Acetaminophen and Ibuprofen With and Without Magnesium and Primary Migraine in Childhood

• ClinicalTrials.gov Identifier: NCT01756209
• Recruitment Status: Completed
• First Posted: December 25, 2012
• Results First Posted: March 25, 2020
• Last Update Posted: March 25, 2020
• Sponsor: University of Catanzaro
• Information provided by (Responsible Party): Luca Gallelli, University of Catanzaro

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Migraine	Drug: Magnesium 400Mg; Drug: Ibuprofen 10 mg/kg; Drug: acetaminophen 15 mg/kg	Phase 4

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).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 160 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Primary Purpose: Treatment
• Official Title: The Effects of Acetaminophen and Ibuprofen With and Without Magnesium in the Treatment of Primary Migraine in Childhood
• Study Start Date: January 2010
• Actual Primary Completion Date: February 2012
• Actual Study Completion Date: February 2012

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Acetaminophen; Acetaminophen 15 mg/kg oral single dose (n=40)	Drug: acetaminophen 15 mg/kg; Acetaminophen 15 mg/kg oral single dose; Other Name: acetaminophen
Active Comparator: Ibuprofen; Ibuprofen 10 mg/kg oral single dose (n=40)	Drug: Ibuprofen 10 mg/kg; ibuprofen 10 mg/kg oral single dose; Other Name: ibuprofen
Experimental: Acetaminophen + magnesium 400 mg; Acetaminophen 15 mg/kg oral single dose (n=40) + magnesium 400 mg	Drug: Magnesium 400Mg; magnesium 400 mg + conventional treatment; Other Name: magnesium; Drug: acetaminophen 15 mg/kg; Acetaminophen 15 mg/kg oral single dose; Other Name: acetaminophen
Experimental: ibuprofen + magnesium 400 mg; ibuprofen 10 mg/kg oral single dose (n=40) + magnesium 400 mg	Drug: Magnesium 400Mg; magnesium 400 mg + conventional treatment; Other Name: magnesium; Drug: Ibuprofen 10 mg/kg; ibuprofen 10 mg/kg oral single dose; Other Name: ibuprofen

Outcome Measures

Primary Outcome Measures :

1. Pain-relief [ Time Frame: 3 and 18 months ]

   The primary endpoint was when pain-relief took place and pain intensity differences from baseline (0 hour) to 3 hours after drug treatment. This measurement was defined as the AUC for the sum of the 2 measurements (pain relief and pain intensity difference) at each time point from 0 to 3 hours.

   Pain was measured using the vas analogue scale (range 0-10, where 0 = no pain (score 0) and 100 mm = worst pain (score 10)

Eligibility Criteria

• Ages Eligible for Study: 5 Years to 18 Years (Child, Adult)
• Sexes Eligible for Study: All
• Gender Based Eligibility: Yes
• Gender Eligibility Description: In each group, children were assigned in accordance to age and gender in order to obtain similar groups of treatment.
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

Italy

Pugliese Ciaccio Hospital

Catanzaro, Italy, 88100

Sponsors and Collaborators

University of Catanzaro

Investigators

• Principal Investigator: Francesco Peltrone, MD; Pugliese Ciaccio Hospital

More Information

Additional Information:

• Responsible Party: Luca Gallelli, MD, PhD, University of Catanzaro
• ClinicalTrials.gov Identifier: NCT01756209
• Other Study ID Numbers: Migraine2010
• First Posted: December 25, 2012
• Results First Posted: March 25, 2020
• Last Update Posted: March 25, 2020
• Last Verified: March 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Additional relevant MeSH terms:

Migraine Disorders; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Acetaminophen; Ibuprofen; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Antipyretics; Anti-Inflammatory Agents, Non-Steroidal; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action