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

Primary Purpose

Migraine Headache

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Propranolol or nadolol
Placebo control
Behavioral Migraine Management (BMM)
Optimal Acute Therapy
Sponsored by
Ohio University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Migraine Headache focused on measuring Migraine Headache, Preventive Therapy, Beta Blocker Medication, Behavior Therapy, Clinical Trial

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Ohio University
  • OrthoNeuro, Inc.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Placebo Comparator

Active Comparator

Active Comparator

Active Comparator

Arm Label

1

2

3

4

Arm 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 Beta Blocker placebo

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Change in the Number of Migraine Days Per 30 Days at 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 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 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 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 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.

Full Information

First Posted
November 24, 2008
Last Updated
October 7, 2016
Sponsor
Ohio University
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS), Merck Sharp & Dohme LLC, GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT00910689
Brief Title
Drug and Non-Drug Treatment Of Severe Migraine
Acronym
TSM
Official Title
Drug and Non-Drug Treatment of Severe Migraine
Study Type
Interventional

2. Study Status

Record Verification Date
October 2016
Overall Recruitment Status
Completed
Study Start Date
July 2001 (undefined)
Primary Completion Date
November 2005 (Actual)
Study Completion Date
November 2005 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Ohio University
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS), Merck Sharp & Dohme LLC, GlaxoSmithKline

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Migraine Headache
Keywords
Migraine Headache, Preventive Therapy, Beta Blocker Medication, Behavior Therapy, Clinical Trial

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
232 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Placebo Comparator
Arm Description
Optimal Acute Therapy plus Beta Blocker Placebo
Arm Title
2
Arm Type
Active Comparator
Arm Description
Optimal Acute Therapy plus Beta Blocker (propranolol or nadolol)
Arm Title
3
Arm Type
Active Comparator
Arm Description
Optimal Acute Therapy plus Behavioral Migraine Management plus Beta Blocker placebo
Arm Title
4
Arm Type
Active Comparator
Arm Description
Optimal Acute Therapy plus Behavioral Migraine Management plus Beta Blocker (propranolol or nadolol)
Intervention Type
Drug
Intervention Name(s)
Propranolol or nadolol
Other Intervention Name(s)
Inderal, Nadolol
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo control
Intervention Description
Placebo
Intervention Type
Behavioral
Intervention Name(s)
Behavioral Migraine Management (BMM)
Other Intervention Name(s)
Behavioral Treatment, BMM
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Optimal Acute Therapy
Other Intervention Name(s)
Imitrex®, Maxalt®, Reglan®, Advil®, Motrin®, Nuprin®
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in Number of Migraine Episodes Per 30 Days at Month 10.
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
Secondary Outcome Measure Information:
Title
Change in the Number of Migraine Days Per 30 Days at Month 10
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
Title
Change in Quality of Life at Month 10
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
Title
Change in Number of Migraine Episodes Per 30 Days at Month 16.
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
Title
Change in the Number of Migraine Days Per 30 Days at Month 16
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
Title
Change in Quality of Life at Month 16
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kenneth A Holroyd, Ph.D.
Organizational Affiliation
Ohio University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ohio University
City
Athens
State/Province
Ohio
ZIP/Postal Code
45701
Country
United States
Facility Name
OrthoNeuro, Inc.
City
Westerville
State/Province
Ohio
ZIP/Postal Code
43081
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
10759923
Citation
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.
Results Reference
background
PubMed Identifier
20880898
Citation
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.
Results Reference
derived

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Drug and Non-Drug Treatment Of Severe Migraine

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