Milnacipran for Lumbosacral Radicular Pain

Phase 4

Completed

• Conditions: Radicular Pain Related to Lumbosacral Disc Disease
• Interventions: Drug: Placebo; Drug: Milnacipran

• Registration Number: NCT01777581
• Lead Sponsor: Duke University

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.

Study Timeline

• Study Start: 2010-03
• Primary Completion: 2011-10
• Study Completion: 2011-10
• Study First Submitted: 2012-11-30
• Study First Submitted QC: 2013-01-24
• Study First Posted: 2013-01-29
• Results First Submitted: 2013-09-20
• Status Verified: 2014-04
• Results First Submitted QC: 2014-04-29
• Results First Posted: 2014-05-23
• Last Update Submitted: 2014-07-14
• Last Update Posted: 2014-07-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13

Inclusion Criteria

1. Subject is a male or female adult outpatient age 18 or older at the time of consent.
2. 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.
3. Subject-rated VAS specifically related to radicular pain > or = 40 mm at screen and baseline visits
4. Subject has an understanding, ability and willingness to fully comply with study procedures and restrictions.
5. 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

1. Subjects unable to complete assessments due to language or cognitive impairment
2. Subjects treated with antidepressant or anticonvulsant medication within 4 weeks of screening visit (6 weeks for fluoxetine).
3. Subjects taking monoamine oxidase inhibitors
4. Subjects who have received procedural intervention within 3 months of screen.
5. Subjects with known sensitivity to milnacipran.
6. Subjects unable to complete the questionnaires due to language or cognitive impairment.
7. Subjects with a history of bipolar disorder or psychosis as confirmed by the Mini International Neuropsychiatric Interview (MINI).
8. 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).
9. 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.
10. Subject has any clinically significant electrocardiogram (ECG) or clinically significant laboratory abnormality (including a positive urine drug screen) at Screening.
11. 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.
12. Subjects who are pregnant or who are nursing
13. Subjects who do not agree to use adequate and reliable contraception throughout the study.
14. Subject previously completed, discontinued or was withdrawn from this study.
15. Subject has taken an investigational drug or taken part in a clinical trial within 30 days prior to Screening.
16. Subjects with liver disease or reduced liver function
17. Subjects with obstructive uropathies
18. Subjects who consume alcohol in amounts viewed by the Investigator to be contraindicated
19. Subjects with uncontrolled narrow angle glaucoma
20. Subjects with seizure disorders
21. Subjects with bleeding disorders or use of other medications that may cause bleeding

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sugar pill (placebo)	Placebo	Placebo
milnacipran	Milnacipran	Milnacipran, flexibly dosed

Primary Outcome Measures

Name	Time	Method
Visual Analogue Scale Score Referring to Radicular Pain (VAS-rad)	baseline and 10 weeks	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.

Secondary Outcome Measures

Name	Time	Method
VAS Related to Nociceptive Pain Component (VAS-Noc)	baseline and 10 weeks	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
SF-36 (Short Form)	baseline and 10 weeks	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
Oswestry Low Back Pain Disability Questionnaire	baseline and 10 weeks	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
Neuropathic Pain Questionnaire	baseline and 10 weeks	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.
Beck Depression Inventory (BDI-II)	baseline and 10 weeks	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.
State-trait Anxiety Inventory (STAI)	baseline and 10 weeks	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