Migraine HeadachePhase 4TSMNCT00910689
Drug and Non-Drug Treatment Of Severe Migraine
A Phase 4 study testing Propranolol or nadolol, Behavioral Migraine Management (BMM) and Optimal Acute Therapy in people with Migraine Headache, run by Ohio University at 2 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Migraine Headache
- What is being tested?
- Propranolol or nadolol, Behavioral Migraine Management (BMM) and Optimal Acute Therapy
- Type of treatment
- Pill or oral medicine, Injection or infusion, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 232 participants
- Where
- 2 sitesUnited States
- Study dates
- Jul 2001to Nov 2005
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 12Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Ohio University
Athens, Ohio, 45701
OrthoNeuro, Inc.
Westerville, Ohio, 43081
About this study
Official title: Drug and Non-Drug Treatment of Severe Migraine
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.
Read the 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.
- Conditions
- Migraine Headache
- Being tested
- Propranolol or nadolol, Placebo control, Behavioral Migraine Management (BMM), Optimal Acute Therapy
- Keywords
- Migraine Headache, Preventive Therapy, Beta Blocker Medication, Behavior Therapy, Clinical Trial
- Medical subject headings
- Migraine Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Propranolol or nadololDrug
Also called Inderal, 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 controlDrug
Placebo
Behavioral Migraine Management (BMM)Behavioural
Also called Behavioral Treatment, 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
Optimal Acute TherapyDrug
Also called Imitrex®, Maxalt®, Reglan®, Advil®
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.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Placebo comparator | Optimal Acute Therapy plus Beta Blocker Placebo Receives: Drug: Placebo control; Drug: Optimal Acute Therapy |
| 2 | Active comparator | Optimal Acute Therapy plus Beta Blocker (propranolol or nadolol) Receives: Drug: Propranolol or nadolol; Drug: Optimal Acute Therapy |
| 3 | Active comparator | Optimal Acute Therapy plus Behavioral Migraine Management plus Beta Blocker placebo Receives: 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) Receives: Drug: Propranolol or nadolol; Behavioral: Behavioral Migraine Management (BMM); Drug: Optimal Acute Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Change from Month 1 to Month 10
Secondary outcomes (5)
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.
Measured: Change from Month 1 to Month 10
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.
Measured: Change from Month 1 to Month 10
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.
Measured: Change from Month 1 to Month 16
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.
Measured: Change form Month 1 to Month 16
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.
Measured: Change from Month 1 to Month 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2009 (estimated)
- Study startJul 2001
- Primary completionNov 2005
- Study completionNov 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Migraine HeadacheStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 232 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ohio University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS), Merck Sharp & Dohme LLC, GlaxoSmithKline
- Investigators
- Kenneth A Holroyd, Ph.D., Principal investigator, Ohio University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00910689
- Sponsor's protocol ID
- 2R01NS032374
- Other IDs
- NS32374
- Acronym
- TSM
- Status last verified
- Oct 2016
- First submitted
- 24 Nov 2008
- Last updated
- 22 Nov 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 10759923Holroyd 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.
PubMed 20880898
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Drug and Non-Drug Treatment of Severe Migraine
- ClinicalTrials.gov ID
- NCT00910689
- Acronym / sponsor ID
- TSM / 2R01NS032374
- Conditions
- Migraine Headache
- Keywords
- Migraine Headache, Preventive Therapy, Beta Blocker Medication, Behavior Therapy, Clinical Trial
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 232 participants (actual)
- Lead sponsor
- Ohio UniversityUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS), Merck Sharp & Dohme LLC, GlaxoSmithKline
- Study start
- Jul 2001
- Primary completion
- Nov 2005 (actual)
- Study completion
- Nov 2005 (actual)
- First posted
- 1 Jun 2009 (estimated)
- Results
- Posted 1 Jun 2009
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1 | Placebo comparator | Drug: Placebo control, Drug: Optimal Acute TherapyOptimal Acute Therapy plus Beta Blocker Placebo |
| 2 | Active comparator | Drug: Propranolol or nadolol, Drug: Optimal Acute TherapyOptimal Acute Therapy plus Beta Blocker (propranolol or nadolol) |
| 3 | Active comparator | Drug: Placebo control, Behavioral: Behavioral Migraine Management (BMM), Drug: Optimal Acute TherapyOptimal Acute Therapy plus Behavioral Migraine Management plus Beta Blocker placebo |
| 4 | Active comparator | Drug: Propranolol or nadolol, Behavioral: Behavioral Migraine Management (BMM), Drug: Optimal Acute TherapyOptimal Acute Therapy plus Behavioral Migraine Management plus Beta Blocker (propranolol or nadolol) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Propranolol or nadololAlso: Inderal, NadololTreatment 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. | Drug | 2, 4 |
| Placebo controlPlacebo | Drug | 1, 3 |
| Behavioral Migraine Management (BMM)Also: Behavioral Treatment, BMMSession 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 | Behavioural | 3, 4 |
| Optimal Acute TherapyAlso: Imitrex®, Maxalt®, Reglan®, Advil®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. | Drug | 1, 2, 3, 4 |
Primary outcome
Change in Number of Migraine Episodes Per 30 Days at Month 10.
Time frame: 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.
5 secondary outcomes
Change in the Number of Migraine Days Per 30 Days at Month 10
Time frame: Change from Month 1 to Month 10
Change in Quality of Life at Month 10
Time frame: Change from Month 1 to Month 10
Change in Number of Migraine Episodes Per 30 Days at Month 16.
Time frame: Change from Month 1 to Month 16
Change in the Number of Migraine Days Per 30 Days at Month 16
Time frame: Change form Month 1 to Month 16
Change in Quality of Life at Month 16
Time frame: Change from Month 1 to Month 16
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 10759923Martin 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.
- Derived from this study: PubMed 20880898Holroyd 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kenneth A Holroyd, Ph.D. principal investigator
Ohio University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Propranolol or nadolol, Behavioral Migraine Management (BMM) and Optimal Acute Therapy in people with Migraine Headache, run by Ohio University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Jun 2009). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Number of Migraine Episodes Per 30 Days at Month 10. (time frame: Change from Month 1 to Month 10). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00910689, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2016.