Clinical trial NCT01756209: Acetaminophen and Ibuprofen With and Without Magnesium and Primary Migraine in Childhood
Official title: The Effects of Acetaminophen and Ibuprofen With and Without Magnesium in the Treatment of Primary Migraine in Childhood
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Migraine
Lead sponsor: University of Catanzaro
Sponsor class: OTHER
First posted: 2012-12-25
Enrollment: 160
Sex: ALL
Minimum age (years): 5
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Aim: The purpose of this study was to evaluate both the effects of ibuprofen and/or acetaminophen for the acute treatment of primary migraine in children in or out prophylactic treatment with magnesium.

Methods: The study had been approved by the Researchers Ethics Committee of the "Pugliese-Ciaccio" Hospital (protocol number 720/2010; EUDRACT NUMBER 2012-005737-36) and the children ranging from the ages of 5 to 18 years with at least four attack/month of primary migraine were enrolled. A Visual Analogical Scale was used to evaluate pain intensity at the moment of admission to the study (start of the study) and every month up to 18 months later (end of the study).

Detailed description: Study design The present work is a single-blind, balanced recruitment, parallel-group, single center study in outpatient children enrolled at the Pediatric Unit-Pugliese Ciaccio Hospital in Catanzaro, Italy, between January 2010 and June 2010.

This study had been approved by the Researchers Ethics Committee of the "Pugliese-Ciaccio" Hospital (protocol number 720/2010; EUDRACT NUMBER 2012-005737-36), and was conducted following the Declaration of Helsinki and the Guidelines for Good Clinical Practice criteria.

Population Children with migraine without aura (MoA) of both sexes aged from 5 to 16 years, with at least four attacks /month, were eligible for the study. MoA was diagnosed according to the criteria for pediatric age of the International Classification of Headache Disorders (IHS-2) \[22\].

Exclusion criteria were the following: mental retardation (IQ \<70), genetic syndromes (e.g., Down syndrome, Prader-Willi syndrome, fragile X syndrome), hypothyroidism, psychiatric disorders (i.e.: schizophrenia, mood disorders, ADHD), neuromuscular disorders, epilepsy, obesity (BMI\>95 percentiles), liver or renal diseases, gastrointestinal disorders such as peptic or duodenal ulcer, dyspepsia, or heartburn; hypersensitivity to medication studies.

Informed written consent was obtained by parents.

Experimental protocol In a balanced recruitment study eligible outpatients with primary acute migraine were assigned to receive at pain onset: acetaminophen (15mg/kg) or ibuprofen (10mg/kg). Moreover, in order to evaluate the prophylaxis effect of magnesium in another set of experiments eligible children were assigned to receive a daily magnesium supplement (400 mg/daily) and then one single dose of acetaminophen (15mg/kg) or ibuprofen (10 mg/kg) at the time of pain (Figure 1). In this study, in agreement with the Declaration of Helsinki (1991), we did not use a placebo group.

In each group, children were assigned in accordance to age, gender in order to obtain similar groups of treatment.

In order to assess the intensity of pain, before and up to 3 hours after the administration of both drugs used in the present protocol, a non standardized ad hoc scale and a visual analogical scale (VAS) were used.

Specifically, for the pre-dose assessments, the pain intensity was measured on an arbitrarily established categoric scales in response to the question, "What is your pain level at this time?" with response choices from 0 to 3, where 0 = none; 1 = mild; 2 = moderate; and 3 = severe. In addition, a visual analogical scale (VAS) was used to assess pain severity before, during and after the treatment. Patients were asked to draw a single vertical line on the 100-mm VAS, where 0 = no pain (score 0) and 100 mm = worst pain (score 10). This scale had been previously used to measure pain in pediatric populations .

The safety on medication studies was assessed in terms of frequency and nature of adverse drug reactions (ADRs). In order to evaluate the association between ADRs and drug treatment, the Naranjo Adverse Probability Scale was applied .

Number, duration, severity of pain attacks, analgesic intake and the occurrence of ADRs were recorded in a daily diary card 1 month prior to the trial and subsequently during the entire period of the study. For each patient, follow-up sessions were planned every month after enrollment and continued for 18 months (end of the study).

Eligibility criteria: Inclusion Criteria:

* Children with migraine without aura (MoA) diagnosed according to the criteria for pediatric age of the International Classification of Headache Disorders (IHS-2)
* aged from 5 to 18 years
* at least four attacks /month

Exclusion Criteria:

* mental retardation (IQ \<70)
* genetic syndromes (e.g., Down syndrome, Prader-Willi syndrome, fragile X syndrome)
* hypothyroidism
* psychiatric disorders (i.e.: schizophrenia, mood disorders, ADHD),
* neuromuscular disorders,
* epilepsy,
* obesity (BMI\>95 percentiles),
* liver or renal diseases,
* gastrointestinal disorders such as peptic or duodenal ulcer, dyspepsia, or heartburn;
* hypersensitivity to medication studies.

Primary outcomes:
measure: Pain-relief
timeFrame: 3 and 18 months
Secondary outcomes:
Other outcomes:
Locations:
city: Catanzaro
country: Italy
facility: Pugliese Ciaccio Hospital
Study officials:
affiliation: Pugliese Ciaccio Hospital
name: Francesco Peltrone, MD
role: PRINCIPAL_INVESTIGATOR
References: