Study Evaluated the Effectiveness of Milnacipran to Reduce Pain Levels in Individuals With Chronic Migraine

NCT ID: NCT01393522

Last Updated: 2022-08-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-06-30
• Study Completion Date: 2013-12-31

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.

Conditions

Chronic Migraine

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Milnacipran

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.

Group Type: ACTIVE_COMPARATOR

Milnacipran

Intervention Type: DRUG

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.

Placebo

Sugar Pill No active ingredients

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

Milnacipran

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

Placebo

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

Intervention Type: DRUG

Other Intervention Names

Savella; Sugar Pill

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Timothy Smith

OTHER

Sponsor Role: lead

Responsible Party

Timothy Smith

Vice President of Clinical Research

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Timothy Smith, MD

Role: PRINCIPAL_INVESTIGATOR

Mercy Research

Locations

Mercy Health Research

St Louis, Missouri, United States

Headache Wellness Center

Greensboro, North Carolina, United States

Countries

United States

Other Identifiers

SAV-MD-25

Identifier Type: -

Identifier Source: org_study_id