Trial Outcomes & Findings for Study Evaluated the Effectiveness of Milnacipran to Reduce Pain Levels in Individuals With Chronic Migraine (NCT NCT01393522)

NCT ID: NCT01393522

Last Updated: 2022-08-12

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 37 participants
• Primary outcome timeframe: Baseline and 90 days
• Results posted on: 2022-08-12

Participant Flow

Patients were recruited from two Headache focused ambulatory clinics. From Q2, 2011 until Q2, 2013. Recruitment involved printed flyers placed in the examination rooms of both sites as well as clinical staff informing patients about the study opportunity.

Patients completed a 30 day run-in period prior to randomization to ensure that they were accurate and compliant in completing diaries and experiencing sufficient headaches. Specifically they were required to have > 15 headache days and 8 (probable) migraine days . Patients below this threshold but met other headache criteria could be eligible.

Participant milestones

Measure	Milnacipran Milnacipran: titration schedule starting with 12.5mg per day increasing to 50mg twice a day, starting with day 1 to day 90 and then will taper down.	Placebo Placebo: Tablet will be titrated 1 tablet once a day increased per protocol to 2 tablets twice a day, with a starting dose of 12.5mg per day to 50 mg twice a day
Overall Study STARTED	19	18
Overall Study COMPLETED	12	14
Overall Study NOT COMPLETED	7	4

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Milnacipran n=19 Participants Milnacipran: titration schedule starting with 12.5mg per day increasing to 50mg twice a day, starting with day 1 to day 90 and then will taper down.	Placebo n=18 Participants Placebo: Tablet will be titrated 1 tablet once a day increased per protocol to 2 tablets twice a day, with a starting dose of 12.5mg per day to 50 mg twice a day	Total n=37 Participants Total of all reporting groups
Age, Continuous	38.63 years STANDARD_DEVIATION 9.59 • n=5 Participants	37.39 years STANDARD_DEVIATION 15.07 • n=7 Participants	38.01 years STANDARD_DEVIATION 12.33 • n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants	16 Participants n=7 Participants	33 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian_Non Hispanic	17 participants n=5 Participants	15 participants n=7 Participants	32 participants n=5 Participants
Race/Ethnicity, Customized Non_Caucasian	2 participants n=5 Participants	3 participants n=7 Participants	5 participants n=5 Participants
Region of Enrollment United States	19 participants n=5 Participants	18 participants n=7 Participants	37 participants n=5 Participants
Years with Headache	20.44 years STANDARD_DEVIATION 13.51 • n=5 Participants	17.89 years STANDARD_DEVIATION 9.69 • n=7 Participants	19.20 years STANDARD_DEVIATION 11.65 • n=5 Participants
Pain Severity	57.67 units on a scale STANDARD_DEVIATION 11.60 • n=5 Participants	61.87 units on a scale STANDARD_DEVIATION 17.95 • n=7 Participants	59.71 units on a scale STANDARD_DEVIATION 14.69 • n=5 Participants
MIgraine Days Per Month	10.72 Number of Days with Migraine per Month STANDARD_DEVIATION 6.79 • n=5 Participants	11.26 Number of Days with Migraine per Month STANDARD_DEVIATION 5.35 • n=7 Participants	10.98 Number of Days with Migraine per Month STANDARD_DEVIATION 6.09 • n=5 Participants
MSQ- Preventive	53.89 Standard Score STANDARD_DEVIATION 21.04 • n=5 Participants	47.78 Standard Score STANDARD_DEVIATION 22.83 • n=7 Participants	50.92 Standard Score STANDARD_DEVIATION 21.91 • n=5 Participants
MSQ- Restrictive	37.78 Standard Score STANDARD_DEVIATION 13.63 • n=5 Participants	33.68 Standard Score STANDARD_DEVIATION 18.58 • n=7 Participants	35.79 Standard Score STANDARD_DEVIATION 16.04 • n=5 Participants
MSQ-Emotional	38.15 Standard Score STANDARD_DEVIATION 20.43 • n=5 Participants	30.53 Standard Score STANDARD_DEVIATION 26.14 • n=7 Participants	34.44 Standard Score STANDARD_DEVIATION 23.21 • n=5 Participants
PHQ-9	3.78 units on a scale STANDARD_DEVIATION 3.12 • n=5 Participants	5.05 units on a scale STANDARD_DEVIATION 4.18 • n=7 Participants	4.40 units on a scale STANDARD_DEVIATION 3.64 • n=5 Participants
GAD-7	2.89 units on a scale STANDARD_DEVIATION 3.63 • n=5 Participants	3.74 units on a scale STANDARD_DEVIATION 3.94 • n=7 Participants	3.30 units on a scale STANDARD_DEVIATION 3.78 • n=5 Participants
BMI	29.67 kg/m^2 STANDARD_DEVIATION 7.62 • n=5 Participants	28.32 kg/m^2 STANDARD_DEVIATION 5.93 • n=7 Participants	29.01 kg/m^2 STANDARD_DEVIATION 6.80 • n=5 Participants
Blood Pressure - Systolic	120.83 mmHg STANDARD_DEVIATION 13.43 • n=5 Participants	114.47 mmHg STANDARD_DEVIATION 13.34 • n=7 Participants	117.74 mmHg STANDARD_DEVIATION 13.39 • n=5 Participants
Blood Pressure - Diastolic	74.67 mmHg STANDARD_DEVIATION 11.66 • n=5 Participants	76.83 mmHg STANDARD_DEVIATION 8.84 • n=7 Participants	75.72 mmHg STANDARD_DEVIATION 10.29 • n=5 Participants
Pulse	74.44 Beats Per Minute STANDARD_DEVIATION 8.26 • n=5 Participants	75.47 Beats Per Minute STANDARD_DEVIATION 9.62 • n=7 Participants	74.94 Beats Per Minute STANDARD_DEVIATION 10.61 • n=5 Participants
Non-Migraine Headache Days	11.41 Days w/ Non-Migraine Headache per Month STANDARD_DEVIATION 8.02 • n=5 Participants	10.65 Days w/ Non-Migraine Headache per Month STANDARD_DEVIATION 5.80 • n=7 Participants	11.04 Days w/ Non-Migraine Headache per Month STANDARD_DEVIATION 6.94 • n=5 Participants
Days Using Medication for Headache Per Month	15.59 Days per Month STANDARD_DEVIATION 3.22 • n=5 Participants	14.63 Days per Month STANDARD_DEVIATION 7.22 • n=7 Participants	15.12 Days per Month STANDARD_DEVIATION 5.17 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 90 days

Population: Intent to treat population (all participants who were randomized to one of the conditions and treated at least one migraine with Milnacipran or Placebo).

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.

Outcome measures

Measure	Milnacipran n=19 Participants Milnacipran: titration schedule starting with 12.5mg per day increasing to 50mg twice a day, starting with day 1 to day 90 and then will taper down.	Placebo n=18 Participants Placebo: Tablet will be titrated 1 tablet once a day increased per protocol to 2 tablets twice a day, with a starting dose of 12.5mg per day to 50 mg twice a day
Change in VAS Pain Severity	3.23 units on a scale Interval 2.1 to 4.37	5.36 units on a scale Interval 4.25 to 6.45

PRIMARY outcome

Timeframe: Baseline and 90 days

Population: Intent to treat population (all participants who were randomized to one of the conditions and treated at least one migraine with Milnacipran or Placebo).

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.

Outcome measures

Measure	Milnacipran n=19 Participants Milnacipran: titration schedule starting with 12.5mg per day increasing to 50mg twice a day, starting with day 1 to day 90 and then will taper down.	Placebo n=18 Participants Placebo: Tablet will be titrated 1 tablet once a day increased per protocol to 2 tablets twice a day, with a starting dose of 12.5mg per day to 50 mg twice a day
Change in Migraine Specific Quality of Life - Restrictive	21.01 units on a scale Interval 17.31 to 24.72	35.03 units on a scale Interval 31.43 to 38.62

PRIMARY outcome

Timeframe: Baseline and 90 days

Population: Intent to treat population (all participants who were randomized to one of the conditions and treated at least one migraine with Milnacipran or Placebo).

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.

Outcome measures

Measure	Milnacipran n=19 Participants Milnacipran: titration schedule starting with 12.5mg per day increasing to 50mg twice a day, starting with day 1 to day 90 and then will taper down.	Placebo n=18 Participants Placebo: Tablet will be titrated 1 tablet once a day increased per protocol to 2 tablets twice a day, with a starting dose of 12.5mg per day to 50 mg twice a day
Change in Migraine Specific Quality of Life - Preventive	21.61 units on a scale Interval 21.46 to 21.77	31.26 units on a scale Interval 31.1 to 31.42

PRIMARY outcome

Timeframe: Baseline and 90 days

Population: Intent to treat population (all participants who were randomized to one of the conditions and treated at least one migraine with Milnacipran or Placebo).

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.

Outcome measures

Measure	Milnacipran n=19 Participants Milnacipran: titration schedule starting with 12.5mg per day increasing to 50mg twice a day, starting with day 1 to day 90 and then will taper down.	Placebo n=18 Participants Placebo: Tablet will be titrated 1 tablet once a day increased per protocol to 2 tablets twice a day, with a starting dose of 12.5mg per day to 50 mg twice a day
Change in Migraine Specific Quality of Life - Emotional	29.89 units on a scale Interval 28.68 to 31.12	37.99 units on a scale Interval 36.81 to 39.18

SECONDARY outcome

Timeframe: Baseline and 90 days

Population: Intent to treat population (all participants who were randomized to one of the conditions and treated at least one migraine with Milnacipran or Placebo).

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]

Outcome measures

Measure	Milnacipran n=19 Participants Milnacipran: titration schedule starting with 12.5mg per day increasing to 50mg twice a day, starting with day 1 to day 90 and then will taper down.	Placebo n=18 Participants Placebo: Tablet will be titrated 1 tablet once a day increased per protocol to 2 tablets twice a day, with a starting dose of 12.5mg per day to 50 mg twice a day
Change in Days With Migraine Per Month From Baseline to 90 Days	3.34 Days per Month Interval 3.13 to 3.54	4.62 Days per Month Interval 4.42 to 4.84

SECONDARY outcome

Timeframe: Baseline and 90 days

Population: Intent to treat population (all participants who were randomized to one of the conditions and treated at least one migraine with Milnacipran or Placebo).

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]

Outcome measures

Measure	Milnacipran n=19 Participants Milnacipran: titration schedule starting with 12.5mg per day increasing to 50mg twice a day, starting with day 1 to day 90 and then will taper down.	Placebo n=18 Participants Placebo: Tablet will be titrated 1 tablet once a day increased per protocol to 2 tablets twice a day, with a starting dose of 12.5mg per day to 50 mg twice a day
Change in Days With Non-Migraine Headache Per Month From Baseline to 90 Days	2.35 Days per Month Interval 1.81 to 2.89	0.76 Days per Month Interval 0.22 to 1.31

SECONDARY outcome

Timeframe: Baseline and 90 days

Population: Intent to treat population (all participants who were randomized to one of the conditions and treated at least one migraine with Milnacipran or Placebo).

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]

Outcome measures

Measure	Milnacipran n=19 Participants Milnacipran: titration schedule starting with 12.5mg per day increasing to 50mg twice a day, starting with day 1 to day 90 and then will taper down.	Placebo n=18 Participants Placebo: Tablet will be titrated 1 tablet once a day increased per protocol to 2 tablets twice a day, with a starting dose of 12.5mg per day to 50 mg twice a day
Change in Days Using Headache Medication Per Month From Baseline to 90 Days	1.28 Days per Month Interval -0.17 to 2.75	2.17 Days per Month Interval 0.79 to 3.54

Adverse Events

Milnacipran

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Milnacipran n=19 participants at risk Milnacipran: titration schedule starting with 12.5mg per day increasing to 50mg twice a day, starting with day 1 to day 90 and then will taper down.	Placebo n=18 participants at risk Placebo: Tablet will be titrated 1 tablet once a day increased per protocol to 2 tablets twice a day, with a starting dose of 12.5mg per day to 50 mg twice a day
Gastrointestinal disorders nausea	10.5% 2/19 • Number of events 2	5.6% 1/18 • Number of events 1
Psychiatric disorders anxiety	5.3% 1/19 • Number of events 1	0.00% 0/18
Ear and labyrinth disorders dizziness	5.3% 1/19 • Number of events 1	0.00% 0/18
Renal and urinary disorders testicular discomfort	5.3% 1/19 • Number of events 1	0.00% 0/18

Additional Information

Timothy R. Smith, MD

Mercy Health Research

Phone: 314-251-8895

Email: Timothy.Smith@mercy.net

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place