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Valproic Acid and Dihydroergotamine as Abortive Therapy in Pediatric Migraine

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03885154
Recruitment Status : Recruiting
First Posted : March 21, 2019
Last Update Posted : March 27, 2020
Sponsor:
Information provided by (Responsible Party):
Kimberly S Jones, University of Kentucky

Brief Summary:
The objective of this study is to compare clinical efficacy and tolerability of valproic acid (VPA) therapy versus dihydroergotamine (DHE) as abortive therapy in pediatric migraine.

Condition or disease Intervention/treatment Phase
Migraine in Children Drug: Valproic Acid (VPA) Drug: Dihydroergotamine (DHE) Phase 2

Detailed Description:

The purpose of this study is to compare valproic acid (VPA) and dihydroergotamine (DHE) alone and sequentially in the treatment of pediatric migraines.

Inpatient pediatric migraine patients (based on International Classification of Headache Disorders, ICHD-II criteria) or those admitted to the University of Kentucky emergency department will receive standard of care acute headache management as per AAP/AAN guidelines. Those who fail to respond will be considered for further eligibility. Informed consent/assent will be obtained from the patients, parents or legal guardian.

Baseline labs will be collected prior to the start of the study.

  1. Complete Blood Count (CBC)
  2. Comprehensive Metabolic Panel (CMP)
  3. Prothrombin Time/Activated Partial Thromboplastin Time/International Normalized Ratio (PT/APTT/INR)
  4. Magnesium and phosphorous

Patients will initially be randomized into two groups (VPA or DHE) and treated for 24 hours. Those patients whose migraines resolve will end the study at 24 hours. Patients who are refractory to treatment will switch interventions and continue treatment for an additional 24 hours.

Intervention 1: VPA Intervention 2: DHE

Patients in Group 1 will be treated with VPA for 24 hours. They will be given an initial dose of IV VPA at 20mg/kg, followed by continuous infusion of 1mg/kg/hour for 24 hours. Serum levels of VPA will be checked at 4 and 24 hours; depending on drug levels they may also be checked at 8 and 12 hours. The target serum concentration is 100 (+/-10) ug/mL.

Patients in Group 2 will be treated with DHE for 24 hours. Dosing will be weight-based with no single dose >1mg and total 24 hour dose <3mg.

0 hour: 0.5 x (wt in kg) x (0.014) =Xmg 8 hour: 0.75 x (wt in kg) x (0.014) =Xmg 24 hour: 1.0 x (wt in kg) x (0.014) =Xmg

Patients will be assessed for migraine severity at baseline, 4, 8, 12, and 24 hours.

  1. pain (using the standard 0-10 point VAS pain scale)
  2. presence or absence of photophobia
  3. presence or absence of phonophobia
  4. presence or absence of nausea

The endpoint criterion is successful migraine resolution (improvement in VAS and resolution of photophobia, phonophobia, and nausea). Patients meeting this criterion will not continue forward in the study.

At 24 hours, those patients that are refractory to treatment will cross over to the alternate intervention, i.e. patients receiving VPA first will then get DHE, and patients receiving DHE first will then get VPA. Outcomes will be measured for the next 24 hour period as described above.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Valproic Acid and Dihydroergotamine as Abortive Therapy in Pediatric Migraine: An Open-Label Randomized Trial.
Actual Study Start Date : October 3, 2017
Estimated Primary Completion Date : May 2022
Estimated Study Completion Date : May 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Migraine

Arm Intervention/treatment
Active Comparator: Valproic Acid
An initial dose of Valproic Acid (VPA) will be given IV at 20mg/kg, followed by continuous infusion of 1mg/kg/hour for 24 hours. Serum levels of VPA will be checked at 4 and 24 hours, with additional timepoints possible at 8 and 12 hours based on drug levels.
Drug: Valproic Acid (VPA)
IV VPA load 20mg/kg, followed by continuous infusion of 1mg/kg/hr for 24 hours
Other Name: Depakene

Active Comparator: Dihydroergotamine
Dihydroergotamine (DHE) will be given as weight-based dosing, with no single dose >1mg and not exceeding 3mg over 24 hours.
Drug: Dihydroergotamine (DHE)
0 hour: 0.50 x (wt in kg) x (0.014) =Xmg 8 hour: 0.75 x (wt in kg) x (0.014) =Xmg 24 hour: 1.00 x (wt in kg) x (0.014) =Xmg

Active Comparator: Cross-Over to Dihydroergotamine
An initial dose of Valproic Acid (VPA) will be given IV at 20mg/kg, followed by continuous infusion of 1mg/kg/hour for 24 hours. Serum levels of VPA will be checked at 4 and 24 hours, with additional timepoints possible at 8 and 12 hours based on drug levels. Patients who do not respond to VPA after 24 hours will be given Dihydroergotamine (DHE) for the next 24 hours. Dihydroergotamine (DHE) will be given as weight-based dosing, with no single dose >1mg and not exceeding 3mg over 24 hours.
Drug: Valproic Acid (VPA)
IV VPA load 20mg/kg, followed by continuous infusion of 1mg/kg/hr for 24 hours
Other Name: Depakene

Drug: Dihydroergotamine (DHE)
0 hour: 0.50 x (wt in kg) x (0.014) =Xmg 8 hour: 0.75 x (wt in kg) x (0.014) =Xmg 24 hour: 1.00 x (wt in kg) x (0.014) =Xmg

Active Comparator: Cross-Over to Valproic Acid
Dihydroergotamine (DHE) will be given as weight-based dosing, with no single dose >1mg and not exceeding 3mg over 24 hours. Patients who do not respond to DHE after 24 hours will be given Valproic Acid (VPA) for the next 24 hours. An initial dose of Valproic Acid (VPA) will be given IV at 20mg/kg, followed by continuous infusion of 1mg/kg/hour for 24 hours. Serum levels of VPA will be checked at 4 and 24 hours, with additional timepoints possible at 8 and 12 hours based on drug levels.
Drug: Valproic Acid (VPA)
IV VPA load 20mg/kg, followed by continuous infusion of 1mg/kg/hr for 24 hours
Other Name: Depakene

Drug: Dihydroergotamine (DHE)
0 hour: 0.50 x (wt in kg) x (0.014) =Xmg 8 hour: 0.75 x (wt in kg) x (0.014) =Xmg 24 hour: 1.00 x (wt in kg) x (0.014) =Xmg




Primary Outcome Measures :
  1. Change in Pain Perception [ Time Frame: Baseline, 4, 8, 12 and 24 hours ]
    Change in pain perception measured by the 10-point visual analogue scale (VAS), where 0 is "no pain" and 10 is "pain as bad as it could be."


Secondary Outcome Measures :
  1. Presence of photophobia [ Time Frame: Baseline, 4, 8, 12 and 24 hours ]
    Presence of absence of photophobia

  2. Presence of phonophobia [ Time Frame: Baseline, 4, 8, 12 and 24 hours ]
    Presence of absence of phonophobia

  3. Presence of nausea [ Time Frame: Baseline, 4, 8, 12 and 24 hours ]
    Presence or absence of nausea



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   10 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • acute migraine as per ICHD-II criteria
  • pediatric (age 10-18)

Exclusion Criteria:

For Valproic Acid (VPA)

  • Pregnancy
  • Liver disease (Acute or Chronic)
  • Urea Cycle Disorder
  • Mitochondrial Disease

For Dihydroergotamine (DHE)

  • Pregnancy
  • Peripheral vascular disease, coronary heart disease
  • History of cerebrovascular event
  • Severe or poorly controlled hypertension
  • Impaired liver or renal function
  • Triptan given in last 24 hours
  • Hemiplegic migraine

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): NCT03885154


Contacts
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Contact: Sharoon Qaiser, MBBS 859-218-5011 sharoon.qaiser@uky.edu
Contact: Kimberly S Jones, MD 859-218-5011 kimberly.jones@uky.edu

Locations
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United States, Kentucky
University of Kentucky Recruiting
Lexington, Kentucky, United States, 40536
Sponsors and Collaborators
Kimberly S Jones

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Responsible Party: Kimberly S Jones, Assistant Professor of Neurology and Pediatrics, University of Kentucky
ClinicalTrials.gov Identifier: NCT03885154    
Other Study ID Numbers: 44243
First Posted: March 21, 2019    Key Record Dates
Last Update Posted: March 27, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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 Kimberly S Jones, University of Kentucky:
Migraine
Headache
Valproic acid
Dihydroergotamine
Pediatric
Additional relevant MeSH terms:
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Migraine Disorders
Headache Disorders, Primary
Headache Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Dihydroergotamine
Valproic Acid
Anticonvulsants
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
GABA Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Vasoconstrictor Agents
Dopamine Agonists
Dopamine Agents
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents