Drug and Non-Drug Treatment Of Severe Migraine

NCT00910689 | Completed Phase 4 Results

• 2 other identifiers: 2R01NS032374NS32374
• Study Type: interventional
• Target: 232
• Locations: 1 country
• Sites: 2

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.

Conditions

Migraine Headache

Keywords

Migraine Headache; Preventive Therapy; Beta Blocker Medication; Behavior Therapy; Clinical Trial

Outcome Measures

Primary Outcomes (1)

• Change in Number of Migraine Episodes Per 30 Days at 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.

  Change from Month 1 to Month 10

Secondary Outcomes (5)

• Change in the Number of Migraine Days Per 30 Days at Month 10

  Change from Month 1 to Month 10

• Change in Quality of Life at Month 10

  Change from Month 1 to Month 10

• Change in Number of Migraine Episodes Per 30 Days at Month 16.

  Change from Month 1 to Month 16

• Change in the Number of Migraine Days Per 30 Days at Month 16

  Change form Month 1 to Month 16

• Change in Quality of Life at Month 16

  Change from Month 1 to Month 16

Study Arms (4)

1

PLACEBO COMPARATOR

Optimal Acute Therapy plus Beta Blocker Placebo

Drug: Placebo control; Drug: Optimal Acute Therapy

2

ACTIVE COMPARATOR

Optimal Acute Therapy plus Beta Blocker (propranolol or nadolol)

Drug: Propranolol or nadolol; Drug: Optimal Acute Therapy

3

ACTIVE COMPARATOR

Optimal Acute Therapy plus Behavioral Migraine Management plus Beta Blocker placebo

Drug: Placebo control; Behavioral: Behavioral Migraine Management (BMM); Drug: Optimal Acute Therapy

4

ACTIVE COMPARATOR

Optimal Acute Therapy plus Behavioral Migraine Management plus Beta Blocker (propranolol or nadolol)

Drug: Propranolol or nadolol; Behavioral: Behavioral Migraine Management (BMM); Drug: Optimal Acute Therapy

Interventions

Propranolol or nadolol DRUG

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.

Also known as: Inderal, Nadolol

2; 4

Placebo control DRUG

Placebo

1; 3

Behavioral Migraine Management (BMM) BEHAVIORAL

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

Also known as: Behavioral Treatment, BMM

3; 4

Optimal Acute Therapy DRUG

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.

Also known as: Imitrex®, Maxalt®, Reglan®, Advil®, Motrin®, Nuprin®

1; 2; 3; 4

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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
• 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.
• 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

Sponsors & Collaborators

• Ohio University: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• Merck Sharp & Dohme LLC: collaborator
• GlaxoSmithKline: collaborator

Study Sites (2)

Ohio University

Athens, Ohio, 45701, United States

Location

OrthoNeuro, Inc.

Westerville, Ohio, 43081, United States

Location

Related Publications (2)

• 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. doi: 10.1046/j.1526-4610.2000.00030.x.

  PMID: 10759923 BACKGROUND

• Holroyd KA, Cottrell CK, O'Donnell FJ, Cordingley GE, Drew JB, Carlson BW, Himawan L. Effect of preventive (beta blocker) treatment, behavioural migraine management, or their combination on outcomes of optimised acute treatment in frequent migraine: randomised controlled trial. BMJ. 2010 Sep 29;341:c4871. doi: 10.1136/bmj.c4871.

  PMID: 20880898 DERIVED

MeSH Terms

Conditions

Migraine Disorders

Interventions

Propranolol; Nadolol; Behavior Therapy; Sumatriptan; rizatriptan; Metoclopramide; Ibuprofen

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Psychotherapy; Behavioral Disciplines and Activities; Sulfonamides; Amides; Sulfones; Sulfur Compounds; Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Benzamides; para-Aminobenzoates; Aminobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Chlorobenzoates; Hydroxybenzoate Ethers; Hydroxybenzoates; Hydroxy Acids; Benzene Derivatives; Phenyl Ethers; Phenols; Phenylpropionates

Limitations and Caveats

No side effect reached the 5% reporting threshold at either the Month 10 or the Month 16 assessment.

Results Point of Contact

• Title: Kenneth Holroyd
• Organization: Ohio University

holroyd@ohio.edu

(740) 593-1085

Study Officials

• Kenneth A Holroyd, Ph.D.

  Ohio University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: November 24, 2008
• First Posted: June 1, 2009
• Study Start: July 1, 2001
• Primary Completion: November 1, 2005
• Study Completion: November 1, 2005
• Last Updated: November 22, 2016
• Results First Posted: June 1, 2009

Record last verified: 2016-10

Locations

US (2)