Drug and Non-Drug Treatment Of Severe Migraine

Migraine Headache Clinical Trial

— TSM  

Official title:

Drug and Non-Drug Treatment of Severe Migraine

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00910689
• Other study ID #: 2RO1NS32374
• Secondary ID: NS32374
• Status: Completed
• Phase: Phase 4
• First received: November 24, 2008
• Last updated: June 4, 2009
• Start date: July 2001
• Est. completion date: November 2005

Study information

• Verified date: June 2009
• Source: Ohio University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 232
• Est. completion date: November 2005
• Est. primary completion date: November 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Migraine Disorders
• Migraine Headache

Intervention

Drug:
• Propranolol or nadolol
Treatment initiated with 1 capsule (60 mg long acting propranolol hydrochloride) and increased to 3 capsules (180 mg) at week 12 as tolerated. If subject does not tolerate at least 2 capsules (120 mg) of propranolol hydrochloride-LA, and in treating neurologist's judgment are unimproved, subject switched to second medication (nadolol). Participants initially receive a single 40 mg capsule of nadolol and increased to 2 capsules (80 mg) as tolerated. At week 12 dose stabilized at highest tolerated level. In evaluation phase, an increase to 4 capsules of long acting propranolol hydrochloride (240 mg) or 3 capsules of nadolol (120 mg) permitted.
• Placebo control
Placebo

Behavioral:
• Behavioral Migraine Management (BMM)
Session 1: Overview of the pathophysiology of migraine; introduce muscle stretching, deep breathing, PMR, imagery; Session 2: Development trigger management strategy; Use early warning signs as a cue to use behavioral migraine management and acute medication; Session 3:(a) continue with "basic" migraine management skills if these skills have not been mastered;(b) introduce cognitive-behavioral stress-management, if stress is a salient migraine trigger;(c) introduce thermal biofeedback ("hand warming") training with a portable home thermal biofeedback device, if stress is not a notable migraine trigger. Session 4: Review problems using various behavioral migraine management skills; Prepare written migraine management plan; Relapse prevention addressed

Drug:
• Optimal Acute Therapy
This acute therapy protocol emphasized treatment with a 5-HT1B/D-agonist or triptan. Nonsteroidal anti-inflammatory (NSAID; ibuprofen) and anti-emetic (metoclopramide) medication could be added as needed. The choice of triptans (rizatriptan®, sumatriptan®), the route(s) of triptan administration (oral, nasal spray, subcutaneous injection), and the addition of a NSAID, or anti-emetic were tailored to participant preference, treatment history and acute therapy response. Individualized handouts and a phone call (week 3) of the OAT Run-in were used to help participants evaluate and optimize their acute therapy.

Locations

Country	Name	City	State
United States	Ohio University	Athens	Ohio
United States	OrthoNeuro, Inc.	Westerville	Ohio

Sponsors (4)

Lead Sponsor	Collaborator
Ohio University	GlaxoSmithKline, Merck Sharp & Dohme Corp., National Institute of Neurological Disorders and Stroke (NINDS)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Martin BC, Pathak DS, Sharfman MI, Adelman JU, Taylor F, Kwong WJ, Jhingran P. Validity and reliability of the migraine-specific quality of life questionnaire (MSQ Version 2.1). Headache. 2000 Mar;40(3):204-15. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Number of Migraine Episodes Per 30 Days at Month 10.		Change from Month 1 to Month 10	No
Secondary	Change in the Number of Migraine Days Per 30 Days at Month 10		Change from Month 1 to Month 10	No
Secondary	Change in Quality of Life at Month 10		Change from Month 1 to Month 10	No
Secondary	Change in Number of Migraine Episodes Per 30 Days at Month 16.		Change from Month 1 to Month 16	No
Secondary	Change in the Number of Migraine Days Per 30 Days at Month 16		Change form Month 1 to Month 16	No
Secondary	Change in Quality of Life at Month 16		Change from Month 1 to Month 16	No