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

NCT01700387 | Completed Phase 4 Results DMC

• 2 other identifiers: 12-001AL71403
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Chronic Migraine

Keywords

Migraine; Chronic Migraine; Cognitive Efficiency; Pilot Study; Long Term Effect

Outcome Measures

Primary Outcomes (4)

• Subject Attrition Post Randomization

  Count of subject attrition following randomization and reason for attrition (Consent withdrawn, Withdrawn due to adverse event, Lost to follow up)

  Collected on Visit 2 (Day 29) through Visit 6 (Day 365)

• Subject Global Impression of Change (SGIC)

  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.

  Collected on Visit 3 (Day 113), Visit 4 (Day 197), Visit 5 (281), and Visit 6 (Day 365)

• Physician Global Impression of Change (PGIC)

  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.

  Collected on Visit 3 (Day 113), Visit 4 (Day 197), Visit 5 (281), and Visit 6 (Day 365)

• Subject's Controlled Oral Word Association Test (COWAT) Score Percent Change Compared From Baseline to Visits 3-6

  The Controlled Oral Word Association Test (COWAT) is a measure of verbal fluency. Raw COWAT scores have a lower bound of 0 with no upper bound. Higher scores indicate better verbal fluency. COWAT score percent change from baseline will be reported. Positive change scores represent better verbal fluency compared to baseline.

  Baseline, Visit 3 (Day 113) through Visit 6 (Day 365)

Secondary Outcomes (9)

• Number of Headache Days

  Baseline and Months 1-12

• Headache Impact Test (HIT-6) Scores at Visits 2-6 to Measure Effect of Headache in Subject's Life

  Collected on Visit 2 (Day 29), 3 (Day 113), Visit 4 (Day 197), Visit 5 (281), and Visit 6 (Day 365)

• MEWT Simple Reaction Time Sub-test Score Percent Change Compared From Baseline to Visits 3-6

  Baseline, Visit 3 (Day 113), Visit 4 (Day 197), Visit 5 (281), and Visit 6 (Day 365)

• MEWT Running Memory Continuous Performance Task Sub-test Score Percent Change Compared From Baseline to Visits 3-6

  Baseline, Visit 3 (Day 113), Visit 4 (Day 197), Visit 5 (281), and Visit 6 (Day 365)

• MEWT Matching to Sample Sub-test Score Percent Change Compared From Baseline to Visits 3-6

  Baseline, Visit 3 (Day 113), Visit 4 (Day 197), Visit 5 (281), and Visit 6 (Day 365)

Study Arms (2)

OnabotulinumtoxinA + Topiramate

EXPERIMENTAL

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 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.

Drug: onabotulinumtoxinA; Drug: Topiramate

OnabotulinumtoxinA + Placebo

PLACEBO COMPARATOR

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

Drug: onabotulinumtoxinA; Drug: Placebo

Interventions

onabotulinumtoxinA DRUG

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.

Also known as: Botox, Botulinum Toxin Type A Purified Neurotoxin Complex

OnabotulinumtoxinA + Placebo; OnabotulinumtoxinA + Topiramate

Topiramate DRUG

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.

Also known as: Topamax

OnabotulinumtoxinA + Topiramate

Placebo DRUG

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.

OnabotulinumtoxinA + Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• must be outpatient, male or female, of any race, between 18 and 65 years of age.
• 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.
• 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.
• must be able to understand the requirements of the study including maintaining a headache Diary, and signing informed consent.
• must be in good general health as determined by investigator.
• if taking migraine preventive, must be on a stable dose of preventive medication for at least 6 weeks prior to screening.
• must have daily access to internet for completion of online daily headache diary.

You may not qualify if:

• 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.
• has headache disorders outside IHS-defined chronic migraine definition.
• has evidence of underlying pathology contributing to their headaches.
• 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.
• has profound atrophy or weakness of muscles in the target areas of injection.
• has skin conditions or infections at any injection site.
• has allergy or sensitivities to any component of the test medication.
• has previously received onabotulinumtoxinA for migraine prevention.
• has previously received topiramate.
• who in the opinion of the investigator, has active major psychiatric or depressive disorders including alcohol/drug abuse.
• meets International Headache Society criteria for Medication Overuse Headache with opioid or butalbital containing products.
• 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.
• is planning or requiring surgery during the study.
• has a history of poor compliance with medical treatment.
• 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.

Sponsors & Collaborators

• Cady, Roger, M.D.: lead
• Allergan: collaborator

Study Sites (1)

Clinvest/A Division of Banyan Group, Inc.

Springfield, Missouri, 65807, United States

Location

Related Publications (3)

• Bootsma HP, Aldenkamp AP, Diepman L, Hulsman J, Lambrechts D, Leenen L, Majoie M, Schellekens A, de Krom M. The Effect of Antiepileptic Drugs on Cognition: Patient Perceived Cognitive Problems of Topiramate versus Levetiracetam in Clinical Practice. Epilepsia. 2006;47 Suppl 2:24-7. doi: 10.1111/j.1528-1167.2006.00683.x.

  PMID: 17105455 RESULT

• Kim SY, Lee HW, Jung DK, Suh CK, Park SP. Cognitive Effects of Low-dose Topiramate Compared with Oxcarbazepine in Epilepsy Patients. J Clin Neurol. 2006 Jun;2(2):126-33. doi: 10.3988/jcn.2006.2.2.126. Epub 2006 Jun 20.

  PMID: 20396496 RESULT

• Meador KJ, Loring DW, Vahle VJ, Ray PG, Werz MA, Fessler AJ, Ogrocki P, Schoenberg MR, Miller JM, Kustra RP. Cognitive and behavioral effects of lamotrigine and topiramate in healthy volunteers. Neurology. 2005 Jun 28;64(12):2108-14. doi: 10.1212/01.WNL.0000165994.46777.BE.

  PMID: 15985582 RESULT

MeSH Terms

Conditions

Migraine Disorders

Interventions

Botulinum Toxins, Type A; Topiramate

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors; Fructose; Hexoses; Monosaccharides; Sugars; Carbohydrates; Ketoses

Results Point of Contact

• Title: Dr. Roger Cady
• Organization: Clinvest/A Division of Banyan Group Inc.

rcady@banyangroupinc.com

417-883-7889

Study Officials

• Roger K Cady, MD

  Clinvest

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDIV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2012
• First Posted: October 4, 2012
• Study Start: October 1, 2012
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: August 18, 2020
• Results First Posted: October 13, 2014

Record last verified: 2020-08

Locations

US (1)