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Drug and Non-Drug Treatment Of Severe Migraine (TSM)

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ClinicalTrials.gov Identifier: NCT00910689
Recruitment Status : Completed
First Posted : June 1, 2009
Results First Posted : June 1, 2009
Last Update Posted : November 22, 2016
Sponsor:
Collaborators:
National Institute of Neurological Disorders and Stroke (NINDS)
Merck Sharp & Dohme Corp.
GlaxoSmithKline
Information provided by:
Ohio University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Migraine Headache
Interventions Drug: Propranolol or nadolol
Drug: Placebo control
Behavioral: Behavioral Migraine Management (BMM)
Drug: Optimal Acute Therapy
Enrollment 232
Recruitment Details Outpatient clinics
Pre-assignment Details 5 week Optimal Acute Therapy (OAT) Run in (M1) precedes random assignment (see detailed design description).
Arm/Group Title OAT + Placebo (PL) OAT + Beta Blocker (Beta-B) OAT + BMM + PL OAT + BMM + Beta-B
Hide Arm/Group Description Optimal Acute Therapy plus Beta Blocker Placebo Optimal Acute Therapy plus Beta Blocker (propranolol or nadolol) Optimal Acute Therapy plus Behavioral Migraine Management plus placebo Optimal Acute Therapy plus Behavioral Migraine Management plus Beta Blocker (propranolol or nadolol)
Period Title: Month 1: Optimal Acute Therapy Run in
Started 55 53 55 69
Completed 53 52 50 59
Not Completed 2 1 5 10
Reason Not Completed
No Post OAT Run-in data             2             1             5             10
Period Title: Month 2- 4: Treatment Period
Started 53 52 50 59
Completed 44 42 42 48
Not Completed 9 10 8 11
Reason Not Completed
Lost to Follow-up             3             4             1             3
Adverse Event             2             3             2             0
Time Demands             1             0             4             8
Lack of Efficacy             2             1             0             0
Perceived Improvement             0             0             1             0
Pregnancy             0             2             0             0
Protocol Violation             1             0             0             0
Period Title: Months 5 - 10: Evaluation Period I
Started 44 42 42 48
Completed 40 35 35 41
Not Completed 4 7 7 7
Reason Not Completed
Lost to Follow-up             2             5             1             1
Adverse Event             1             0             2             4
Lack of Efficacy             0             1             1             1
Protocol Violation             1             1             0             0
Pregnancy             0             0             2             0
Time Demands             0             0             1             1
Period Title: Months 11- 16: Evaluation Period II
Started 40 35 35 41
Completed 30 25 28 35
Not Completed 10 10 7 6
Reason Not Completed
Lost to Follow-up             3             0             1             2
Adverse Event             2             4             2             2
Pregnancy             1             0             0             0
Lack of Efficacy             2             3             3             1
Time Demands             2             1             0             0
Perceived Improvement             0             0             0             1
Physician Decision             0             2             1             0
Arm/Group Title OAT + Placebo (PL) OAT + Beta Blocker (Beta-B) OAT + BMM + PL OAT + BMM + Beta-B Total
Hide Arm/Group Description Optimal Acute Therapy plus Beta Blocker Placebo Optimal Acute Therapy plus Beta Blocker (propranolol or nadolol) Optimal Acute Therapy plus Behavioral Migraine Management plus placebo Optimal Acute Therapy plus Behavioral Migraine Management plus Beta Blocker (propranolol or nadolol) Total of all reporting groups
Overall Number of Baseline Participants 55 53 55 69 232
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 55 participants 53 participants 55 participants 69 participants 232 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
55
 100.0%
53
 100.0%
55
 100.0%
69
 100.0%
232
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 55 participants 53 participants 55 participants 69 participants 232 participants
39.5  (10.2) 37.7  (10.1) 37.1  (9.4) 38.3  (10.9) 38.2  (10.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 55 participants 53 participants 55 participants 69 participants 232 participants
Female
45
  81.8%
45
  84.9%
45
  81.8%
49
  71.0%
184
  79.3%
Male
10
  18.2%
8
  15.1%
10
  18.2%
20
  29.0%
48
  20.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 55 participants 53 participants 55 participants 69 participants 232 participants
55 53 55 69 232
1.Primary Outcome
Title Change in Number of Migraine Episodes Per 30 Days at Month 10.
Hide Description Change in number of migraine episodes(with 24 hours pain free period required between episodes)per 30 days from OAT run-in (Month 1) to Month 10.Obtained from daily electronic diary.
Time Frame Change from Month 1 to Month 10
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy analyses were intent-to-treat analyses that included all randomized (N = 232) participants.
Arm/Group Title OAT + Placebo (PL) OAT + Beta Blocker (Beta-B) OAT + BMM + PL OAT + BMM + Beta-B
Hide Arm/Group Description:
Optimal Acute Therapy plus Beta Blocker Placebo
Optimal Acute Therapy plus Beta Blocker (propranolol or nadolol)
Optimal Acute Therapy plus Behavioral Migraine Management plus placebo
Optimal Acute Therapy plus Behavioral Migraine Management plus Beta Blocker (propranolol or nadolol)
Overall Number of Participants Analyzed 55 53 55 69
Mean (95% Confidence Interval)
Unit of Measure: Number of Migraine episodes
-2.1
(-2.2 to -1.9)
-2.1
(-2.2 to -1.9)
-2.2
(-2.4 to -2.0)
-3.3
(-3.5 to -3.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OAT + Placebo (PL), OAT + Beta Blocker (Beta-B), OAT + BMM + PL, OAT + BMM + Beta-B
Comments Omnibus Test: A mixed model with fixed effects for treatment,natural time(defined as natural log of months) and treatment-by-time interaction was used to obtain maximum likelihood estimates of missing values and to evaluate treatment effects(using the PROC MIXED procedure in SAS statistical software,version 9;www.sas.com). A significant treatment by time interaction(p < .05, 2-tailed) was followed by post-tests (see below). Details of significant post tests are reported as separate analyses.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < .01
Comments Post tests consisted of 6 pair wise contrasts: The first 3 contrasts compared each of the 3 additive treatments (Trial Arms 2, 3, 4) to OAT + PL (Trial arm 1); 3 additional contrasts compared the 3 additive treatments to one another.
Method Mixed Models Analysis
Comments A Bonferoni procedure was used to control the family-wise type I error for the 6 post test contrasts at .05. Adjusted p =.0083.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection OAT + Placebo (PL), OAT + BMM + Beta-B
Comments Post-test contrast. Mean difference in change.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < .001
Comments Bonferoni adjusted critical value p = .0083.
Method t-test, 2 sided
Comments Degrees of freedom = 1 and 122.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.2
Parameter Dispersion
Type: Standard Deviation
Value: 0.57
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection OAT + Placebo (PL), OAT + BMM + PL
Comments Post-test contrast. Mean difference in change.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value > .25
Comments Bonferoni adjusted critical value p = .0083.
Method t-test, 2 sided
Comments Degrees of freedom = 1 and 108.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.1
Parameter Dispersion
Type: Standard Deviation
Value: 0.68
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection OAT + Placebo (PL), OAT + Beta Blocker (Beta-B)
Comments Post-test contrast. Mean difference in change.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value > .98
Comments Bonferoni adjusted critical value p = .0083.
Method t-test, 2 sided
Comments Degrees of freedom = 1 and 106.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.0
Parameter Dispersion
Type: Standard Deviation
Value: 0.59
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection OAT + BMM + PL, OAT + BMM + Beta-B
Comments Post-test contrast. Mean difference in change.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < .001
Comments Bonferoni adjusted critical value p = .0083.
Method t-test, 2 sided
Comments Degrees of freedom = 1 and 122.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.1
Parameter Dispersion
Type: Standard Deviation
Value: 0.69
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection OAT + Beta Blocker (Beta-B), OAT + BMM + Beta-B
Comments Post-test contrast. Mean difference in change.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments Bonferoni adjusted critical value p = .0083.
Method t-test, 2 sided
Comments Degrees of freedom = 1 and 120.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.3
Parameter Dispersion
Type: Standard Deviation
Value: 0.61
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection OAT + Beta Blocker (Beta-B), OAT + BMM + PL
Comments Post-test contrast. Mean difference in change.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >.29
Comments Bonferoni adjusted critical value p = .0083.
Method t-test, 2 sided
Comments Degrees of freedom = 1 and 106.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.1
Parameter Dispersion
Type: Standard Deviation
Value: 0.72
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change in the Number of Migraine Days Per 30 Days at Month 10
Hide Description Change in the number of days with migraine per 30 days at Month 10 relative to the OAT Run-in (Month 1). Obtained from daily electronic diary.
Time Frame Change from Month 1 to Month 10
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy analyses were intent-to-treat analyses that included all randomized (N = 232) participants.
Arm/Group Title OAT + Placebo (PL) OAT + Beta Blocker (Beta-B) OAT + BMM + PL OAT + BMM + Beta-B
Hide Arm/Group Description:
Optimal Acute Therapy plus Beta Blocker Placebo
Optimal Acute Therapy plus Beta Blocker (propranolol or nadolol)
Optimal Acute Therapy plus Behavioral Migraine Management plus placebo
Optimal Acute Therapy plus Behavioral Migraine Management plus Beta Blocker (propranolol or nadolol)
Overall Number of Participants Analyzed 55 53 55 69
Mean (95% Confidence Interval)
Unit of Measure: Number of days
-3.3
(-3.6 to -3.0)
-3.9
(-4.2 to -3.5)
-3.3
(-3.7 to -2.9)
-5.4
(-5.6 to -5.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OAT + Placebo (PL), OAT + Beta Blocker (Beta-B), OAT + BMM + PL, OAT + BMM + Beta-B
Comments Omnibus test:A mixed model with fixed effects for treatment, time (defined as the natural log of months), and the treatment-by-time interaction was used to obtain maximum likelihood estimates of missing values and to evaluate treatment effects (PROC MIXED, SAS 9).When the treatment by time interaction was significant (p < .05, 2-tailed)post-tests were conducted (see below).Details of significant post tests are reported as separate analyses.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < .03
Comments 6 pair wise contrasts were conducted: The first 3 contrasts compared each of the 3 additive treatments to OAT + PL. The 3 additional contrasts compared the 3 additive treatments to one another.
Method Mixed Models Analysis
Comments A Bonferoni procedure was used to control the family wise type I error for the 6 post test contrasts at .05. Adjusted p =.0083.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection OAT + Placebo (PL), OAT + BMM + Beta-B
Comments Post-test contrast. Mean difference in change.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < .001
Comments Bonferoni adjusted critical value p = .0083.
Method t-test, 2 sided
Comments Degrees of freedom = 1 and 122.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.0
Parameter Dispersion
Type: Standard Deviation
Value: 1.03
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection OAT + Beta Blocker (Beta-B), OAT + BMM + Beta-B
Comments Post-test contrast. Mean difference in change.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < .001
Comments Bonferoni adjusted critical value p = .0083.
Method t-test, 2 sided
Comments Degrees of freedom = 1 and 122.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.5
Parameter Dispersion
Type: Standard Deviation
Value: 1.12
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection OAT + BMM + PL, OAT + BMM + Beta-B
Comments Post-test contrast. Mean difference in change.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < .001
Comments Bonferoni adjusted critical value p = .0083.
Method t-test, 2 sided
Comments Degrees of freedom = 1 and 122.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.1
Parameter Dispersion
Type: Standard Deviation
Value: 1.26
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection OAT + Placebo (PL), OAT + Beta Blocker (Beta-B)
Comments Post-test contrast. Mean difference in change.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value > .02
Comments Bonferoni adjusted critical value p = .0083.
Method t-test, 2 sided
Comments Degrees of freedom = 1 and 106.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.5
Parameter Dispersion
Type: Standard Deviation
Value: 1.20
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection OAT + Placebo (PL), OAT + BMM + PL
Comments Post-test contrast. Mean difference in change.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >.79
Comments Bonferoni adjusted critical value p = .0083.
Method t-test, 2 sided
Comments Degrees of freedom = 1 and 108.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.1
Parameter Dispersion
Type: Standard Deviation
Value: 1.35
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection OAT + Beta Blocker (Beta-B), OAT + BMM + PL
Comments Post-test contrast. Mean difference in change.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >.02
Comments Bonferoni adjusted critical value p = .0083.
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.6
Parameter Dispersion
Type: Standard Deviation
Value: 1.43
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change in Quality of Life at Month 10
Hide Description Change in Migraine Specific Quality of Life Questionnaire (MSQL; Martin, et al., 2000: v 2.1) scores at Month 10 relative to OAT run-in (Month 1). The MSQL is a 14-item self-report measure that assesses the impact of migraine. The total score ranges from 14 to 84 with higher scores reflecting greater impairment.
Time Frame Change from Month 1 to Month 10
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy analyses were intent-to-treat analyses that included all randomized (N = 232) participants.
Arm/Group Title OAT + Placebo (PL) OAT + Beta Blocker (Beta-B) OAT + BMM + PL OAT + BMM + Beta-B
Hide Arm/Group Description:
Optimal Acute Therapy plus Beta Blocker Placebo
Optimal Acute Therapy plus Beta Blocker (propranolol or nadolol)
Optimal Acute Therapy plus Behavioral Migraine Management plus placebo
Optimal Acute Therapy plus Behavioral Migraine Management plus Beta Blocker (propranolol or nadolol)
Overall Number of Participants Analyzed 55 53 55 69
Mean (95% Confidence Interval)
Unit of Measure: Scores on a scale
-7.1
(-7.8 to -6.3)
-7.1
(-7.7 to -6.6)
-8.6
(-8.9 to -8.2)
-13.0
(-13.5 to -12.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OAT + Placebo (PL), OAT + Beta Blocker (Beta-B), OAT + BMM + PL, OAT + BMM + Beta-B
Comments Omnibus test:A mixed model with fixed effects for treatment, time (defined as the natural log of months), and the treatment-by-time interaction and pretreatment Migraine Specific Quality of Life scores as covariate was used to obtain maximum likelihood estimates of missing values and to evaluate treatment effects (using the PROC MIXED procedure in SAS statistical software, version 9; www. sas.com).A significant treatment by time interaction (p < .05, 2-tailed) was followed by post-tests
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.005
Comments Post tests consisted of 6 pair wise contrasts: The first 3 contrasts compared each of the 3 additive treatments (Trial Arms 2, 3, 4) to OAT + PL (Trial arm 1); three additional contrasts compared the 3 additive treatments to one another.
Method Mixed Models Analysis
Comments A Bonferoni procedure controlled the familywise type I error for the 6 contrasts at .05. Adjusted p=.0083.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection OAT + Placebo (PL), OAT + BMM + PL
Comments Post-test contrast. Mean difference in change.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < .001
Comments Bonferoni adjusted critical value p = .0083.
Method t-test, 2 sided
Comments Degrees of freedom = 1 and 108.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.5
Parameter Dispersion
Type: Standard Deviation
Value: 2.18
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection OAT + Placebo (PL), OAT + BMM + Beta-B
Comments Post-test contrast. Mean difference in change.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < .001
Comments Bonferoni adjusted critical value p = .0083.
Method t-test, 2 sided
Comments Degrees of freedom = 1 and 122.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 6.0
Parameter Dispersion
Type: Standard Deviation
Value: 2.41
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection OAT + Beta Blocker (Beta-B), OAT + BMM + PL
Comments Post-test contrast. Mean difference in change.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < .001
Comments Bonferoni adjusted critical value p = .0083.
Method t-test, 2 sided
Comments Degrees of freedom = 1 and 106.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.4
Parameter Dispersion
Type: Standard Deviation
Value: 1.67
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection OAT + Beta Blocker (Beta-B), OAT + BMM + Beta-B
Comments Post-test contrast. Mean difference in change.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments Bonferoni adjusted critical value p = .0083.
Method t-test, 2 sided
Comments Degrees of freedom = 1 and 120.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 5.9
Parameter Dispersion
Type: Standard Deviation
Value: 2.03
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection OAT + BMM + PL, OAT + BMM + Beta-B
Comments Post-test contrast. Mean difference in change.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < .001
Comments Bonferoni adjusted critical value p = .0083.
Method t-test, 2 sided
Comments Degrees of freedom = 1 and 122.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 4.5
Parameter Dispersion
Type: Standard Deviation
Value: 1.83
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection OAT + Placebo (PL), OAT + Beta Blocker (Beta-B)
Comments Post-test contrast. Mean difference in change.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >.87
Comments Bonferoni adjusted critical value p = .0083.
Method t-test, 2 sided
Comments Degrees of freedom = 1 and 106.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.1
Parameter Dispersion
Type: Standard Deviation
Value: 2.38
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change in Number of Migraine Episodes Per 30 Days at Month 16.
Hide Description Change in number of migraine episodes (with 24 hours pain free period required between episodes) per 30 days from OAT run-in (Month 1) to Month 16. Assessed by participant daily electronic diary.
Time Frame Change from Month 1 to Month 16
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy analyses were intent-to-treat analyses that included all randomized (N = 232) participants.
Arm/Group Title OAT + Placebo (PL) OAT + Beta Blocker (Beta-B) OAT + BMM + PL OAT + BMM + Beta-B
Hide Arm/Group Description:
Optimal Acute Therapy plus Beta Blocker Placebo
Optimal Acute Therapy plus Beta Blocker (propranolol or nadolol)
Optimal Acute Therapy plus Behavioral Migraine Management plus placebo
Optimal Acute Therapy plus Behavioral Migraine Management plus Beta Blocker (propranolol or nadolol)
Overall Number of Participants Analyzed 55 53 55 69
Mean (95% Confidence Interval)
Unit of Measure: Number of Migraine Episodes
-2.5
(-2.6 to -2.3)
-2.5
(-2.8 to -2.2)
-2.7
(-2.9 to -2.5)
-3.8
(-4.0 to -3.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OAT + Placebo (PL), OAT + BMM + Beta-B
Comments Post-test contrast. Mean difference in change.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments Bonferoni adjusted critical value p = .0083.
Method t-test, 2 sided
Comments Degrees of freedom = 1 and 122.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.3
Parameter Dispersion
Type: Standard Deviation
Value: 0.77
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection OAT + Placebo (PL), OAT + Beta Blocker (Beta-B)
Comments Post-test contrast. Mean difference in change.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value > .83
Comments Bonferoni adjusted critical value p = .0083.
Method t-test, 2 sided
Comments Degrees of freedom = 1 and 106.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.0
Parameter Dispersion
Type: Standard Deviation
Value: 0.79
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection OAT + Placebo (PL), OAT + BMM + PL
Comments Post-test contrast. Mean difference in change.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value > .05
Comments Bonferoni adjusted critical value p = .0083.
Method t-test, 2 sided
Comments Degrees of freedom = 1 and 108.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.2
Parameter Dispersion
Type: Standard Deviation
Value: 0.67
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection OAT + BMM + PL, OAT + BMM + Beta-B
Comments Significant post-test contrast. Mean difference in change.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < .001
Comments Bonferoni adjusted critical value p = .0083.
Method t-test, 2 sided
Comments Degrees of freedom = 1 and 122.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.1
Parameter Dispersion
Type: Standard Deviation
Value: 0.86
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection OAT + Beta Blocker (Beta-B), OAT + BMM + Beta-B
Comments Post-test contrast. Mean difference in change.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments Bonferoni adjusted critical value p = .0083.
Method t-test, 2 sided
Comments Degrees of freedom = 1 and 120.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.3
Parameter Dispersion
Type: Standard Deviation
Value: 0.95
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection OAT + Beta Blocker (Beta-B), OAT + BMM + PL
Comments Post-test contrast. Mean difference in change.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value > .20
Comments Bonferoni adjusted critical value p = .0083.
Method t-test, 2 sided
Comments Degrees of freedom = 1 and 106.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.2
Parameter Dispersion
Type: Standard Deviation
Value: 0.89
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change in the Number of Migraine Days Per 30 Days at Month 16
Hide Description Change in the number of migraine days per 30 days at Month 16 relative to the OAT run-in (Month 1). Assessed by participant electronic diary.
Time Frame Change form Month 1 to Month 16
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy analyses were intent-to-treat analyses that included all randomized (N = 232) participants.
Arm/Group Title OAT + Placebo (PL) OAT + Beta Blocker (Beta-B) OAT + BMM + PL OAT + BMM + Beta-B
Hide Arm/Group Description:
Optimal Acute Therapy plus Beta Blocker Placebo
Optimal Acute Therapy plus Beta Blocker (propranolol or nadolol)
Optimal Acute Therapy plus Behavioral Migraine Management plus placebo
Optimal Acute Therapy plus Behavioral Migraine Management plus Beta Blocker (propranolol or nadolol)
Overall Number of Participants Analyzed 55 53 55 69
Mean (95% Confidence Interval)
Unit of Measure: Number of Days
-3.9
(-4.3 to -3.5)
-4.5
(-5.1 to -4.0)
-4.1
(-4.5 to -3.8)
-6.1
(-6.6 to -5.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OAT + Placebo (PL), OAT + BMM + Beta-B
Comments Post-test contrast. Mean difference in change.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments Bonferoni adjusted critical value p = .0083.
Method t-test, 2 sided
Comments Degrees of freedom = 1 and 122.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.2
Parameter Dispersion
Type: Standard Deviation
Value: 1.70
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection OAT + Beta Blocker (Beta-B), OAT + BMM + Beta-B
Comments Post-test contrast. Mean difference in change.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments Bonferoni adjusted critical value p = .0083.
Method t-test, 2 sided
Comments Degrees of freedom = 1 and 120.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.6
Parameter Dispersion
Type: Standard Deviation
Value: 1.96
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection OAT + BMM + PL, OAT + BMM + Beta-B
Comments Post-test contrast. Mean difference in change.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < .001
Comments Bonferoni adjusted critical value p = .0083.
Method t-test, 2 sided
Comments Degrees of freedom = 1 and 122.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.0
Parameter Dispersion
Type: Standard Deviation
Value: 1.69
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection OAT + Placebo (PL), OAT + Beta Blocker (Beta-B)
Comments Post-test contrast. Mean difference in change.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >.04
Comments Bonferoni adjusted critical value p = .0083.
Method t-test, 2 sided
Comments Degrees of freedom = 1 and 106.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.6
Parameter Dispersion
Type: Standard Deviation
Value: 1.69
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection OAT + Placebo (PL), OAT + BMM + PL
Comments Post-test contrast. Mean difference in change.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.33
Comments Bonerfoni adjusted critical value p = .0083.
Method t-test, 2 sided
Comments Degrees of freedom = 1 and 108.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.2
Parameter Dispersion
Type: Standard Deviation
Value: 1.34
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection OAT + Beta Blocker (Beta-B), OAT + BMM + PL
Comments Post-test contrast. Mean difference in change.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.21
Comments Bonferoni adjusted critical value p = .0083.
Method t-test, 2 sided
Comments Degrees of freedom = 1 and 106.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.2
Parameter Dispersion
Type: Standard Deviation
Value: 1.68
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change in Quality of Life at Month 16
Hide Description Change in Migraine Specific Quality of Life Questionnaire (MSQL; Martin, et al., 2000: v 2.1) scores relative to OAT run-in. The MSQL is a 14-item self-report measure that assesses the impact of migraine. The total score ranges from 14 to 84 with higher scores reflecting greater impairment.
Time Frame Change from Month 1 to Month 16
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy analyses were intent-to-treat analyses that included all randomized (N = 232) participants.
Arm/Group Title OAT + Placebo (PL) OAT + Beta Blocker (Beta-B) OAT + BMM + PL OAT + BMM + Beta-B
Hide Arm/Group Description:
Optimal Acute Therapy plus Beta Blocker Placebo
Optimal Acute Therapy plus Beta Blocker (propranolol or nadolol)
Optimal Acute Therapy plus Behavioral Migraine Management plus placebo
Optimal Acute Therapy plus Behavioral Migraine Management plus Beta Blocker (propranolol or nadolol)
Overall Number of Participants Analyzed 55 53 55 69
Mean (95% Confidence Interval)
Unit of Measure: Scores on a scale
-8.8
(-9.5 to -8.1)
-8.5
(-9.4 to -7.6)
-9.6
(-10.3 to -9.0)
-15.2
(-16.0 to -14.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OAT + Placebo (PL), OAT + BMM + Beta-B
Comments Post-test contrast. Mean difference in change.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < .001
Comments Bonferoni adjusted critical value p = .0083.
Method t-test, 2 sided
Comments Degrees of freedom = 1 and 122.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 6.4
Parameter Dispersion
Type: Standard Deviation
Value: 3.00
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection OAT + Beta Blocker (Beta-B), OAT + BMM + Beta-B
Comments Post-test contrast. Mean difference in change.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < .001
Comments Bonferoni adjusted critical value p = .0083.
Method t-test, 2 sided
Comments Degrees of freedom = 1 and 122.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 6.7
Parameter Dispersion
Type: Standard Deviation
Value: 3.29
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection OAT + BMM + PL, OAT + BMM + Beta-B
Comments Post-test contrast. Mean difference in change.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < .001
Comments Bonferoni adjusted critical value p = .0083.
Method t-test, 2 sided
Comments Degrees of freedom = 1 and 122.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 5.6
Parameter Dispersion
Type: Standard Deviation
Value: 2.99
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection OAT + Placebo (PL), OAT + Beta Blocker (Beta-B)
Comments Post-test contrast. Mean difference in change.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.56
Comments Bonferoni adjusted critical value p = .0083.
Method t-test, 2 sided
Comments Degrees of freedom = 1 and 106.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.3
Parameter Dispersion
Type: Standard Deviation
Value: 2.85
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection OAT + Placebo (PL), OAT + BMM + PL
Comments Post-test contrast. Mean difference in change.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.08
Comments Bonferoni adjusted critical value p = .0083.
Method t-test, 2 sided
Comments Degrees of freedom = 1 and 108.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.8
Parameter Dispersion
Type: Standard Deviation
Value: 2.45
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection OAT + Beta Blocker (Beta-B), OAT + BMM + PL
Comments Post-test contrast. Mean difference in change.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.03
Comments Bonferoni adjusted critical value p = .0083.
Method t-test, 2 sided
Comments Degrees of freedom = 1 and 106.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.1
Parameter Dispersion
Type: Standard Deviation
Value: 2.83
Estimation Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title OAT + Placebo (PL) at Month 5 OAT + Beta-Blocker at Month 5 OAT + BMM + PL at Month 5 OAT + BMM + Beta-Blocker at Month 5
Hide Arm/Group Description Optimal Acute Therapy (OAT) + Beta-Blocker (Propranolol/ Nadolol)Placebo. Side-effects (Fatigue, Gastrointestinal Distress, Insomnia, Lightheaded or Dizzy, Difficulty Concentrating, Depression, Weight Gain, Exercise Intolerance, Nightmares, Drowsiness or Other side effect at Month 5 following dose adjustment. Optimal Acute Therapy (OAT) + Beta-Blocker (Propranolol/Nadolol. Side-effects (Fatigue, Gastrointestinal Distress, Insomnia, Lightheaded or Dizzy, Difficulty Concentrating, Depression, Weight Gain, Exercise Intolerance, Nightmares, Drowsiness or other side-effect assessed after dose adjustment(Month 5).

Optimal Acute Therapy + Behavioral Migraine Management(BMM) + Beta-Blocker(Propranolol/Nadolol) Placebo.

Side-effects (Fatigue, Gastrointestinal Distress, Insomnia, Lightheaded or Dizzy, Difficulty Concentrating, Depression, Weight Gain, Exercise Intolerance, Nightmares, Drowsiness or other side-effect)as assessed after dose adjustment(Month 5).

Optimal Acute Therapy (OAT)+ Behavioral Migraine Management (BMM)+ Beta-Blocker(Propranolol/Nadolol).

Side-effects (Fatigue, Gastrointestinal Distress, Insomnia, Lightheaded or Dizzy, Difficulty Concentrating, Depression, Weight Gain, Exercise Intolerance, Nightmares, Drowsiness or other side effect) assessed after dose adjustment(Month 5).

All-Cause Mortality
OAT + Placebo (PL) at Month 5 OAT + Beta-Blocker at Month 5 OAT + BMM + PL at Month 5 OAT + BMM + Beta-Blocker at Month 5
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
OAT + Placebo (PL) at Month 5 OAT + Beta-Blocker at Month 5 OAT + BMM + PL at Month 5 OAT + BMM + Beta-Blocker at Month 5
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/55 (0.00%)      0/53 (0.00%)      0/55 (0.00%)      0/69 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
OAT + Placebo (PL) at Month 5 OAT + Beta-Blocker at Month 5 OAT + BMM + PL at Month 5 OAT + BMM + Beta-Blocker at Month 5
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3      7      2      2    
General disorders         
Fatigue   3/44 (6.82%)  3 7/42 (16.67%)  7 2/42 (4.76%)  2 2/48 (4.17%)  2
Indicates events were collected by systematic assessment
No side effect reached the 5% reporting threshold at either the Month 10 or the Month 16 assessment.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Kenneth Holroyd
Organization: Ohio University
Phone: (740) 593-1085
Responsible Party: Kenneth Holroyd, Distinguished Professor. Department of Psychology, Ohio University
ClinicalTrials.gov Identifier: NCT00910689     History of Changes
Other Study ID Numbers: 2R01NS032374 ( U.S. NIH Grant/Contract )
NS32374
First Submitted: November 24, 2008
First Posted: June 1, 2009
Results First Submitted: November 24, 2008
Results First Posted: June 1, 2009
Last Update Posted: November 22, 2016