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Distinct Mechanisms of Cognitive Behavioral Therapy Effects in Youth With Migraine

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ClinicalTrials.gov Identifier: NCT03472092
Recruitment Status : Not yet recruiting
First Posted : March 21, 2018
Last Update Posted : March 27, 2018
Sponsor:
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati

Brief Summary:
This study evaluates whether cognitive behavioral therapy (CBT) is more effective in engaging and changing brain mechanisms associated with predicting a reduction in headaches than pill based therapies (placebo or amitriptyline).

Condition or disease Intervention/treatment Phase
Headache, Migraine Migraine Migraine Disorders Headache Behavioral: Cognitive Behavioral Therapy (CBT) Drug: Placebo Drug: Amitriptyline Phase 2

Detailed Description:

Pediatric migraine is a prevalent disorder that results in significant pain and disability for children and adolescents. Little is known about the distinct brain changes that occur in youth with migraine when they receive cognitive behavioral therapy, which is known to decrease headache days for these patients. Pediatric medical and behavioral clinicians can use mechanistic insights from this study to provide patients and families with a stronger rationale for treatment, thereby decreasing stigma and increasing confidence in and commitment to the care plan.

This project will study migraine, which affects > 6 million youth in the U.S. Cochrane reviews show that psychological therapies for pediatric headache result in better outcomes than control conditions (56% improved vs. 22% in 714 participants), and our CBT+Amitriptyline Study found that 66% of youth with chronic migraine had a ≥ 50% reduction in headache days compared to 36% in an education control+Amitriptyline (AMI) group. Despite this evidence base, the neural mechanisms supporting the efficacy of CBT for pain remain poorly understood. The lack of mechanistic understanding is a barrier to treatment utilization, particularly given the time, effort, and expense for pediatric migraine patients to receive CBT vs. conventional pharmacological therapy (which in a national trial reduced headache days similar to placebo pill: AMI 52% of participants improved; Placebo 61%). Pilot data from the investigators demonstrate that: CBT induces changes in brain connectivity/activation, and QST at baseline predicts reduced migraines at 8 weeks.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 240 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Mechanistic trial examining brain changes and conditioned pain modulation changes in youth with migraine treated with either cognitive behavioral therapy, placebo, or amitriptyline.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description: Cognitive behavioral therapy assignment is known to the treating therapist/care provider. Placebo and amitriptyline are double blinded.
Primary Purpose: Basic Science
Official Title: Distinct Mechanisms of Cognitive Behavioral Therapy Effects in Youth With Migraine: Insights From Neuroimaging and Quantitative Sensory Testing (The How and Why Youth With Headaches Get Better)
Estimated Study Start Date : September 2018
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : March 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Headache Migraine

Arm Intervention/treatment
Experimental: Cognitive Behavioral Therapy (CBT)
Cognitive Behavioral Therapy (CBT) is a psychological coping skills training using education on gate control theory of pain, behavioral strategies such as muscle relaxation and activity pacing, and cognitive strategies including distraction, problem solving, and using calming self-statements.
Behavioral: Cognitive Behavioral Therapy (CBT)
This intervention will consist of 8 weekly sessions. The duration of each session is about 45 minutes and will be led by a psychologist/therapist using a manualized protocol. About half of the sessions will be conducted in person and the remaining sessions will be offered via telehealth (Skype or phone).
Other Names:
  • CBT
  • coping skills
  • mind body relaxation

Placebo Comparator: Placebo
The placebo pill will be administered once a day at home, to be taken by mouth.
Drug: Placebo
The placebo pill will be administered once a day at home for 8 weeks, to be taken by mouth with or without food under the supervision of the participant's parent or guardian. To maintain blinding, all participants will receive 1 matching capsule as a daily dose to be taken each evening during the study.
Other Name: Placebo Oral Capsule

Active Comparator: Amitriptyline
Amitriptyline will be administered once a day at home, to be taken by mouth. Dosage will be weight-based.
Drug: Amitriptyline
Amitriptyline will be administered once a day at home for 8 weeks, to be taken by mouth with or without food under the supervision of the participant's parent or guardian. To maintain blinding, all participants will receive 1 matching capsule as a daily dose to be taken each evening during the study. For this study, a dose of 0.25 mg/kg/day will be provided for the 1st 2 weeks, followed by a dose of 0.5 mg/kg/day for 2 weeks, 0.75 mg/kg/day for 2 weeks and a maximum dose of 1.0 mg/kg/day for 2 weeks based on tolerability. Participants experiencing tolerability issues, may be held a current dose rather than titrated to the next dosage if deemed appropriate by the study doctor.




Primary Outcome Measures :
  1. Change in functional resonance imaging (fMRI) [ Time Frame: baseline and post treatment (8 weeks post randomization) ]
    For each participant, changes in distinct neural mechanisms of the brain will be compared to between baseline and post treatment (8 weeks). For each participant, the primary endpoint will be examine changes in brain connectivity and activation.


Secondary Outcome Measures :
  1. Change in pain modulation [ Time Frame: baseline and post treatment (8 weeks post randomization) ]
    For each participant, changes in the efficiency of pain modulation using a quantitative sensory testing paradigm will be assessed. This outcome will compare between baseline and post treatment (8 weeks).



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Ages Eligible for Study:   10 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis: Migraine with or without aura or chronic migraine that meets the International Classification of Headache Disorders, 3rd Edition (beta) (ICHD-3b) criteria
  • Frequency: Headache frequency based upon prospective headache diary of 28 days must be ≥ 8 and ≤ 28
  • PedMIDAS: 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
  • English speaking: able to complete interviews and questionnaires in English

Exclusion Criteria:

  • Continuous migraine defined as an unrelenting headache for a 28 day period
  • Weight less than 30 kg or greater than 120 kg, or weight/size incompatible with MRI scanner
  • Must agree not to take 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
  • No current prophylactic anti-migraine medication within a period equivalent to < 5 half-lives of that medication before entering the screening phase, and agree to not begin a migraine prevention medication during the study period
  • Current use of the following medications/products: opioids, antipsychotics, antimanics, barbiturates, benzodiazepines, muscle relaxants, sedatives, tramadol, nutraceuticals
  • Known history of allergic reaction or anaphylaxis to amitriptyline
  • Abnormal findings on ECG at baseline, particularly lengthening of the QT interval ≥ 450 msec
  • Orthodontic braces, metallic or electronic implants, or other metal objects in the body which obscure or interfere with the MRI, or pose a risk from heating, movement, or malfunction in the MRI environment
  • Claustrophobia
  • Youth who are pregnant, or those who are sexually active and not using a medically accepted form of contraception (barrier or hormonal methods)
  • Diagnosis of epilepsy or other neurological diseases
  • Inability to learn how to swallow pills using behavioral techniques (if indicated)
  • Present psychiatric disease as defined by 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, ADHD, or mental retardation) that, in the opinion of the investigator, would interfere with adherence to study requirements or safe participation in the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03472092


Contacts
Contact: LeighAnn Chamberlin, MEd 513-636-9739 leighann.chamberlin@cchmc.org

Locations
United States, Ohio
Cincinnati Children's Hospital Medical Center Not yet recruiting
Cincinnati, Ohio, United States, 45229
Contact: LeighAnn Chamberlin, MEd    513-939-9739    leighann.chamberlin@cchmc.org   
Principal Investigator: Scott Powers, PhD         
Principal Investigator: Robert Coghill, PhD         
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
Principal Investigator: Scott Powers, PhD Children's Hospital Medical Center, Cincinnati
Principal Investigator: Robert Coghill, PhD Children's Hospital Medical Center, Cincinnati

Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT03472092     History of Changes
Other Study ID Numbers: CIN0101-CAP Imaging Study
First Posted: March 21, 2018    Key Record Dates
Last Update Posted: March 27, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Children's Hospital Medical Center, Cincinnati:
headache
migraine
cognitive behavioral therapy
amitriptyline
functional magnetic resonance imaging
conditioned pain modulation
brain connectivity
pediatrics

Additional relevant MeSH terms:
Migraine Disorders
Headache
Headache Disorders, Primary
Headache Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Pain
Neurologic Manifestations
Signs and Symptoms
Amitriptyline
Amitriptyline, perphenazine drug combination
Antidepressive Agents, Tricyclic
Antidepressive Agents
Psychotropic Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Adrenergic Agents
Neurotransmitter Agents
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants