Effect of Azithromycin on Oesophageal Hypomotility
Primary Purpose
Esophageal Motility Disorders
Status
Completed
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
Azithromycin
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Esophageal Motility Disorders
Eligibility Criteria
Inclusion Criteria:
Healthy subjects:
- Written ICF signed voluntarily before the first trial-related activity.
- Subjects male and female within age range of 18-70 years old (extremes included)
- BMI <35
Patients group:
- Written ICF signed voluntarily before the first trial-related activity.
- Patients male and female, aged 18-70
- Been diagnosed with severe oesophageal hypomotility based on Chicago classification 2011
- Must have moderate or severe reflux symptoms and/ or dysphagia, with at least one of these symptoms of moderate severity or worse, and at a minimum average frequency of three days a week during the two weeks prior to the study date
If the subject is a woman of childbearing potential, she
- must have a negative urine pregnancy test before the start of treatment (minimum β-Human Chorionic Gonadotropin [HCG] sensitivity of 25 mIU/ml), and
- must agree to either use an effective form of birth control (i.e., stabilized on oral contraceptives for at least 1 month or using implanted, transdermal or injected contraceptive hormones, an intra-uterine device, or continuous abstinence from heterosexual sexual contact), or a combination of a barrier method and a spermicidal agent (i.e., cervical cap and spermicidal agent, condom and spermicidal agent, or diaphragm and spermicidal agent),
Exclusion Criteria:
Healthy subjects:
- Any incidental abnormal oesophageal motility finding
- History of gastrointestinal symptoms, gastrointestinal tract surgery or other recent abdominal operation within last 3 months.
- Major psychiatric, neurological, respiratory, liver, haemorrhagic and cardiac disorders, malignancies
- Pregnancy and no wheat allergy
Patients:
- Subjects with a documented history of long segment (>3 cm) Barrett's oesophagus.
- Subjects with documented or suspected large (> 3 cm) hiatus hernia.
- Subjects with fundoplication, endoscopic anti-reflux procedure or major prior GI surgery.
- Subjects with structural abnormalities of oesophagus (ie. Rings and webs, scleroderma)
- Severe oesophageal motility disorders other than oesophageal hypomotility (e.g., achalasia, nutcracker oesophagus).
- Subjects who suffer from frequent vomiting (>1/week)
- Current diagnosis of co-existing psychiatric disease (including alcohol or drug abuse); controlled depression and anxiety are allowed, when treated with at most
- Allergy to prokinetic medicine (AZI), gluten or egg, allergy to latex (reflux monitoring catheter has cross reaction with latex)
- Patients with concomitant prohibited medications, unless willing or able to withdraw from these medications
- Use of prohibited co-medication less than 7 days before the start of the study
- Any condition that, in the opinion of the Investigator, would complicate or compromise the trial (e.g., human immunodeficiency virus [HIV] infection, gastroduodenal ulcer) or the well-being of the subject, or evidence of any clinically relevant pathology that could interfere with trial results or put subject safety at risk.
- Participation in an investigational drug trial in 30 days prior to enrolment.
- Pregnant or breast-feeding subjects.
Sites / Locations
- Royal London Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Active Comparator
Arm Label
Placebo
AZI
Arm Description
Taking placebo 3 times per week for four weeks
Outcomes
Primary Outcome Measures
Effect of Azithromycin on oesophageal peristalstic contraction amplitude in patients with hypomotility
The amplitude of peristaltic contractions and also Distal Contractal Integral which summarises the vigour of peristalsis will be measured before and after treatment with Azithromycin. Measurement is performed by oesophageal high resolution manometry. The measures will be compared to decide on the effect oo Azithromycin on oesophageal motility.
Secondary Outcome Measures
Manometric oesophageal body response (amplitude of peristaltic contractions in mmHg and also Distal Contractal Integral in mmHg.cm.second) to solid bolus swallows, MRS and outlet obstruction in healthy subjects and patients with oesophageal hypomotility.
The above parameters will be measured before and after treatment with Azithromycin. Measurement is performed by oesophageal high resolution manometry. The measures will be compared to decide on the effect oo Azithromycin on oesophageal motility.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01448993
Brief Title
Effect of Azithromycin on Oesophageal Hypomotility
Official Title
Effect Of Azithromycin On Oesophageal Function In Patients With Dysphagia Or Gastro-Oesophageal Reflux Associated With Frequent Oesophageal Hypomotility
Study Type
Interventional
2. Study Status
Record Verification Date
April 2015
Overall Recruitment Status
Completed
Study Start Date
August 2012 (undefined)
Primary Completion Date
January 2015 (Actual)
Study Completion Date
January 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
JAFAR JAFARI
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Patients with difficulty in swallowing (dysphagia) or with reflux disease are frequently found to suffer from oesophageal hypomotility (weak contractions).
Oesophageal motility is currently measured using high-resolution manometry (HRM). This technique has a 36 pressure sensors on a plastic tube to record the pressure in side the oesophagus.
Several pharmaceutical agents (prokinetics) can stimulate oesophageal motility. However, use of prokinetics in patients with oesophageal hypomotility led to disappointing results. An explanation for these disappointing results is that inappropriate patients were targeted. The appropriate patient would be the one who still have some viable muscle in the oesophagus that can respond to pharmacological stimuli.
In the process of developing treatment strategies in patients with oesophageal hypomotility, testing the preserved capacity of oesophageal muscles could be useful to predict the response of these patients to prokinetic drugs. The following tests have the potential to reveal the preserved capacity of the oesophageal muscle to respond to stronger/medicinal stimuli.
- Multiple rapid swallowing (MRS) of 5ml water boluses stimulates oesophagus. A normal response to MRS requires on the one hand integrity of neural mechanisms and on the other hand a functional oesophageal muscle.
- External abdominal compression can increase the resistance to bolus transport via oesophagus. The normal oesophagus produces contractions of higher amplitude and duration in order to maintain a normal bolus transit.
- Swallowing bread boluses require stronger oesophageal contractions for a successful bolus transit.
The purpose of the proposed project is to firstly assess the effect of Azithromycin on oesophageal hypomotility and secondly to evaluate the predictive values of the stimulation techniques in predicting the likelihood the positive response to drug therapy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Esophageal Motility Disorders
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
26 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Taking placebo 3 times per week for four weeks
Arm Title
AZI
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Azithromycin
Intervention Description
Taking 250mg azithromycin 3 times per week in alternate days.
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Effect of Azithromycin on oesophageal peristalstic contraction amplitude in patients with hypomotility
Description
The amplitude of peristaltic contractions and also Distal Contractal Integral which summarises the vigour of peristalsis will be measured before and after treatment with Azithromycin. Measurement is performed by oesophageal high resolution manometry. The measures will be compared to decide on the effect oo Azithromycin on oesophageal motility.
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
Manometric oesophageal body response (amplitude of peristaltic contractions in mmHg and also Distal Contractal Integral in mmHg.cm.second) to solid bolus swallows, MRS and outlet obstruction in healthy subjects and patients with oesophageal hypomotility.
Description
The above parameters will be measured before and after treatment with Azithromycin. Measurement is performed by oesophageal high resolution manometry. The measures will be compared to decide on the effect oo Azithromycin on oesophageal motility.
Time Frame
4 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Healthy subjects:
Written ICF signed voluntarily before the first trial-related activity.
Subjects male and female within age range of 18-70 years old (extremes included)
BMI <35
Patients group:
Written ICF signed voluntarily before the first trial-related activity.
Patients male and female, aged 18-70
Been diagnosed with severe oesophageal hypomotility based on Chicago classification 2011
Must have moderate or severe reflux symptoms and/ or dysphagia, with at least one of these symptoms of moderate severity or worse, and at a minimum average frequency of three days a week during the two weeks prior to the study date
If the subject is a woman of childbearing potential, she
must have a negative urine pregnancy test before the start of treatment (minimum β-Human Chorionic Gonadotropin [HCG] sensitivity of 25 mIU/ml), and
must agree to either use an effective form of birth control (i.e., stabilized on oral contraceptives for at least 1 month or using implanted, transdermal or injected contraceptive hormones, an intra-uterine device, or continuous abstinence from heterosexual sexual contact), or a combination of a barrier method and a spermicidal agent (i.e., cervical cap and spermicidal agent, condom and spermicidal agent, or diaphragm and spermicidal agent),
Exclusion Criteria:
Healthy subjects:
Any incidental abnormal oesophageal motility finding
History of gastrointestinal symptoms, gastrointestinal tract surgery or other recent abdominal operation within last 3 months.
Major psychiatric, neurological, respiratory, liver, haemorrhagic and cardiac disorders, malignancies
Pregnancy and no wheat allergy
Patients:
Subjects with a documented history of long segment (>3 cm) Barrett's oesophagus.
Subjects with documented or suspected large (> 3 cm) hiatus hernia.
Subjects with fundoplication, endoscopic anti-reflux procedure or major prior GI surgery.
Subjects with structural abnormalities of oesophagus (ie. Rings and webs, scleroderma)
Severe oesophageal motility disorders other than oesophageal hypomotility (e.g., achalasia, nutcracker oesophagus).
Subjects who suffer from frequent vomiting (>1/week)
Current diagnosis of co-existing psychiatric disease (including alcohol or drug abuse); controlled depression and anxiety are allowed, when treated with at most
Allergy to prokinetic medicine (AZI), gluten or egg, allergy to latex (reflux monitoring catheter has cross reaction with latex)
Patients with concomitant prohibited medications, unless willing or able to withdraw from these medications
Use of prohibited co-medication less than 7 days before the start of the study
Any condition that, in the opinion of the Investigator, would complicate or compromise the trial (e.g., human immunodeficiency virus [HIV] infection, gastroduodenal ulcer) or the well-being of the subject, or evidence of any clinically relevant pathology that could interfere with trial results or put subject safety at risk.
Participation in an investigational drug trial in 30 days prior to enrolment.
Pregnant or breast-feeding subjects.
Facility Information:
Facility Name
Royal London Hospital
City
London
ZIP/Postal Code
E1 1BB
Country
United Kingdom
12. IPD Sharing Statement
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Effect of Azithromycin on Oesophageal Hypomotility
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