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A Study to Evaluate the Tolerability of Botox and Topiramate or Botox and Placebo and Effect on Cognitive Efficiency

This study has been completed.
Sponsor:
Collaborator:
Allergan
Information provided by (Responsible Party):
Cady, Roger, M.D.
ClinicalTrials.gov Identifier:
NCT01700387
First received: October 1, 2012
Last updated: October 10, 2014
Last verified: October 2014
  Purpose

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).


Condition Intervention Phase
Chronic Migraine
Drug: onabotulinumtoxinA
Drug: Topiramate
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Pilot Study to Evaluate the Tolerability of OnabotulinumtoxinA Plus Topiramate vs. OnabotulinumtoxinA Plus Placebo and Long Term Effect of Treatment on Cognitive Efficiency and Continuation of Care

Resource links provided by NLM:


Further study details as provided by Cady, Roger, M.D.:

Primary Outcome Measures:
  • Subject Attrition Post Randomization [ Time Frame: Collected on Visit 2 (Day 29) through Visit 6 (Day 365) ] [ Designated as safety issue: No ]
    Count of subject attrition following randomization and reason for attrition (Consent withdrawn, Withdrawn due to adverse event, Lost to follow up)

  • Subject Global Impression of Change (SGIC) [ Time Frame: Collected on Visit 3 (Day 113), Visit 4 (Day 197), Visit 5 (281), and Visit 6 (Day 365) ] [ Designated as safety issue: No ]
    Score on Subject Global Impression of Change at Visits 3-6 (Day 113 and 365). Likert scale ranging from 1-7, where 1 = extremely worse and 7 = extremely better.

  • Physician Global Impression of Change (PGIC) [ Time Frame: Collected on Visit 3 (Day 113), Visit 4 (Day 197), Visit 5 (281), and Visit 6 (Day 365) ] [ Designated as safety issue: No ]
    Score on Physician Global Impression of Change at Visits 3-6 (Day 113 and 365). Likert scale ranging from 1-7, where 1 = extremely worse and 7 = extremely better.

  • Subject's Mental Efficiency Workload Test (MEWT) Overall Performance Index (PI) Score at Visits 2-6 to Measure Cognitive Efficiency [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
  • Subject's Controlled Oral Word Association Test (COWAT) Scores at Visits 2-6 to Measure Cognitive Efficiency [ Time Frame: 12 Months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in Number of Headache Days Reported in 30-day Baseline Period vs. Treatment Period Months 1-12 [ Time Frame: 13 Months ] [ Designated as safety issue: No ]
  • Subject's Headache Impact Test (HIT-6) Scores at Visits 2-6 to Measure Effect of Headache in Subject's Life [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
  • MEWT Score for Simple Reaction Time Sub-test at Visits 2-6 to Measure Mental Efficiency [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
  • MEWT Score for Running Memory Continuous Performance Task Sub-test at Visits 2-6 to Measure Mental Efficiency [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
  • MEWT Scores for Matching to Sample Sub-test at Visit 2-6 to Measure Mental Efficiency [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
  • MEWT Scores for Mathematical Processing Sub-test at Visits 2-6 to Measure Mental Efficiency [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
  • Subject Estimation of Compliance With Daily Topiramate [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
  • Pharmacoeconomic Estimates on Number of Patients Needed to Treat (Randomize) to Have One Successful Patient at 3, 6, 9, and 12 Months. [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
  • Number of Participants With Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 13 Months ] [ Designated as safety issue: No ]
  • Subject's Migraine Specific Quality of Life Questionnaire (MSQ) Scores at Baseline, 3, 6, 9 and 12 Months to Measure Subject's Quality of Life [ Time Frame: 12 Months ] [ Designated as safety issue: No ]

Enrollment: 20
Study Start Date: October 2012
Study Completion Date: August 2014
Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: OnabotulinumtoxinA + Topiramate

Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with topiramate. During the first month of the treatment period, subjects will titrate as follows:

Week 1: topiramate 25 mg q hs Week 2: topiramate 25 mg bid Week 3: topiramate 25 mg q am + topiramate 50mg q hs Week 4: topiramate 50mg 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.

Drug: onabotulinumtoxinA
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.
Other Name: Botox, Botulinum Toxin Type A Purified Neurotoxin Complex
Drug: Topiramate

Subjects randomized to the onabotulinumtoxinA + topiramate group will receive:

Week 1: topiramate 25 mg q hs Week 2: topiramate 25 mg bid Week 3: topiramate 25 mg q am + topiramate 50mg q hs Week 4: topiramate 50mg 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.

Other Name: Topamax
Placebo Comparator: OnabotulinumtoxinA + Placebo

Subject will receive 155 U onabotulinumtoxinA injections at 31 sites every 3 months for 12 months and treat daily with placebo. During the first month of the treatment period, subjects will titrate as follows:

Week 1: 1 tab q hs Week 2: 1 tab bid Week 3: 1 tab q am + 2 tabs q hs Week 4: 2 tabs bid

Drug: onabotulinumtoxinA
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.
Other Name: Botox, Botulinum Toxin Type A Purified Neurotoxin Complex
Drug: Placebo

Subjects randomized to the onabotulinumtoxinA + placebo group will receive:

Week 1: placebo 25 mg q hs Week 2: placebo 25 mg bid Week 3: topiramate 25 mg q am + topiramate 50mg q hs Week 4: topiramate 50mg 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.


  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01700387

Locations
United States, Missouri
Clinvest/A Division of Banyan Group, Inc.
Springfield, Missouri, United States, 65807
Sponsors and Collaborators
Cady, Roger, M.D.
Allergan
Investigators
Principal Investigator: Roger K Cady, MD Clinvest/A Division of Banyan Group, Inc.
  More Information

Additional Information:
Publications:
Responsible Party: Cady, Roger, M.D.
ClinicalTrials.gov Identifier: NCT01700387     History of Changes
Other Study ID Numbers: 12-001AL, 71403
Study First Received: October 1, 2012
Results First Received: October 7, 2014
Last Updated: October 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Cady, Roger, M.D.:
Migraine
Chronic Migraine
Cognitive Efficiency
Pilot Study
Long Term Effect

Additional relevant MeSH terms:
Botulinum Toxins
Botulinum Toxins, Type A
Topiramate
Anti-Dyskinesia Agents
Anti-Obesity Agents
Anticonvulsants
Central Nervous System Agents
Neuromuscular Agents
Neuroprotective Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014