Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT01530009 |
| Other study ID # |
IRB11-00740 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
January 2012 |
| Est. completion date |
January 2022 |
Study information
| Verified date |
September 2022 |
| Source |
Nationwide Children's Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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.
