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NINDS CRC Chronic Migraine Treatment Trial (CMTT)

Primary Purpose

Chronic Migraine

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
propranolol LA
topiramate
placebo
Sponsored by
Anne Lindblad
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Chronic Migraine focused on measuring chronic migraine, migraine prevention, chronic headache

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Mayo Clinic 5777 E Mayo Blvd
  • Paradigm Clinical, Inc. 1324 W. Prince Rd
  • Dr. Stephen David Forner - 1405 Magnolia Avenue, Suite B
  • Shanti Clinical Trials, 1880 West Washington Street
  • NervPro Research, 15825 Laguna Canyon Road, Suite 202
  • Mercy Medical Group- CHWMF 3000 Q Street, Neurology
  • Health Sciences America, LLC, 1515 N Federal Hwy, Suite 105
  • Southeast Clinical Research, LLC, 304 NE 1st Street
  • Scientific Clinical Research, Inc 1065 NE 125th Street , Ste 417
  • Neurology Associates of Ormond Beach 8 Mirror Lake Drive Suite A&B
  • Neurologique Foundation, Inc. 6 Fairfield Blvd. Suite 11
  • Neurology Clinical Research, Inc, 3540 North Pine Island Rd
  • Dr. B. Abraham, P.C. 3020 Highway 124
  • Ft. Wayne Neurological Center 7956 W. Jefferson Blvd.
  • MidAmerica Neuroscience Research Foundation, 8550 Marshall Dr, Suite 100
  • Trover Health System Center for Clinical Studies, 200 Clinic Drive
  • New England Center for Clinical Research (NECCR), 52 Brigham St #7
  • New England Regional Headache Center, Inc 85 Prescott St, Ste 101
  • ClinSite, LLC 24 Frank Lloyd Wright Drive, Lobby M
  • Anderson & Collins Clinical Research 1 Ethel Road, Suite 106B
  • Dent Neurologic Institute, 3980 Sheridan Drive
  • Montefiore Headache Center 1575 Blondell Avenue Ste 225
  • Island Neurological Associates, PC, 824 Old Country Road
  • Schenectady Neurological Consultants 1401 Union Street
  • Mission Neurology, Research Institute Mission Hospital, 509 Biltmore
  • Guilford Neurologic Associates, 1126 North Church Street, Suite 200
  • ClinExcel Research 7908 Cincinnati-Dayton Rd, Ste J
  • Abington Neurological Associates, Ltd., 1245 Highland Avenue, Ste 301
  • Neurology and Sleep Medicine PC, 701 Ostrum Street, Suite 302
  • Jefferson Headache Center/Thomas Jefferson Univ. 111 South 11th Street, Suite 8130
  • Progress Clinical Trials, 707 Kings Lane
  • Texas Neurology, PA, 6301 Gaston Avenue, Suite 400 West Tower
  • Houston Headache Clinic, 1213 Hermann Drive, Suite 820
  • Houston Sleep Center, Todd J. Swick, MD, PA, 7500 San Felipe, Suite 525
  • Protenium Clinical Research, LLC 1725 Chadwick Court Suite 200
  • Starlight Clinical Research, 1325 W. South Jordan Pkwy, Ste 101
  • Swedish Pain & Headache Center 101 Madison St, Suite 200
  • West Virginia University 1 Medical Center Dr, Box 9180
  • Gundersen Clinic, Ltd, 1836 South Avenue, MS: EB3-002

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

1

2

Arm Description

Participants will receive propranolol and topiramate.

Participants will receive a placebo and topiramate.

Outcomes

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
(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
Number of Subjects Experiencing at Least a 50% Reduction in 28-day Moderate to Severe Headache Days
Change From Baseline in Beck's Depression Inventory FastScreen Score at 6 Months
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
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
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
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
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.

Full Information

First Posted
October 14, 2008
Last Updated
January 20, 2012
Sponsor
Anne Lindblad
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS), Ortho-McNeil Janssen Scientific Affairs, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT00772031
Brief Title
NINDS CRC Chronic Migraine Treatment Trial
Acronym
CMTT
Official Title
NINDS Clinical Research Collaboration Chronic Migraine Treatment Trial
Study Type
Interventional

2. Study Status

Record Verification Date
January 2012
Overall Recruitment Status
Completed
Study Start Date
October 2008 (undefined)
Primary Completion Date
September 2010 (Actual)
Study Completion Date
September 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Anne Lindblad
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS), Ortho-McNeil Janssen Scientific Affairs, LLC

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Migraine
Keywords
chronic migraine, migraine prevention, chronic headache

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
191 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Active Comparator
Arm Description
Participants will receive propranolol and topiramate.
Arm Title
2
Arm Type
Placebo Comparator
Arm Description
Participants will receive a placebo and topiramate.
Intervention Type
Drug
Intervention Name(s)
propranolol LA
Other Intervention Name(s)
Inderal LA
Intervention Description
Propranolol LA up to 240 mg/day
Intervention Type
Drug
Intervention Name(s)
topiramate
Intervention Description
Topiramate is an effective, safe and generally well-tolerated drug used for treating chronic migraine. It is becoming the standard treatment among headache specialists.
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
an inactive substance
Primary Outcome Measure Information:
Title
Change in the Number of Moderate to Severe Headache Days Within a 28 Day Average Period in Six Months Compared to Baseline
Description
(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).
Time Frame
Baseline (pre-randomization), months 5 and 6 post randomization
Secondary Outcome Measure Information:
Title
Number of Subjects Experiencing at Least a 30% Reduction in 28-day Moderate to Severe Headache Days
Time Frame
6 months post randomization
Title
Number of Subjects Experiencing at Least a 50% Reduction in 28-day Moderate to Severe Headache Days
Time Frame
6 months
Title
Change From Baseline in Beck's Depression Inventory FastScreen Score at 6 Months
Description
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).
Time Frame
Baseline and 6 months
Title
Change From Baseline in Migraine Disability Assessment (MIDAS) Score at 6 Months
Description
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).
Time Frame
Baseline and 6 months
Title
Change From Baseline in Migraine Specific Quality of Life (MSQ)-Role Restrictive Score at 6 Months
Description
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.
Time Frame
baseline and 6 months post randomization
Title
Change From Baseline in Migraine-Specific Quality of Life (MSQ)-Role Preventive at 6 Months
Description
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.
Time Frame
Baseline and 6 months
Title
Change From Baseline in Migraine-Specific Quality of Life (MSQ) - Emotional Function at 6 Months
Description
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.
Time Frame
Baseline and 6 Months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Dodick, MD
Organizational Affiliation
Professor of Neurology, Mayo Clinic
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Stephen D. Silberstein, MD
Organizational Affiliation
Professor of Neurology, Thomas Jefferson University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Deborah Hirtz, MD
Organizational Affiliation
National Institute of Neurological Disorders and Stroke (NINDS)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic 5777 E Mayo Blvd
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Facility Name
Paradigm Clinical, Inc. 1324 W. Prince Rd
City
Tuscon
State/Province
Arizona
ZIP/Postal Code
85705
Country
United States
Facility Name
Dr. Stephen David Forner - 1405 Magnolia Avenue, Suite B
City
Chico
State/Province
California
ZIP/Postal Code
95926
Country
United States
Facility Name
Shanti Clinical Trials, 1880 West Washington Street
City
Colton
State/Province
California
ZIP/Postal Code
92324
Country
United States
Facility Name
NervPro Research, 15825 Laguna Canyon Road, Suite 202
City
Irvine
State/Province
California
ZIP/Postal Code
92618
Country
United States
Facility Name
Mercy Medical Group- CHWMF 3000 Q Street, Neurology
City
Sacramento
State/Province
California
ZIP/Postal Code
95816
Country
United States
Facility Name
Health Sciences America, LLC, 1515 N Federal Hwy, Suite 105
City
Boca Raton
State/Province
Florida
ZIP/Postal Code
33432
Country
United States
Facility Name
Southeast Clinical Research, LLC, 304 NE 1st Street
City
Chiefland
State/Province
Florida
ZIP/Postal Code
32626
Country
United States
Facility Name
Scientific Clinical Research, Inc 1065 NE 125th Street , Ste 417
City
Miami
State/Province
Florida
ZIP/Postal Code
33161
Country
United States
Facility Name
Neurology Associates of Ormond Beach 8 Mirror Lake Drive Suite A&B
City
Ormond Beach
State/Province
Florida
ZIP/Postal Code
32174
Country
United States
Facility Name
Neurologique Foundation, Inc. 6 Fairfield Blvd. Suite 11
City
Ponte Vedra
State/Province
Florida
ZIP/Postal Code
32082
Country
United States
Facility Name
Neurology Clinical Research, Inc, 3540 North Pine Island Rd
City
Sunrise
State/Province
Florida
ZIP/Postal Code
33351
Country
United States
Facility Name
Dr. B. Abraham, P.C. 3020 Highway 124
City
Snellville
State/Province
Georgia
ZIP/Postal Code
30039
Country
United States
Facility Name
Ft. Wayne Neurological Center 7956 W. Jefferson Blvd.
City
Ft. Wayne
State/Province
Indiana
ZIP/Postal Code
46804
Country
United States
Facility Name
MidAmerica Neuroscience Research Foundation, 8550 Marshall Dr, Suite 100
City
Lenexa
State/Province
Kansas
ZIP/Postal Code
66214
Country
United States
Facility Name
Trover Health System Center for Clinical Studies, 200 Clinic Drive
City
Madisonville
State/Province
Kentucky
ZIP/Postal Code
42431
Country
United States
Facility Name
New England Center for Clinical Research (NECCR), 52 Brigham St #7
City
New Bedford
State/Province
Massachusetts
ZIP/Postal Code
02740
Country
United States
Facility Name
New England Regional Headache Center, Inc 85 Prescott St, Ste 101
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01605-2982
Country
United States
Facility Name
ClinSite, LLC 24 Frank Lloyd Wright Drive, Lobby M
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48106
Country
United States
Facility Name
Anderson & Collins Clinical Research 1 Ethel Road, Suite 106B
City
Edison
State/Province
New Jersey
ZIP/Postal Code
08817
Country
United States
Facility Name
Dent Neurologic Institute, 3980 Sheridan Drive
City
Amherst
State/Province
New York
ZIP/Postal Code
14226
Country
United States
Facility Name
Montefiore Headache Center 1575 Blondell Avenue Ste 225
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
Island Neurological Associates, PC, 824 Old Country Road
City
Plainview
State/Province
New York
ZIP/Postal Code
11803
Country
United States
Facility Name
Schenectady Neurological Consultants 1401 Union Street
City
Schenectady
State/Province
New York
ZIP/Postal Code
12308
Country
United States
Facility Name
Mission Neurology, Research Institute Mission Hospital, 509 Biltmore
City
Asheville
State/Province
North Carolina
ZIP/Postal Code
28801
Country
United States
Facility Name
Guilford Neurologic Associates, 1126 North Church Street, Suite 200
City
Greensboro
State/Province
North Carolina
ZIP/Postal Code
27401
Country
United States
Facility Name
ClinExcel Research 7908 Cincinnati-Dayton Rd, Ste J
City
West Chester
State/Province
Ohio
ZIP/Postal Code
45069
Country
United States
Facility Name
Abington Neurological Associates, Ltd., 1245 Highland Avenue, Ste 301
City
Abington
State/Province
Pennsylvania
ZIP/Postal Code
19001
Country
United States
Facility Name
Neurology and Sleep Medicine PC, 701 Ostrum Street, Suite 302
City
Bethlehem
State/Province
Pennsylvania
ZIP/Postal Code
18015
Country
United States
Facility Name
Jefferson Headache Center/Thomas Jefferson Univ. 111 South 11th Street, Suite 8130
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Progress Clinical Trials, 707 Kings Lane
City
Tullahoma
State/Province
Tennessee
ZIP/Postal Code
37388
Country
United States
Facility Name
Texas Neurology, PA, 6301 Gaston Avenue, Suite 400 West Tower
City
Dallas
State/Province
Texas
ZIP/Postal Code
75214
Country
United States
Facility Name
Houston Headache Clinic, 1213 Hermann Drive, Suite 820
City
Houston
State/Province
Texas
ZIP/Postal Code
77004
Country
United States
Facility Name
Houston Sleep Center, Todd J. Swick, MD, PA, 7500 San Felipe, Suite 525
City
Houston
State/Province
Texas
ZIP/Postal Code
77063
Country
United States
Facility Name
Protenium Clinical Research, LLC 1725 Chadwick Court Suite 200
City
Hurst
State/Province
Texas
ZIP/Postal Code
76054
Country
United States
Facility Name
Starlight Clinical Research, 1325 W. South Jordan Pkwy, Ste 101
City
South Jordan
State/Province
Utah
ZIP/Postal Code
84095
Country
United States
Facility Name
Swedish Pain & Headache Center 101 Madison St, Suite 200
City
Seattle
State/Province
Washington
ZIP/Postal Code
98116
Country
United States
Facility Name
West Virginia University 1 Medical Center Dr, Box 9180
City
Morgantown
State/Province
West Virginia
ZIP/Postal Code
26506 - 9180
Country
United States
Facility Name
Gundersen Clinic, Ltd, 1836 South Avenue, MS: EB3-002
City
La Crosse
State/Province
Wisconsin
ZIP/Postal Code
54601
Country
United States

12. IPD Sharing Statement

Learn more about this trial

NINDS CRC Chronic Migraine Treatment Trial

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