The Effect of Amoxicillin Versus Placebo on Gastrointestinal Motility in Children
Condition: Functional Gastrointestinal Disorders
MeSH terms: Gastrointestinal Diseases; Digestive System Diseases
Study type: Interventional

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.
    

Intervention name(s): Amoxicillin; Placebo
Intervention type(s): Drug; Other
Intervention description(s): A liquid preparation of amoxicillin will be administered via a nasoduodenal catheter as a one time dose of 20 mg/kg.; A liquid placebo will be administered via nasoduodenal catheter to patients based on random assignment.
Other intervention name(s): Amoxil; Amoxicot; DisperMox; Moxilin; Trimox; Moxatag
Intervention MeSH terms: Amoxicillin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Antroduodenal manometry; Child; Adolescent; Amoxicillin; Gastrointestinal Motility