Back to resultsStudy Evaluated the Effectiveness of Milnacipran to Reduce Pain Levels in Individuals With Chronic Migraine
Primary Purpose
Chronic Migraine
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Milnacipran
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Chronic Migraine focused on measuring headache, migraine
Eligibility Criteria
Inclusion Criteria:
- Individuals between the age of 18 and 65
- Headache fulfills ICHD-2 criteria for: chronic migraine, or probable medication overuse headache where individual headaches meet criteria for migraine
- At least 15 headache days/month and at least 8 migraine or probable migraine days/month for the past 3 months, by patient report (including days of headache relieved with a triptan or related compound).
- Age at onset of chronic migraine < 60 years old
Exclusion Criteria:
- Pregnancy or attempting conception
- Unable to read or write English
- Use of Opiates >/= 10 days per month
- Subject has failed >/= 4 adequate preventive trials of antidepressant medications due to lack of efficacy; at least one trial included another SNRI.(An adequate preventive trial defined as at least 6 weeks on therapeutic dose [150mg of amitriptyline or nortriptyline or other tricyclic, 150mg of venlafaxine, 60mg of duloxetine])
- Subjects on antidepressant medications, including SNRIs who cannot safely withdraw from those medications, in the assessment of the PI. Subjects on other headache preventives (beta blockers, antiepileptic drugs), at stable dose for at least three months, will be allowed to participate.
A. Subjects on other headache preventives may be included in the study if the medication has been at a stable dose for 3 months.
- Presence of fibromyalgia or another pain or medical disorder that would make it difficult for patient to distinguish headache-related quality of life from overall health related quality of life.
- Uncontrolled or unstable psychiatric disorder (PHQ-9 score or GAD-7 score >15 with sentinel questions >/=4, or in opinion of examiner), or anticipated need for change in psychotropic medications during duration of study period; or suicidality.
- Chronic kidney disease, liver disease, or any poorly controlled medical condition
Sites / Locations
- Mercy Health Research
- Headache Wellness Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Milnacipran
Placebo
Arm Description
Oral Milnacipran titration was Day 1-2 - 12.5mg/d; Day 3-6 - 12.5mg bid; Day 7-14 - 25mg bid; Day 15 and on - 50mg bid. After the first 30 days, patients did not continue to increase the dose beyond the dose they have achieved at 30 days. At study completion medication taper as follows: patients who at their completion visit were taking 50mg bid decreased to 25mg bid for 4 days, then decreased to 12.5mg bid for 2 days, then 12.5mg once a day for one day and then stopped. Patients on 25mg bid, decreased to 12.5mg bid for 2 days, 12.5mg once a day for one day and then stopped.
Sugar Pill No active ingredients
Outcomes
Primary Outcome Measures
Change in VAS Pain Severity
On headache days, patients were instructed to complete a Visual Analog Scale (VAS) to rate their pain intensity. Their response (the scale was 100 cm long) was measured and assigned a score (0-100) with higher numbers indicating more severity. Scores were averaged over a 30 day period to create the score for a time period (baseline and 90 days). Change in Pain score = Score[Baseline] - Score[90 days]. Higher scores indicate greater pain reduction.
Change in Migraine Specific Quality of Life - Restrictive
The Migraine Specific Quality of Life measures the impact Migraine has on the patient's Quality of Life. The Restrictive subscale assesses the extent to which migraine restricts the patient's function. The subscale is measured on a standard scale from 0-100, where higher scores indicate better quality of life. For the outcome assessing change, higher positive scores indicate better outcomes.
Change in Migraine Specific Quality of Life - Preventive
The Migraine Specific Quality of Life measures the impact Migraine has on the patient's Quality of Life. The Preventive subscale assesses the extent to which migraine prevents the patient's function. The subscale is measured on a standard scale from 0-100, where higher scores indicate better quality of life. For the outcome assessing change, higher positive scores indicate better outcomes.
Change in Migraine Specific Quality of Life - Emotional
The Migraine Specific Quality of Life measures the impact Migraine has on the patient's Quality of Life. The Emotional subscale assesses the extent to which migraine influences the patient's emotional function. The subscale is measured on a standard scale from 0-100, where higher scores indicate better quality of life. For the outcome assessing change, higher positive scores indicate better outcomes.
Secondary Outcome Measures
Change in Days With Migraine Per Month From Baseline to 90 Days
On days where the patient indicated they had a headache, patients were instructed to complete the diary questions regarding headache characteristics using International Headache Classification Diagnostics. This information was used to calculate migraine days per month. Days with migraine over a 30 day period were summed to generate a number for each time frame (baseline and 90 days). For the outcome measure, higher positive numbers indicate higher reduction of days with migraine.
Change in days with migraine = Score[Baseline] - Score[90days]
Change in Days With Non-Migraine Headache Per Month From Baseline to 90 Days
On days where the patient indicated they had a headache, patients were instructed to complete the diary questions regarding headache characteristics using International Headache Classification Diagnostics. This was information was used to calculate non-migraine headache days days per month. Days with migraine over a 30 day period were summed to generate a number for each time frame (baseline and 90 days). For the outcome measure, higher positive numbers indicate higher reduction of days with non-migraine headache.
Change in days with non-migraine headache = Score[Baseline] - Score[90 days]
Change in Days Using Headache Medication Per Month From Baseline to 90 Days
On days where the patient indicated they had a headache (i.e., migraine or non-migraine headache), patients were instructed to complete the diary questions regarding whether they used medication to treat headache pain and related symptoms. This was used to calculate days using headache medication days per month. Days with migraine over a 30 day period were summed to generate a number for each time frame (baseline and 90 days). For the outcome measure, higher positive numbers indicate higher reduction of days using headache medication per month.
Change in days using headache medication = Score[Baseline] - Score[90 days]
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01393522
Brief Title
Study Evaluated the Effectiveness of Milnacipran to Reduce Pain Levels in Individuals With Chronic Migraine
Official Title
A Randomized Double Blind Placebo Control Trial of Milnacipran for Migraine Pain
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
June 2011 (undefined)
Primary Completion Date
December 2013 (Actual)
Study Completion Date
December 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Timothy Smith
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to determine if milnacipran taken twice daily is effective in reduction of headache pain.
Detailed Description
Milnacipran is a serotonin norepinephrine reubtake inhibitor (SNRI) approved for the management of fibromyalgia in the United States.
Migraine and fibromyalgia have significant co-morbidity. Of 100 patients with fibromyalgia, 76% had chronic headaches, of whom 63% had migraine. Interestingly, general measures of pain, disability, sleep quality, and psychological distress were similar in individuals with fibromyalgia with and without headache. Conversely, the prevalence of fibromyalgia in women with migraine was reported as 22%, and at a headache referral center, 36% of headache patients had fibromyalgia.
Because of significant co-morbidity, as well as the likelihood of shared pathophysiologic mechanisms, there is reason to believe that a medication effective for fibromyalgia might reduce migraine pain, especially where the pain has taken on the nature of a chronic pain disorder, as in chronic migraine. The current study evaluated the benefits of milnacipran in individuals with chronic migraine.
Patients with chronic migraine were randomized to either Milnacipran or Placebo. Patients completed 30 days of baseline followed by 90 days of headache diaries while taking assigned medication. Primary outcomes were reduction in pain severity and improvement in migraine specific quality of life (MSQ) while secondary outcomes included reduction in migraine and non-migraine headache days and symptomatic use of medication for migraine. Independent sample t-tests were used to evaluate the changes in primary and secondary measures between the two groups.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Migraine
Keywords
headache, migraine
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
37 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Milnacipran
Arm Type
Active Comparator
Arm Description
Oral Milnacipran titration was Day 1-2 - 12.5mg/d; Day 3-6 - 12.5mg bid; Day 7-14 - 25mg bid; Day 15 and on - 50mg bid. After the first 30 days, patients did not continue to increase the dose beyond the dose they have achieved at 30 days. At study completion medication taper as follows: patients who at their completion visit were taking 50mg bid decreased to 25mg bid for 4 days, then decreased to 12.5mg bid for 2 days, then 12.5mg once a day for one day and then stopped. Patients on 25mg bid, decreased to 12.5mg bid for 2 days, 12.5mg once a day for one day and then stopped.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Sugar Pill No active ingredients
Intervention Type
Drug
Intervention Name(s)
Milnacipran
Other Intervention Name(s)
Savella
Intervention Description
titration schedule starting with 12.5mg per day increasing to 50mg twice a day, starting with day 1 to day 90 and then taper down as appropriate for dose.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Sugar Pill
Intervention Description
Placebo dosing schedule was Day 1-2, 1 tablet daily, Day 3-6 BID, Day 7-14 BID, Day 15 an on through day 90 BID and taper down
Primary Outcome Measure Information:
Title
Change in VAS Pain Severity
Description
On headache days, patients were instructed to complete a Visual Analog Scale (VAS) to rate their pain intensity. Their response (the scale was 100 cm long) was measured and assigned a score (0-100) with higher numbers indicating more severity. Scores were averaged over a 30 day period to create the score for a time period (baseline and 90 days). Change in Pain score = Score[Baseline] - Score[90 days]. Higher scores indicate greater pain reduction.
Time Frame
Baseline and 90 days
Title
Change in Migraine Specific Quality of Life - Restrictive
Description
The Migraine Specific Quality of Life measures the impact Migraine has on the patient's Quality of Life. The Restrictive subscale assesses the extent to which migraine restricts the patient's function. The subscale is measured on a standard scale from 0-100, where higher scores indicate better quality of life. For the outcome assessing change, higher positive scores indicate better outcomes.
Time Frame
Baseline and 90 days
Title
Change in Migraine Specific Quality of Life - Preventive
Description
The Migraine Specific Quality of Life measures the impact Migraine has on the patient's Quality of Life. The Preventive subscale assesses the extent to which migraine prevents the patient's function. The subscale is measured on a standard scale from 0-100, where higher scores indicate better quality of life. For the outcome assessing change, higher positive scores indicate better outcomes.
Time Frame
Baseline and 90 days
Title
Change in Migraine Specific Quality of Life - Emotional
Description
The Migraine Specific Quality of Life measures the impact Migraine has on the patient's Quality of Life. The Emotional subscale assesses the extent to which migraine influences the patient's emotional function. The subscale is measured on a standard scale from 0-100, where higher scores indicate better quality of life. For the outcome assessing change, higher positive scores indicate better outcomes.
Time Frame
Baseline and 90 days
Secondary Outcome Measure Information:
Title
Change in Days With Migraine Per Month From Baseline to 90 Days
Description
On days where the patient indicated they had a headache, patients were instructed to complete the diary questions regarding headache characteristics using International Headache Classification Diagnostics. This information was used to calculate migraine days per month. Days with migraine over a 30 day period were summed to generate a number for each time frame (baseline and 90 days). For the outcome measure, higher positive numbers indicate higher reduction of days with migraine.
Change in days with migraine = Score[Baseline] - Score[90days]
Time Frame
Baseline and 90 days
Title
Change in Days With Non-Migraine Headache Per Month From Baseline to 90 Days
Description
On days where the patient indicated they had a headache, patients were instructed to complete the diary questions regarding headache characteristics using International Headache Classification Diagnostics. This was information was used to calculate non-migraine headache days days per month. Days with migraine over a 30 day period were summed to generate a number for each time frame (baseline and 90 days). For the outcome measure, higher positive numbers indicate higher reduction of days with non-migraine headache.
Change in days with non-migraine headache = Score[Baseline] - Score[90 days]
Time Frame
Baseline and 90 days
Title
Change in Days Using Headache Medication Per Month From Baseline to 90 Days
Description
On days where the patient indicated they had a headache (i.e., migraine or non-migraine headache), patients were instructed to complete the diary questions regarding whether they used medication to treat headache pain and related symptoms. This was used to calculate days using headache medication days per month. Days with migraine over a 30 day period were summed to generate a number for each time frame (baseline and 90 days). For the outcome measure, higher positive numbers indicate higher reduction of days using headache medication per month.
Change in days using headache medication = Score[Baseline] - Score[90 days]
Time Frame
Baseline and 90 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Individuals between the age of 18 and 65
Headache fulfills ICHD-2 criteria for: chronic migraine, or probable medication overuse headache where individual headaches meet criteria for migraine
At least 15 headache days/month and at least 8 migraine or probable migraine days/month for the past 3 months, by patient report (including days of headache relieved with a triptan or related compound).
Age at onset of chronic migraine < 60 years old
Exclusion Criteria:
Pregnancy or attempting conception
Unable to read or write English
Use of Opiates >/= 10 days per month
Subject has failed >/= 4 adequate preventive trials of antidepressant medications due to lack of efficacy; at least one trial included another SNRI.(An adequate preventive trial defined as at least 6 weeks on therapeutic dose [150mg of amitriptyline or nortriptyline or other tricyclic, 150mg of venlafaxine, 60mg of duloxetine])
Subjects on antidepressant medications, including SNRIs who cannot safely withdraw from those medications, in the assessment of the PI. Subjects on other headache preventives (beta blockers, antiepileptic drugs), at stable dose for at least three months, will be allowed to participate.
A. Subjects on other headache preventives may be included in the study if the medication has been at a stable dose for 3 months.
Presence of fibromyalgia or another pain or medical disorder that would make it difficult for patient to distinguish headache-related quality of life from overall health related quality of life.
Uncontrolled or unstable psychiatric disorder (PHQ-9 score or GAD-7 score >15 with sentinel questions >/=4, or in opinion of examiner), or anticipated need for change in psychotropic medications during duration of study period; or suicidality.
Chronic kidney disease, liver disease, or any poorly controlled medical condition
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Timothy Smith, MD
Organizational Affiliation
Mercy Research
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mercy Health Research
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63141
Country
United States
Facility Name
Headache Wellness Center
City
Greensboro
State/Province
North Carolina
ZIP/Postal Code
27405
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Study Evaluated the Effectiveness of Milnacipran to Reduce Pain Levels in Individuals With Chronic Migraine
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