Milnacipran for Lumbosacral Radicular Pain
Primary Purpose
Radicular Pain Related to Lumbosacral Disc Disease
Status
Completed
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Milnacipran
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Radicular Pain Related to Lumbosacral Disc Disease focused on measuring sciatica radiculopathy lumbar disc lumbosacral disc
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
milnacipran
Sugar pill (placebo)
Arm Description
Milnacipran, flexibly dosed
Placebo
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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
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
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
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.
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.
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
Full Information
NCT ID
NCT01777581
First Posted
November 30, 2012
Last Updated
July 14, 2014
Sponsor
Duke University
Collaborators
Forest Laboratories
1. Study Identification
Unique Protocol Identification Number
NCT01777581
Brief Title
Milnacipran for Lumbosacral Radicular Pain
Official Title
A Ten-Week, Randomized, Double-Blind, Placebo-Controlled Parallel-Group Study of Milnacipran for Radicular Pain Associated With Lumbosacral Disk Disease
Study Type
Interventional
2. Study Status
Record Verification Date
April 2014
Overall Recruitment Status
Completed
Study Start Date
March 2010 (undefined)
Primary Completion Date
October 2011 (Actual)
Study Completion Date
October 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Duke University
Collaborators
Forest Laboratories
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Radicular Pain Related to Lumbosacral Disc Disease
Keywords
sciatica radiculopathy lumbar disc lumbosacral disc
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
13 (Actual)
8. Arms, Groups, and Interventions
Arm Title
milnacipran
Arm Type
Experimental
Arm Description
Milnacipran, flexibly dosed
Arm Title
Sugar pill (placebo)
Arm Type
Placebo Comparator
Arm Description
Placebo
Intervention Type
Drug
Intervention Name(s)
Milnacipran
Other Intervention Name(s)
Savella
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Visual Analogue Scale Score Referring to Radicular Pain (VAS-rad)
Description
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.
Time Frame
baseline and 10 weeks
Secondary Outcome Measure Information:
Title
VAS Related to Nociceptive Pain Component (VAS-Noc)
Description
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
Time Frame
baseline and 10 weeks
Title
SF-36 (Short Form)
Description
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
Time Frame
baseline and 10 weeks
Title
Oswestry Low Back Pain Disability Questionnaire
Description
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
Time Frame
baseline and 10 weeks
Title
Neuropathic Pain Questionnaire
Description
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.
Time Frame
baseline and 10 weeks
Title
Beck Depression Inventory (BDI-II)
Description
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.
Time Frame
baseline and 10 weeks
Title
State-trait Anxiety Inventory (STAI)
Description
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
Time Frame
baseline and 10 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
12. IPD Sharing Statement
Citations:
PubMed Identifier
25664215
Citation
Marks DM, Pae CU, Patkar AA. A double-blind, placebo-controlled, parallel-group pilot study of milnacipran for chronic radicular pain (sciatica) associated with lumbosacral disc disease. Prim Care Companion CNS Disord. 2014 Aug 14;16(4):10.4088/PCC.14m01658. doi: 10.4088/PCC.14m01658. eCollection 2014.
Results Reference
derived
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Milnacipran for Lumbosacral Radicular Pain
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