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Chronic MigrainePhase 4NCT02037425

Duration of Benefit for OnabotulinumtoxinA in Treatment of Chronic Migraine

A Phase 4 study testing onabotulinumtoxinA in people with Chronic Migraine, run by Cady, Roger, M.D. at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

To obtain a patient specific understanding of response to treatment with onabotulinumtoxinA by collecting and correlating pre and post treatment subject specific history, clinical outcomes, and histological changes. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Chronic Migraine
What is being tested?
onabotulinumtoxinA
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
44 participants
Where
1 siteUnited States
Study dates
Apr 2014to Sep 2015
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • male or female 18 years or older.
  • able to read, understand, and sign the informed consent.
  • a negative urine pregnancy test at visit 1, if female, and of childbearing potential. Note: If female of childbearing potential, subject must agree to maintain true abstinence or use one of the listed methods of birth control for the duration of the study: hormonal contraceptive, intrauterine device (IUD), condoms, diaphragm, and/or have a male partner who has undergone a successful vasectomy. The use of barrier contraceptive (condom or diaphragm) should always be supplemented with the use of a spermicide.
  • Note: To be considered not of childbearing potential, subject must be 6 weeks post-surgical bilateral oophorectomy, hysterectomy, bilateral tubal ligation, postmenopausal for at least one year.
  • at least a one year history of migraine
  • history of chronic migraine (with or without aura) according to the criteria of the International Classification of Headache Disorders (ICHD)-3 for at least 3 months prior to enrollment (Appendix I)
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  • able to differentiate migraine headache from any other headache they may experience (e.g., cluster headache)
  • onset of migraine before age 50
  • willing to provide responses to questionnaires and complete the online diary.
  • if taking migraine preventive(s), be on a stable dose of the preventive medication for at least 30 days prior to screening
  • concomitant medication dosages approved by the investigator
  • email and internet access for completion of online diary

Who cannot join

  • previously used onabotulinumtoxinA as a migraine preventative or has used onabotulinumtoxinA for any other reason during the prior year
  • female who is pregnant, planning to become pregnant during the study period, breast feeding, or is of childbearing potential and not practicing a reliable form of birth control
  • headache disorders outside ICHD-3 defined chronic migraine that cannot be easily distinguished from CM (Appendix I)
  • evidence of underlying pathology contributing to their headaches
  • any medical condition that may increase their risk with exposure to BTX including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, or any other significant disease that might interfere with neuromuscular function
  • profound atrophy or weakness of muscles in the target areas of injection
Show all 13Show fewer
  • skin conditions or infections at any of the injection sites
  • allergy or sensitivities to any component of the test medication
  • in the opinion of the investigator, has an active major psychiatric disorder including substance abuse and/or substance dependence within the last 12 months as determined by the investigator.
  • Medication Overuse Headache as defined by ICHD-3 criteria for opioid or butalbital containing products (Appendix II)
  • planning or requiring surgery during the study
  • a history of poor compliance with medical treatment
  • currently participating in an investigational drug study or has participated in an investigational drug study within the previous 30 days of the screening visit

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Clinvest/A Division of Banyan Group, Inc.

    Springfield, Missouri, 65807

Other trials in United States

About this study

Official title: Exploratory Study of the Natural History, Clinical Outcomes, and Neuronal Endplate Changes in Subjects Reporting Short Duration vs. Long Duration of Benefit for OnabotulinumtoxinA in Treatment of Chronic Migraine

To obtain a patient specific understanding of response to treatment with onabotulinumtoxinA by collecting and correlating pre and post treatment subject specific history, clinical outcomes, and histological changes.

Read the detailed description

Recognizing a commitment to evidence-based science as the pathway to optimize clinical outcomes for patients with chronic migraine (CM) we believe this investigator initiated study (IIS) will:

  1. Help clinicians recognize the importance of scheduling patients with CM at intervals not exceeding 12 weeks.
  2. Provide biopsy evidence supporting sensory mechanisms involved in the mechanism of action (MOA) of onabotulinumtoxinA (BTX). This does not exclude potential valuable contributions of denervation of motor neurons, but may support a more balanced and understandable mechanism for BTX in treating CM.
  3. Provide clinicians important educational information for patients to better manage expectations of using BTX in managing CM and answering critical questions such as:
  4. How long does it take for BTX to begin providing a clinical benefit?
  5. What is the expected duration of this benefit?
  • Failure to understand unmet expectations either real or otherwise results in defining BTX treatment as a failure by patients and/or clinicians.
  1. Provide validation for patients' reports of shorter duration of action of BTX so patients will not be misinterpreted as non-responders to BTX prematurely.
  2. Ascertain if subjects initially reporting short duration of BTX response continue to experience this similar pattern of effect with repeated injection cycles.
  3. Provide the first detailed longitudinal assessment of BTX response.
  4. Correlate the onset and duration of benefit for subjects receiving BTX.
  5. Observe factors predictive of duration of BTX response.

This study proposes to accomplish these goals through an exploratory comparison of the clinical efficacy and natural history of BTX measured at weekly time intervals. Subjects reporting short (<10 weeks) duration of benefit and subjects reporting long (>10 weeks) duration of clinical benefit will provide the primary comparison. Histological examinations (in a subset of subjects) of neuronal changes associated with regeneration of terminal neuronal endplates will be used to support these clinical observations. This study will follow subjects through 3 injection cycles or 36 weeks. Biopsies will be performed on consenting subjects prior to their first and second injection cycles.

Group Assignment

At Visit 3, subjects will be assigned to one of three groups (Groups A, B, C) based on their answers to the following questions:

  1. Since your last BTX treatment, do you think there has been improvement in your chronic migraine? If the answer to Q1 is yes, subject will answer Q2 and Q3. If the answer is no, subject is assigned to Group C and no further answers are required:
  2. How many days did it take for you to first notice benefit from BTX injections?
  3. How long did you feel you received benefit from BTX (number of weeks)?

Subjects will be assigned into 3 groups:

  1. Group A are subjects reporting 10 or less weeks of benefit from BTX;
  2. Group B are subjects reporting >10 weeks of benefit from BTX;
  3. Group C are subjects reporting no or minimal (< 30%) benefit from BTX.

Consistency of subjects' perception of BTX benefit at 12 weeks will be compared to responses at 24 and 36 weeks, though Group assignment will remain as defined at 12 weeks.

This exploratory study will be conducted at the Headache Care Center in Springfield, MO. Thirty-six subjects, 18 years and older with a history of chronic migraine will be enrolled. The study will consist of 5 visits for all subjects.

At Visit 1 (day 1 of baseline) the following study procedures will be performed:

  • Informed Consent obtained
  • Migraine, medical and medication history obtained
  • Physical and neurological exam performed
  • Urine pregnancy test performed if applicable
  • Vital signs collected

At Visit 2 (day 29 +/- 3 days) the following study procedures will be performed:

  • Update medical and medication history
  • Urine pregnancy test performed if applicable
  • Vital signs collected
  • Review baseline diary
  • Complete Migraine Disability Assessment Scale (MIDAS)
  • Complete Social Readjustment Rating Scale (SRRS)
  • Complete Beck Depression Inventory II (BDI-II)
  • Complete State-Trait Anxiety Inventory (STAI)
  • Complete Sleep Quality Questionnaire
  • Punch biopsy for neuronal regrowth (subset of subjects)
  • onabotulinumtoxinA injections

At Visit 3 (day 113 +/- 3 days) the following study procedures will be performed:

  • Update medical and medication history
  • Urine pregnancy test performed if applicable
  • Vital signs collected
  • Complete Subject Global Impression of Change (SGIC)
  • Complete Physician Global Impression of Change (PGIC)
  • Complete Migraine Disability Assessment Scale (MIDAS)
  • Complete Social Readjustment Rating Scale (SRRS)
  • Complete Beck Depression Inventory II (BDI-II)
  • Complete State-Trait Anxiety Inventory (STAI)
  • Complete Sleep Quality Questionnaire
  • Complete duration of response to onabotulinumtoxinA questions
  • Punch biopsy for neuronal regrowth (subset of subjects)
  • onabotulinumtoxinA injections

At Visit 4 (day 197 +/- 3 days) the following study procedures will be performed:

  • Update medical and medication history
  • Urine pregnancy test performed if applicable
  • Vital signs collected
  • Complete Subject Global Impression of Change (SGIC)
  • Complete Physician Global Impression of Change (PGIC)
  • Complete Migraine Disability Assessment Scale (MIDAS)
  • Complete Social Readjustment Rating Scale (SRRS)
  • Complete Beck Depression Inventory II (BDI-II)
  • Complete State-Trait Anxiety Inventory (STAI)
  • Complete Sleep Quality Questionnaire
  • Complete duration of response to onabotulinumtoxinA questions
  • onabotulinumtoxinA injections

At Visit 5 (day 281 +/- 3 days) the following study procedures will be performed:

  • Update medical and medication history
  • Urine pregnancy test performed if applicable
  • Vital signs collected
  • Complete Subject Global Impression of Change (SGIC)
  • Complete Physician Global Impression of Change (PGIC)
  • Complete Migraine Disability Assessment Scale (MIDAS)
  • Complete Social Readjustment Rating Scale (SRRS)
  • Complete Beck Depression Inventory II (BDI-II)
  • Complete State-Trait Anxiety Inventory (STAI)
  • Complete Sleep Quality Questionnaire
  • Complete duration of response to onabotulinumtoxinA questions
Being tested
onabotulinumtoxinA
Keywords
Chronic Migraine, onabotulinumtoxinA, Headache, Migraine, Neuronal regrowth, Botox
Medical subject headings
Headache, Migraine Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • onabotulinumtoxinADrug

    Also called Botox

    BOTOX® (Formulation Number 9060X) contains 200 International Units (IU) of Clostridium botulinum Toxin Type A, reconstituted with 4 cc of normal saline providing 5 units per 0.1 cc. At visit 2, subjects will receive their first treatment at Day 29 (+/-3 days). All subjects will receive 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas. Injections will be repeated at day 113 (+/- 3 days) and at day 197 (+/- 3 days).

Study groups in NCT02037425
Study groupRoleWhat they receive
onabotulinumtoxinAOtherAt visit 2, subjects will receive their first treatment at Day 29 (+/-3 days). All subjects will receive 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas. Injections will be repeated at day 113 (+/- 3 days) and at day 197 (+/- 3 days).
Receives: Drug: onabotulinumtoxinA

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Subject Global Impression of Change

    Changes in the Subject's Global Impression of Change (SGIC) measured at weeks 12, 24, and 36 for Groups A, B, and C. Subject global impression of change was measured on a 7 point scale with 0 being Very Much Worse and 7 Very Much Improved.

    Measured: Weeks 12, 24, and 36 Post Randomization

  2. Duration of onabotulinumtoxinA Over 3 Injection Cycles in Groups A, B, and C

    Compare the duration of onabotulinumtoxinA response through the 3 injection cycles of the study for Groups A, B, and C as measured by headache days during each period (Baseline (28 days), Treatment Period 1(84 days), Treatment Period 2(84 days), and Treatment Period 3(84 days). Duration of response is defined as a 30% reduction in the number of headache days compared to baseline.

    Measured: From day 29 (first day of injection cycle 1) to day 281 (84th day of injection cycle 3) plus or minus 12 days

Secondary outcomes (10)

  1. Headache Days

    Comparison of headache days per month over each injection cycle between Groups A, B, and C (Baseline (28 days), Treatment Period 1(84 days), Treatment Period 2(84 days), and Treatment Period 3(84 days). Subjects will remain in their assigned groups based on assessment at 12 weeks.

    Measured: From day 29 (first day of injection cycle 1) to day 281 (84th day of injection cycle 3) plus or minus 12 days

  2. Migraine Disability Assessment Scale (MIDAS)

    Comparison between Group A, B, and C for MIDAS total scores (effect migraine headaches have on subjects daily function) measured at baseline and weeks 12, 24, and 36.

    Total score of disability ranges:

    • 0 to 5, MIDAS Grade I, Little or no disability
    • 6 to 10, MIDAS Grade II, Mild disability
    • 11 to 20, MIDAS Grade III, Moderate disability
    • 21+, MIDAS Grade IV, Severe disability Score ranges from 0-450. No subscales are present.

    Measured: Baseline, Week 12, Week 24, and Week 36 Post Randomization

  3. Social Readjustment Rating Scale (SRRS)

    Comparison between Group A, B, and C for SRRS scores (impact of common stressors) measured at baseline and weeks 12, 24, and 36. Scores can range from 0 to an undetermined amount, as subjects are allowed to rate unlisted events according to their own sense of stress. A total lower than 150 suggests a low level of stress and a low probability of developing a stress-related disorder. Scores greater than 150 suggest higher levels of stress and higher probabilities of developing stress-related disorders.

    Measured: Baseline, Week 12, Week 24, and Week 36 Post Randomization

  4. Physician Global Impression of Change (PGIC)

    Comparison between Group A, B, and C for PGIC scores measured at weeks 12, 24, and 36. the PGIC scale scores range from 0-7 with 0 being Very Much Worse and 7 being Very Much Improved. A higher score indicates a greater impression of change.

    Measured: Week 12, Week 24, and Week 36 Post Randomization

  5. Beck Depression Inventory II (BDI-II)

    Comparison between Group A, B, and C for BDI-II scores measured at baseline and weeks 12, 24, and 36. A total score of 0-10 = these ups and downs are considered normal, 11-16 = mild mood disturbance,17-20 = borderline clinical depression, 21-30 = moderate depression, 31-40 = severe depression, over 40 = extreme depression

    Measured: Baseline, Week 12, Week 24, and Week 36 Post Randomization

  6. State-Trait Anxiety Inventory (STAI)

    Comparison between Group A, B, and C for STAI scores measured at baseline and weeks 12, 24, and 36. Scores range from 20-80, with 20 indicating lower levels of anxiety most generally, and 80 indicating higher levels of anxiety most generally.

    Measured: Baseline, Week 12, Week 24, and Week 36 Post Randomization

  7. Sleep Quality Question

    Comparison between Group A, B, and C for sleep quality scores measured at baseline and weeks 12, 24, and 36 post-randomization. A single sleep quality question was asked indicating quality of sleep over the past four weeks. The scale ranged from 1-5, with 1 being very poor quality and 5 being very good quality of sleep.

    Measured: Baseline, Week 12, Week 24, and Week 36 Post Randomization

  8. Acute Medication Usage

    Comparison of acute medication usage between Groups A, B, and C during baseline, Treatment Period 1, 2, and 3.

    Measured: From day 1 (first day of baseline) to day 281 (84th day of injection cycle 3) plus or minus 12 days

  9. Consistency of Response to onbotulinumtoxinA Over Three Injection Cycles

    Compare the consistency of duration of onabotulinumtoxinA response by the group assignment at 12 weeks to assessments at 24, and 36 weeks evaluations as measured by the number of responders. A responder is defined as a 30% reduction from baseline in the number of headache days.

    Measured: Weeks 12, 24, and 36 Post Randomization

  10. Duration of onabotulinumtoxinA Over 3 Injection Cycles

    Compare duration of benefit of onabotulinumtoxinA response through 3 injection cycles as measured by headache days per week (including the last 4 weeks of every injection cycle). A percent of responders was calculated using a 30% reduction of the number of headache days compared to average number of headache per week during baseline.

    Measured: Weeks 9, 10, 11, 12, 21, 22, 23, 24, 33, 34, 35, 36 Post Randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Jan 2014 (estimated)
  2. Study startApr 2014
  3. Primary completionSep 2015
  4. Study completionSep 2015

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
44 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02037425
Sponsor's protocol ID
13-002AL
Status last verified
Jul 2016
First submitted
14 Jan 2014
Last updated
11 Aug 2016
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing onabotulinumtoxinA in people with Chronic Migraine, run by Cady, Roger, M.D. at 1 site 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 12 inclusion and 13 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 11 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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. 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 8 Mar 2016). 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?

Subject Global Impression of Change (time frame: Weeks 12, 24, and 36 Post Randomization). The study lists 2 primary outcomes in all. 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 NCT02037425.

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 11 Aug 2016.

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