The Effect of Amoxicillin Versus Placebo on Gastrointestinal Motility in Children

NCT ID: NCT01530009

Last Updated: 2022-09-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-31
• Study Completion Date: 2022-01-31

Brief Summary

The goal of this study is to determine whether amoxicillin (AMX) alone has an appreciable effect on upper gastrointestinal motility compared to placebo. In particular, induction of phase III of the interdigestive migrating motor complex (MMC) by AMX will be the primary outcome of the study. MMCs are periodic waves of electrical activity resulting in muscular contractions that pass through the walls of the stomach and intestinal tract during the fasting state. It is characterized by an initial period where there is a minimal electrical activity and muscular contraction (phase I), followed by a gradual increase in the frequency of contractions (phase III) that often leads to a characteristic cluster of contractions (phase III). This cycle occurs only in the fasting state in normal individuals and the frequency of phase III is quite varied, dependent on age and the presence of any underlying abnormalities in gastrointestinal motility. Secondary outcomes will include characteristics of the MMC, patient demographics in responders and non-responders, and the safety profile of AMX at the intervention dose.

Detailed Description

Motility disorders are common in childhood and can present with a variety of symptoms including recurrent vomiting, abdominal pain and distension. They are often the reason for multiple medical visits and can be associated with significantly impaired quality of life in severe cases. There are a limited number of available medications used to improve motility in the stomach and small bowel, which include dopamine-receptor antagonists, serotonergic agents and antibiotics such as erythromycin. Among the latter group, amoxicillin-clavulanate (AMC) has been shown to enhance fasting small intestinal motility in adults and children. The mechanism of action is not currently known though theories include indirect release of an intraluminal mediator such as motilin, or direct interaction of the β-lactam moiety with γ-aminobutyric acid receptors in the myenteric plexus.

AMC is a combination of amoxicillin (AMX) with clavulanic acid (CA), a β-lactamase inhibitor. This modification of the drug results in a broader spectrum of antibacterial activity to include AMX sensitive and β-lactamase-producing strains. Although both AMX and AMC are generally well tolerated, AMX can be associated with fewer adverse effects due to the presence of the CA moiety in AMC. AMC is associated with a higher frequency of nausea, vomiting and transient diarrhea compared to AMX. In a study of outpatient children, patients on AMC have been shown to have an increased risk of antibiotic-associated diarrhea. Drug-related liver injury is also more common in patients taking AMC. Furthermore, it is advisable to use the most narrow spectrum antibiotic that demonstrates clinical efficacy in light of the emergence of β-lactam-β-lactamase inhibitor-resistant bacterial strains accelerated by excess antibiotic use.

AMX has a good safety profile and is frequently prescribed for children by community physicians based on history and physical examination alone. It is the recommended first line treatment in common childhood illnesses such as upper respiratory infections, including ear and sinus infections, and community-acquired pneumonia.

The goal of this study is to determine whether a single dose of AMX has an appreciable effect on upper gastrointestinal motility compared to placebo. In particular, induction of phase III of the interdigestive migrating motor complex (MMC) by AMX will be the primary outcome of the study. MMCs are periodic waves of electrical activity resulting in muscular contractions that pass through the walls of the stomach and intestinal tract during the fasting state. It is characterized by an initial period where there is a minimal electrical activity and muscular contraction (phase I), followed by a gradual increase in the frequency of contractions (phase III) that often leads to a characteristic cluster of contractions (phase III). This cycle occurs only in the fasting state in normal individuals and the frequency of phase III is quite varied, dependent on age and the presence of any underlying abnormalities in gastrointestinal motility. Secondary outcomes will include characteristics of the MMC, patient demographics in responders and non-responders, and the safety profile of AMX at the intervention dose.

Conditions

Functional Gastrointestinal Disorders

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Amoxicillin

A liquid preparation of amoxicillin will be administered during the study through a nasoduodenal catheter after random patient assignment.

Group Type: ACTIVE_COMPARATOR

Amoxicillin

Intervention Type: DRUG

A liquid preparation of amoxicillin will be administered via a nasoduodenal catheter as a one time dose of 20 mg/kg.

Placebo

A liquid placebo will be administered via a nasoduodenal catheter to patients based on random assignment.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

A liquid placebo will be administered via nasoduodenal catheter to patients based on random assignment.

Interventions

Amoxicillin

A liquid preparation of amoxicillin will be administered via a nasoduodenal catheter as a one time dose of 20 mg/kg.

Intervention Type: DRUG

Placebo

A liquid placebo will be administered via nasoduodenal catheter to patients based on random assignment.

Intervention Type: OTHER

Other Intervention Names

Amoxil; Amoxicot; DisperMox; Moxilin; Trimox; Moxatag

Eligibility Criteria

Inclusion Criteria

• Children aged 3-21 years referred to the Motility Department at Nationwide Children's Hospital for antroduodenal manometry testing

Exclusion Criteria

• History of allergic reaction to amoxicillin, amoxicillin-clavulanate, or cephalosporins with a common-side chain (e.g. cefadroxil, cefprozil, cefatrizine)
• Therapy with a prokinetic within 3 days of the scheduled antroduodenal manometry
• Families who do not agree to participate

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nationwide Children's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Carlo Di Lorenzo

Pediatric Gastroenterologist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Carlo Di Lorenzo, MD

Role: PRINCIPAL_INVESTIGATOR

Nationwide Children's Hospital

Locations

Nationwide Children's Hospital

Columbus, Ohio, United States

Countries

United States

Other Identifiers

IRB11-00740

Identifier Type: -

Identifier Source: org_study_id