A Study to Evaluate the Tolerability of Botox and Topiramate or Botox and Placebo and Effect on Cognitive Efficiency
Condition: Chronic Migraine
MeSH terms: Migraine Disorders
Intervention: onabotulinumtoxinA; Topiramate; Placebo
Intervention description: All subjects will receive a minimum dose of 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 at Visits 2-5.; Subjects randomized to the onabotulinumtoxinA + topiramate group will receive:
Week 1: topiramate 25 mg qhs Week 2: topiramate 25 mg bid Week 3: topiramate 25 mg q am + topiramate 50 mg qhs Week 4: topiramate 50 mg bid Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to remain in the Treatment Period.; Subjects randomized to the onabotulinumtoxinA + placebo group will receive:
Week 1: placebo 25 mg qhs Week 2: placebo 25 mg bid Week 3: placebo 25 mg q am + placebo 50 mg qhs Week 4: placebo 50 mg bid Only one dosage adjustment (increase or decrease), based on efficacy or tolerability, may be made at the investigator's discretion. Subjects must maintain a dose of at least 50 mg/day to remain in the Treatment Period.
Intervention MeSH terms: Topiramate; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Migraine; Chronic Migraine; Cognitive Efficiency; Pilot Study; Long Term Effect

Summary:

      The purpose of this study is to evaluate sustained tolerability, quality of life, and change
      in cognitive efficiency following treatment with OnabotulinumtoxinA and daily topiramate vs.
      OnabotulinumtoxinA and daily placebo (Group A vs. Group B).
    

Eligibility criteria:

        Inclusion Criteria:

          1. must be outpatient, male or female, of any race, between 18 and 65 years of age.

          2. if female of child bearing potential must have a negative pregnancy test result at the
             Screening Visit and practice a reliable method of contraception.

             A female is considered of childbearing potential unless she is post-menopausal for at
             least 12 months prior to administration of study drug, without a uterus and/or both
             ovaries or has been surgically sterilized for at least 6 months prior to study drug
             administration.

             Reliable methods of contraception are:

             Complete abstinence from intercourse from 2 weeks prior to administration of the
             investigational product. Throughout the study, and for a time interval (5 days) after
             completion or premature discontinuation from the study. History of bilateral tubal
             ligation Sterilization of male partner; or, Implants of levonorgestrel; or, Injectable
             progestogen, or, Oral contraceptive (combination therapy with ethinyl estradiol plus a
             progestin) with a placebo week every 1-3 months; or, Any intrauterine device (IUD)
             with published data showing that the highest expected failure rate is less than 1% per
             year (not all IUD's meet this criterion) in use at least 30 days prior to study drug
             administration; or, Spermicide plus a mechanical barrier (e.g., spermicide plus a male
             condom or a female diaphragm); or, Any other barrier methods (only is used in
             combination with any of the above acceptable methods) in use at least 14 days prior to
             study drug administration; or, Any other methods with published data showing that the
             highest expected failure rate for that method is less than 1% per year.

          3. must have history of chronic migraine (with or without aura) according to the criteria
             proposed by the Headache Classification Committee of the International Headache
             Society (IHS) for at least 3 months prior to enrollment.

          4. must be able to understand the requirements of the study including maintaining a
             headache Diary, and signing informed consent.

          5. must be in good general health as determined by investigator.

          6. if taking migraine preventive, must be on a stable dose of preventive medication for
             at least 6 weeks prior to screening.

          7. must have daily access to internet for completion of online daily headache diary.

        Exclusion Criteria:

          1. if female, is pregnant, planning to become pregnant during the study period, are
             breast feeding, or are of childbearing potential and not practicing a reliable form of
             birth control.

          2. has headache disorders outside IHS-defined chronic migraine definition.

          3. has evidence of underlying pathology contributing to their headaches.

          4. has any medical condition that may increase their risk with exposure to
             OnabotulinumtoxinA including diagnosed myasthenia gravis, Eaton-Lambert syndrome,
             amyotrophic lateral sclerosis, or any other significant disease that might interfere
             with neuromuscular function.

          5. has profound atrophy or weakness of muscles in the target areas of injection.

          6. has skin conditions or infections at any injection site.

          7. has allergy or sensitivities to any component of the test medication.

          8. has previously received onabotulinumtoxinA for migraine prevention.

          9. has previously received topiramate.

         10. who in the opinion of the investigator, has active major psychiatric or depressive
             disorders including alcohol/drug abuse.

         11. meets International Headache Society criteria for Medication Overuse Headache with
             opioid or butalbital containing products.

         12. who in the opinion of the investigator, is taking opioid or butalbital containing
             products more than once a week that could be contributing to a pattern of increased
             headaches or cognitive decline.

         13. is planning or requiring surgery during the study.

         14. has a history of poor compliance with medical treatment.

         15. is currently participating in an investigational drug study or has participated in an
             investigational drug study within the previous 30 days of the screening visit.