The Childhood and Adolescent Migraine Prevention Study

Migraine Clinical Trial

— CHAMP  

Official title:

Amitriptyline and Topiramate in the Prevention of Childhood Migraine

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01581281
• Other study ID #: CIN-001
• Secondary ID: 1U01NS076788-01
• Status: Terminated
• Phase: Phase 3
• First received: December 16, 2011
• Last updated: September 21, 2016
• Start date: June 2012
• Est. completion date: January 2016

Study information

• Verified date: September 2016
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this research study is to test two medicines for migraine prevention in children and adolescents.

Description:

The purpose of this research study is to test two medicines for migraine prevention in children and adolescents. The investigators want to see if amitriptyline and/or topiramate are better than placebo (sugar pill) in reducing headache frequency in children and adolescents ages 8 to 17 with migraines. At this time, there are no FDA approved medicines approved in the US for the prevention treatment of migraine headaches in children and adolescents.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 488
• Est. completion date: January 2016
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 8 Years to 17 Years

Eligibility

Inclusion Criteria:

• Migraine with or without aura (International Classification of Headache Disorders, 2nd Edition (ICHD-II) or chronic migraine (ICHD-II revised)

• Migraine frequency based upon prospective headache diary of 28 days must be = 4. Migraine frequency defined as any migraine during one day in the 28 day baseline period (1)

• PedMIDAS Disability Score > 10, indicating at least mild disruption in daily activities and < 140, indicating extreme disability that may require more comprehensive, multi-component therapy

• Females or males 8-17 years, inclusive

1. Migraine frequency is defined as the period from the onset to the stop time of painful migraine symptoms not to exceed 24 hours with the clock starting at midnight. If painful symptoms last longer than 24 hours, this is considered a new and distinct migraine headache. If painful symptoms recur within 24 hours of initial onset, this is considered part of the initial migraine episode and would be counted as one migraine.

Exclusion Criteria:

• Continuous migraine defined as an unrelenting headache for a 28 day period

• Weight less than 30 kg or greater than 120 kg

• Unwilling to avoid taking non-specific acute medication such as NSAIDS (e.g., ibuprofen), more than 3 times per week, or migraine specific acute medications such as triptans more than 6 times per month

• Currently taking other prophylactic anti-migraine medication within a period equivalent to 2 weeks of that medication before entering the screening phase, or the use of Botulinum toxin (Botox®) within 3 months of entering the screening phase

• Subjects who have previously failed an adequate trial of AMI or TPM for prophylaxis of at least 3 months duration at doses recommended for migraine relief because of lack of efficacy or adverse events(2)

• Current use of disallowed medications/products: opioids, antipsychotics, antimanics, barbiturates, benzodiazepines, muscle relaxants, sedatives, tramadol, nutraceuticals, SSRIs, or SSNRIs

• Known history of allergic reaction or anaphylaxis to AMI or TPM

• Abnormal findings on ECG at baseline, particularly lengthening of the QT interval greater than or equal to 450 msec

• Subject is pregnant or has a positive pregnancy test

• Subject is sexually active and not using a medically acceptable form of contraception

• Diagnosis of epilepsy or other neurological diseases

• History of kidney stones

• Inability to swallow pills after using behavioral techniques if indicated between screening visit and baseline visit (3)

• Present psychiatric disease as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM IV) (e.g. psychosis, bipolar disorder, major depression, generalized anxiety disorder), alcohol or drug dependence, or documented developmental delays or impairments (e.g., autism, cerebral palsy, or mental retardation) that, in the opinion of the site investigator, would interfere with adherence to study requirements or safe participation in the trial

• Any and all other diagnoses or conditions which in the opinion of the site investigator, that would prevent the patient from being a suitable candidate for the study or interfere with the medical care needs of the study subject

(2)"Previously failed an adequate trial of AMI or TPM" is defined as: dosage of 1mg/kg/day of AMI or 2 mg/kg/day of TPM; trial of at least 3 months duration; efficacy of having at least a 50% decrease in migraine frequency in response to drug therapy; or unable to tolerate taking the medication due to treatment-related side effects.

(3)Subjects who cannot swallow pills at the time of the screening visit will be given a training session using behavioral techniques. Upon return for baseline visit, if the subject continues to be unable to swallow pills, the subject will be excluded from the study.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Headache
• Migraine
• Migraine Disorders

Intervention

Drug:
• Amitriptyline
Amitriptyline will be administered twice daily at home during the 8-week titration period followed by a 16 week maintenance phase of the highest tolerated dose. The morning dose is a placebo pill. Dosing of amitriptyline will be weight-based.
• Topiramate
Topiramate will be administered twice daily at home during the 8-week titration period followed by a 16 week maintenance phase of the highest tolerated dose. Dosing of topiramate will be weight-based.
• Placebo
Placebo will be administered twice daily at home during the 8-week titration period followed by a 16 week maintenance period.

Locations

Country	Name	City	State
United States	Akron Children's Hospital	Akron	Ohio
United States	Dent Neurological Institute	Amherst	New York
United States	Atlanta Headache Specialists	Atlanta	Georgia
United States	Children's Hospital Colorado	Aurora	Colorado
United States	University of Maryland School of Medicine	Baltimore	Maryland
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	The Children's Hospital, Cleveland Clinic	Cleveland	Ohio
United States	Colorado Springs Neurological Associates	Colorado Springs	Colorado
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Dallas Pediatric Neurology Associates	Dallas	Texas
United States	Josephson Wallack Munshower Neurology Research	Indianapolis	Indiana
United States	Children's Mercy Hospital	Kansas City	Kansas
United States	University of Louisville Health Sciences Center	Louisville	Kentucky
United States	Marshfield Clinic	Marshfield	Wisconsin
United States	LeBonheur Children's Hospital	Memphis	Tennessee
United States	Winthrop University Hospital	Mineola	New York
United States	The Headache Institute at Roosevelt Hospital	New York	New York
United States	Eastern Virginia Medical School	Norfolk	Virginia
United States	Oklahoma Health Sciences	Oklahoma City	Oklahoma
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Phoenix Children's Medical Group	Phoenix	Arizona
United States	Preferred Clinical Research	Pittsburgh	Pennsylvania
United States	University of Nevada	Reno	Nevada
United States	Mayo Clinic	Rochester	Minnesota
United States	Primary Children's Medical Center	Salt Lake City	Utah
United States	University of California-San Francisco Headache Center	San Francisco	California
United States	Schenectady Neurological Constultants, PC	Schenectady	New York
United States	Seattle Children's Hospital	Seattle	Washington
United States	Saint Louis University	St. Louis	Missouri
United States	Stanford Hospital and Clinics	Stanford	California
United States	Scott and White Healthcare	Temple	Texas
United States	Children's Hospital of Boston	Waltham	Massachusetts
United States	Children's National Medical Center	Washington DC	District of Columbia
United States	Premiere Research Institute	West Palm Beach	Florida
United States	New England Regional Headache Center	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati	National Institute of Neurological Disorders and Stroke (NINDS)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reduction in Headache Frequency, defined as = 50% reduction in headache days.	Determine if amitriptyline and/or topiramate are superior to placebo in a percentage of subjects with a 50% or greater reduction in headache days (defined as the number of days with headache for a given 4 week period) in children and adolescents. Conduct a comparative effectiveness study of the two therapies with respect to reducing headache frequency (defined as the number of days with headache for a given 4 week period).	4 week baseline period and last 4 weeks of the 24-week trial	No
Secondary	There are four secondary outcomes. Secondary Outcome #1: Reduction in absolute headache disability score on PedMIDAS.	This outcome compares absolute headache disability score (measured by PedMIDAS) for: Amitriptyline vs. Placebo; Topiramate vs. Placebo; Amitriptyline vs. Topiramate	4 week baseline period and last 4 weeks of the 24-week trial	No
Secondary	Secondary Outcome #2: Reduction in number of headache days.	Compare absolute headache days per 28 day period, measured by the change in absolute headache days for: Amitriptyline vs. placebo; Topiramate vs. placebo; Amitriptyline vs. Topiramate	4 week baseline period and last 4 weeks of the 24-week trial	No
Secondary	Secondary Outcome #3: Tolerability of amitriptyline and topiramate.	Determine if amitriptyline and/or topiramate are well tolerated.; Tolerability will be defined as the percentage of randomized patients that completed the 24-week treatment phase. All three study groups will be compared.	4 week baseline period and last 4 weeks of the 24-week trial	Yes
Secondary	Secondary Outcome #4: Occurrence of treatment-emergent serious adverse events.	To determine if amitriptyline or topiramate differ from placebo on the occurrence of treatment-emergent serious adverse events.	4 week baseline period to last 4 weeks of the 24-week trial	Yes
Secondary	Safety evaluation is an additional component of the trial that will be assessed.	Safety will be measured by the quantitative review of adverse events for all three arms of the study in comparison with placebo and the adverse events profiles reported in the package inserts for the study drugs.	4 week baseline period to last 4 weeks of the 24-week trial	Yes