Drug and Non-Drug Treatment Of Severe Migraine

Phase 4

Completed

Conditions: Migraine Headache

Interventions: Drug: Propranolol or nadolol
Drug: Placebo control
Behavioral: Behavioral Migraine Management (BMM)
Drug: Optimal Acute Therapy

Registration Number: NCT00910689

Lead Sponsor: Ohio University

Brief Summary: The purpose of this study is to determine if the addition of preventive medication, behavior migraine management or the combination of preventive medication and behavior migraine management improves the outcome of optimal acute therapy for frequent migraines.

Detailed Description: During the 5 week Optimal Acute Therapy (OAT) Run in (Month 1) all participants who met initial inclusion criteria received "optimal" acute therapy (OAT). At the end of the OAT Run-in, participants who continued to meet the migraine severity criteria were stratified by sex and randomized via a computerized randomization procedure to the four added treatments: Beta Blocker Placebo (PL), Beta Blocker (Propranolol LA or Nadolol), Behavioral Migraine Management (BMM) + PL, or BMM + Beta Blocker. Each of the 4 treatment protocols required 4 monthly clinic visits and 3 telephone contacts during the 3 month Treatment/Dose Adjustment Phase (Month 2 to Month 4) where Beta Blocker or PL dose was adjusted and BMM was administered. During the 12 month (Month 5 to Month 16) Evaluation Phase clinic visits were scheduled at Month 5, Month 7, Month 10 (the Primary End Point), Month 13 and Month 16. Treatment conditions were blinded only for the preventive medication (Beta Blocker, Placebo) component, and not for the administration of BMM. Electronic headache diary recordings are obtained for the full 16 months of the trial, including the 12 month evaluation phase, and migraine-related impairments in quality of life are assessed at multiple points over the 16 months of the trial.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 232

Inclusion Criteria

18 to 65 years
Diagnosis of migraine with or without aura (International Classification of Headache Disorders)
3 or more migraine episodes/month with disability for the past 6 months
Less than 20 total headache days/month for the past 6 months

Exclusion Criteria

Medication overuse headaches
Currently taking medications contraindicated by study protocol and unable or unwilling to withdraw
Concurrently undergoing counseling/psychotherapy treatment
Unable to read, understand or record information in study diaries, questionnaires, and migraine management manual.
Unable/unwilling to give written informed consent
History of exclusionary medical condition such as, but not limited to, epilepsy, heart disease, kidney disease, liver disease, hepatic or renal impairment, stroke, ischemic abdominal syndromes, peripheral vascular disease.
Uncontrolled hypertension at screening (sitting systolic pressure > 160 mmHg, diastolic pressure > 95 mmHg)
Fertile female who is breastfeeding, pregnant planning a pregnancy within the next year or is unwilling to use adequate contraception.
Has exclusionary medical condition such as but not limited to diabetes (insulin dependent), tuberculosis, bronchospastic disease (asthma), heart disease (or multiple risk factors for heart disease), angina pectoris, documented silent ischemia, or cardiac arrythmias requiring medication, or a clinically significant EKG abnormality.
Other pain diagnosis is primary presenting problem (e.g., fibromyalgia)
Has a substance abuse problem or a psychological disorder that prevents participation in study (e.g., unmanaged severe depression that requires immediate treatment or limits participation in home-based treatment)
Hypersensitivity, intolerance or contraindication to use of Propranolol, Nadolol, Sumatriptan, or Rizatriptan

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2	Propranolol or nadolol	Optimal Acute Therapy plus Beta Blocker (propranolol or nadolol)
3	Optimal Acute Therapy	Optimal Acute Therapy plus Behavioral Migraine Management plus Beta Blocker placebo
4	Behavioral Migraine Management (BMM)	Optimal Acute Therapy plus Behavioral Migraine Management plus Beta Blocker (propranolol or nadolol)
1	Optimal Acute Therapy	Optimal Acute Therapy plus Beta Blocker Placebo
3	Behavioral Migraine Management (BMM)	Optimal Acute Therapy plus Behavioral Migraine Management plus Beta Blocker placebo
1	Placebo control	Optimal Acute Therapy plus Beta Blocker Placebo
2	Optimal Acute Therapy	Optimal Acute Therapy plus Beta Blocker (propranolol or nadolol)
3	Placebo control	Optimal Acute Therapy plus Behavioral Migraine Management plus Beta Blocker placebo
4	Propranolol or nadolol	Optimal Acute Therapy plus Behavioral Migraine Management plus Beta Blocker (propranolol or nadolol)
4	Optimal Acute Therapy	Optimal Acute Therapy plus Behavioral Migraine Management plus Beta Blocker (propranolol or nadolol)

Primary Outcome Measures

Name	Time	Method
Change in Number of Migraine Episodes Per 30 Days at Month 10.	Change from Month 1 to Month 10	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.

Secondary Outcome Measures

Name	Time	Method
Change in the Number of Migraine Days Per 30 Days at Month 10	Change from Month 1 to Month 10	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.
Change in Quality of Life at Month 10	Change from Month 1 to Month 10	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.
Change in Number of Migraine Episodes Per 30 Days at Month 16.	Change from Month 1 to Month 16	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.
Change in the Number of Migraine Days Per 30 Days at Month 16	Change form Month 1 to Month 16	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.
Change in Quality of Life at Month 16	Change from Month 1 to Month 16	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.