory (BDI-II) | Self-report evaluation of depressive symptoms.The secondary outcome measure is change in Beck Depression Inventory. The scale for this inventory is: 0-9: indicates minimal depression 10-18: indicates mild depression 19-29: indicates moderate depression 30-63: indicates severe depression. The higher the score the degree of depression. | baseline and 10 weeks | 
| State-trait Anxiety Inventory (STAI) | Self-report evaluation of anxiety symptoms.Assessment of subjective symptoms of current anxiety and chronic anxiety. There are 20 items for assessing trait anxiety and 20 for state anxiety. State anxiety items include: I am tense; I am worried and I feel calm; I feel secure. Trait anxiety items include: I worry too much over something that really doesn't matter and I am content; I am a steady person. All items are rated on a 4-point scale Scale 1= almost never 4= almost always Higher scores indicate greater anxiety. Mean cumulative scores were reported | baseline and 10 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
sciatica radiculopathy lumbar disc lumbosacral disc