NINDS CRC Chronic Migraine Treatment Trial (CMTT)

This study has been completed.
Sponsor:
Collaborators:
Ortho-McNeil Janssen Scientific Affairs, LLC
Information provided by (Responsible Party):
Anne Lindblad, The EMMES Corporation
ClinicalTrials.gov Identifier:
NCT00772031
First received: October 14, 2008
Last updated: January 20, 2012
Last verified: January 2012
  Purpose

The purpose of this study is to compare the reduction in the number of severe headache days at six months in people with chronic migraine treated with topiramate and propranolol versus those treated with topiramate and a placebo.


Condition Intervention Phase
Chronic Migraine
Drug: propranolol LA
Drug: topiramate
Drug: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: NINDS Clinical Research Collaboration Chronic Migraine Treatment Trial

Resource links provided by NLM:


Further study details as provided by The EMMES Corporation:

Primary Outcome Measures:
  • Change in the Number of Moderate to Severe Headache Days Within a 28 Day Average Period in Six Months Compared to Baseline [ Time Frame: Baseline (pre-randomization), months 5 and 6 post randomization ] [ Designated as safety issue: No ]
    (Number of moderate to severe headache days (as defined by the International Headache Society Guidelines (2006)) counted over a 28 day diary period at baseline (before treatment with propranolol or placebo)) minus (the number of moderate to severe headache days counted over a 56 day diary period (weeks 16-24 post treatment) divided by 2).


Secondary Outcome Measures:
  • Number of Subjects Experiencing at Least a 30% Reduction in 28-day Moderate to Severe Headache Days [ Time Frame: 6 months post randomization ] [ Designated as safety issue: No ]
  • Number of Subjects Experiencing at Least a 50% Reduction in 28-day Moderate to Severe Headache Days [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Change From Baseline in Beck's Depression Inventory FastScreen Score at 6 Months [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: Yes ]
    Total score from Beck's Depression Inventory FastScreen at 6 months minus total score from Beck's Depression Inventory FastScreen at baseline. Scale scores range from 0 to 21 with higher values indicating worsening depression. the following categories separate participants into groups of depression levels: Minimal (Score 0-3), Mild (Score 4-8),Moderate (Score 9-12),Severe (Score 13-21).

  • Change From Baseline in Migraine Disability Assessment (MIDAS) Score at 6 Months [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
    MIDAS scoring ranges from 0 to 270. The scores are divided into ranges of disability with higher scores indicating increased disability as follows: 0-5 (Grade I - Minimal or infrequent disability); 6-10 (Grade II - Mild or infrequent disability); 11-20 (Grade III - Moderate disability); and 21+ (Grade IV - Severe disability).

  • Change From Baseline in Migraine Specific Quality of Life (MSQ)-Role Restrictive Score at 6 Months [ Time Frame: baseline and 6 months post randomization ] [ Designated as safety issue: No ]
    The MSQ (version 2.1 copyrighted 1992, 1996, 1998 by Glaxo Wellcome Inc., Research Triangle Park, North Carolina) is a 14 item questionnaire. Item responses are summed and scored as a total score and three domains: Role Preventive, Role Restrictive, Emotional Function. Scores within each domain are rescaled to range from 0 to 100. A lower score indicates a poorer quality of life associated with that domain or in total. Because of the observed interaction within a domain, only domain scores were used as outcome measures for this study.

  • Change From Baseline in Migraine-Specific Quality of Life (MSQ)-Role Preventive at 6 Months [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
    The MSQ (version 2.1 copyrighted 1992, 1996, 1998 by Glaxo Wellcome Inc., Research Triangle Park, North Carolina) is a 14 item questionnaire. Item responses are summed and scored as a total score and three domains: Role Preventive, Role Restrictive, Emotional Function. Scores within each domain are rescaled to range from 0 to 100. A lower score indicates a poorer quality of life associated with that domain or in total. Because of the observed interaction within a domain, only domain scores were used as outcome measures for this study.

  • Change From Baseline in Migraine-Specific Quality of Life (MSQ) - Emotional Function at 6 Months [ Time Frame: Baseline and 6 Months ] [ Designated as safety issue: No ]
    The MSQ (version 2.1 copyrighted 1992, 1996, 1998 by Glaxo Wellcome Inc., Research Triangle Park, North Carolina) is a 14 item questionnaire. Item responses are summed and scored as a total score and three domains: Role Preventive, Role Restrictive, Emotional Function. Scores within each domain are rescaled to range from 0 to 100. A lower score indicates a poorer quality of life associated with that domain or in total. Because of the observed interaction within a domain, only domain scores were used as outcome measures for this study.


Enrollment: 191
Study Start Date: October 2008
Study Completion Date: September 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Participants will receive propranolol and topiramate.
Drug: propranolol LA
Propranolol LA up to 240 mg/day
Other Name: Inderal LA
Drug: topiramate
Topiramate is an effective, safe and generally well-tolerated drug used for treating chronic migraine. It is becoming the standard treatment among headache specialists.
Placebo Comparator: 2
Participants will receive a placebo and topiramate.
Drug: topiramate
Topiramate is an effective, safe and generally well-tolerated drug used for treating chronic migraine. It is becoming the standard treatment among headache specialists.
Drug: placebo
an inactive substance

Detailed Description:

Chronic migraine affects about 2 percent of all adults. Currently there are no effective preventative treatments to deal with this disabling condition. Three randomized, placebo-controlled trials found that topiramate was an effective, safe and generally well-tolerated drug for treating chronic migraine. As a result of these trials, topiramate is becoming the standard treatment among headache specialists. Experts agree that treatment with combinations of preventive agents is required in the majority of individuals with chronic migraine for maximal headache relief. No randomized trials have assessed the value of frequently used combinations of preventive agents for chronic migraine.

The goal of this trial is to determine if adding a second drug to topiramate treatment will further reduce the headache burden for people with this condition. In the study, 250 participants with chronic migraine will be randomized to two groups - treatment with topiramate and propranolol or topiramate and placebo. Participants will be followed for six months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • History of chronic migraine for at least 6 months
  • Age ≥ 18 years and age of migraine onset 60 or younger
  • EKG performed in the last 12 months

Exclusion Criteria:

  • Prior neuro-imaging suggesting secondary structural causes of headache
  • Beck Depression Inventory FastScreen score of 13 or greater or other severe psychiatric disorder
  • Contraindication to or prior intolerance of topiramate or propranolol (no history of sinus bradycardia, heart block, heart failure, diabetes prone to hypoglycemia, asthma, kidney stones)
  • History of kidney failure or nephrolithiasis
  • A female who is currently pregnant or lactating or planning to become pregnant in the next year, or is of child-bearing potential and not practicing an acceptable form of birth control
  • Currently requires butalbital or opioid drugs for acute headache treatment 10 or more days a month
  • Failure of prior trials with at least 50 mg of topiramate combined with at least 80 mg of propranolol
  • Use of other migraine preventive drugs (Medications graded as groups 1, 2, 3, and 4 in the AAN Evidence-based Guideline: valproate, divalproex sodium, gabapentin, amitriptyline, nortriptyline, protriptyline, beta-blocker, calcium channel blocker, cyproheptadine; and tizanidine) within the last two months or has received botulinum toxin injection in the past 3 months
  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: NCT00772031

  Show 39 Study Locations
Sponsors and Collaborators
Anne Lindblad
Ortho-McNeil Janssen Scientific Affairs, LLC
Investigators
Principal Investigator: David Dodick, MD Professor of Neurology, Mayo Clinic
Principal Investigator: Stephen D. Silberstein, MD Professor of Neurology, Thomas Jefferson University
Principal Investigator: Deborah Hirtz, MD National Institute of Neurological Disorders and Stroke (NINDS)
  More Information

No publications provided

Responsible Party: Anne Lindblad, Executive Vice President, The EMMES Corporation, The EMMES Corporation
ClinicalTrials.gov Identifier: NCT00772031     History of Changes
Other Study ID Numbers: 08-CRC-01, HHSN265200523641C
Study First Received: October 14, 2008
Results First Received: October 18, 2011
Last Updated: January 20, 2012
Health Authority: United States: Federal Government

Keywords provided by The EMMES Corporation:
chronic migraine, migraine prevention, chronic headache

Additional relevant MeSH terms:
Migraine Disorders
Brain Diseases
Central Nervous System Diseases
Headache Disorders
Headache Disorders, Primary
Nervous System Diseases
Propranolol
Topiramate
Adrenergic Agents
Adrenergic Antagonists
Adrenergic beta-Antagonists
Anti-Arrhythmia Agents
Anti-Obesity Agents
Anticonvulsants
Antihypertensive Agents
Cardiovascular Agents
Central Nervous System Agents
Molecular Mechanisms of Pharmacological Action
Neuroprotective Agents
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on October 21, 2014