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Esophageal Hypersensitivity Study in Patients With Gastroesophageal Reflux Disease (GERD)

Primary Purpose

Sensitivity in Esophagus

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
AZD1386
Placebo to AZD1386
Sponsored by
AstraZeneca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sensitivity in Esophagus focused on measuring GERD, patient, esophagus, pain

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Provision of signed informed consent form
  • BMI 18.5-35.0, inclusive
  • Continuous PPI treatment for GERD during the last 4 weeks

Exclusion Criteria:

  • Patients that have not experienced any GERD symptoms improvement at all after PPI treatment
  • Unstable or clinically significant disorders including cardiovascular, respiratory, renal, hepatic, metabolic, psychiatric, other gastrointestinal and esophageal disorders besides GERD
  • Prior surgery of the upper GI tract

Sites / Locations

  • Research Site
  • Research Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

First AZD1386, then washout, then placebo

First placebo, then washout, then AZD1386

Arm Description

Outcomes

Primary Outcome Measures

Time to Visual Analogue Scale 7 (VAS7) During Thermal Stimulation at 1.5 Hours Post-Dose.
A probe (bag) was inserted 7cm above the lower esophageal sphincter (LES). Heat stimuli were applied by recirculation of heated water in the bag. Prior to recirculation the bag is filled with 7mL to ensure adequate mucosal contact. Water was heated up to a maximum of 63° C and the stimulation was continued until VAS 7 was reached. The intensities of the non-painful sensations were scored with the following descriptors added to facilitate the scoring: = vague perception of mild sensation = definite perception of mild sensation = vague perception of moderate sensation = definite perception of moderate sensation For painful sensations the patients will use the scale from 5-10 anchored at: = pain detection = slight pain = moderate pain = medium pain intensity = intense pain = unbearable pain

Secondary Outcome Measures

Time to Visual Analogue Scale 7 (VAS7) During Thermal Stimulation at 0.5 Hours Post Dose
A probe (bag) was inserted 7cm above the lower esophageal sphincter (LES). Heat stimuli were applied by recirculation of heated water in the bag. Prior to recirculation the bag is filled with 7mL to ensure adequate mucosal contact. Water was heated up to a maximum of 63° C and the stimulation was continued until VAS 7 was reached. The intensities of the non-painful sensations were scored with the following descriptors added to facilitate the scoring: = vague perception of mild sensation = definite perception of mild sensation = vague perception of moderate sensation = definite perception of moderate sensation For painful sensations the patients will use the scale from 5-10 anchored at: = pain detection = slight pain = moderate pain = medium pain intensity = intense pain = unbearable pain
Time to Visual Analogue Scale 7 (VAS7) During Thermal Stimulation at 2.5 Hours Post Dose
A probe (bag) was inserted 7cm above the lower esophageal sphincter (LES). Heat stimuli were applied by recirculation of heated water in the bag. Prior to recirculation the bag is filled with 7mL to ensure adequate mucosal contact. Water was heated up to a maximum of 63° C and the stimulation was continued until VAS 7 was reached. The intensities of the non-painful sensations were scored with the following descriptors added to facilitate the scoring: = vague perception of mild sensation = definite perception of mild sensation = vague perception of moderate sensation = definite perception of moderate sensation For painful sensations the patients will use the scale from 5-10 anchored at: = pain detection = slight pain = moderate pain = medium pain intensity = intense pain = unbearable pain
Volume at Visual Analogue Scale 7 (VAS7) During Mechanical Stimulation at 0.5 Hours Post Dose
A probe (bag) was inserted 7cm above the lower esophageal sphincter (LES). Volume change in the bag was recorded continuously at each level of the visual analogue scale (VAS) and up to VAS7 (Volume at Visual Analogue Scale 7). The intensities of the non-painful sensations were scored with the following descriptors added to facilitate the scoring: = vague perception of mild sensation = definite perception of mild sensation = vague perception of moderate sensation = definite perception of moderate sensation For painful sensations the patients will use the scale from 5-10 anchored at: = pain detection = slight pain = moderate pain = medium pain intensity = intense pain = unbearable pain
Volume at Visual Analogue Scale 7 (VAS7) During Mechanical Stimulation at 1.5 Hours Post-Dose
A probe (bag) was inserted 7cm above the lower esophageal sphincter (LES). Volume change in the bag was recorded continuously at each level of the visual analogue scale (VAS) and up to VAS7 (Volume at Visual Analogue Scale 7). The intensities of the non-painful sensations were scored with the following descriptors added to facilitate the scoring: = vague perception of mild sensation = definite perception of mild sensation = vague perception of moderate sensation = definite perception of moderate sensation For painful sensations the patients will use the scale from 5-10 anchored at: = pain detection = slight pain = moderate pain = medium pain intensity = intense pain = unbearable pain
Volume at Visual Analogue Scale 7 (VAS7) During Mechanical Stimulation at 2.5 Hours Post-Dose.
A probe (bag) was inserted 7cm above the lower esophageal sphincter (LES). Volume change in the bag was recorded continuously at each level of the visual analogue scale (VAS) and up to VAS7 (Volume at Visual Analogue Scale 7). The intensities of the non-painful sensations were scored with the following descriptors added to facilitate the scoring: = vague perception of mild sensation = definite perception of mild sensation = vague perception of moderate sensation = definite perception of moderate sensation For painful sensations the patients will use the scale from 5-10 anchored at: = pain detection = slight pain = moderate pain = medium pain intensity = intense pain = unbearable pain
Current at Visual Analogue Scale 7 (VAS7) During Electrical Stimulation 0.5 Hours Post Dose
A probe (bag) was inserted 7cm above the lower esophageal sphincter (LES) and stimulations were performed at approximately 8 cm above the LES. The intensity of the stimuli is increased steadily in steps of 0.5 to 1 mA and the intensity corresponding to the VAS levels 1, 3, 5 and 7 were recorded. The current will be increased until the patient report moderate pain (VAS 7) or max 80 mA. The intensities of the non-painful sensations were scored with the following descriptors added to facilitate the scoring: = vague perception of mild sensation = definite perception of mild sensation = vague perception of moderate sensation = definite perception of moderate sensation For painful sensations the patients will use the scale from 5-10 anchored at: = pain detection = slight pain = moderate pain = medium pain intensity = intense pain = unbearable pain
Current at Visual Analogue Scale 7 (VAS7) During Electrical Stimulation at 1.5 Hours Post Dose
A probe (bag) was inserted 7cm above the lower esophageal sphincter (LES) and stimulations were performed at approximately 8 cm above the LES. The intensity of the stimuli is increased steadily in steps of 0.5 to 1 mA and the intensity corresponding to the VAS levels 1, 3, 5 and 7 were recorded. The current will be increased until the patient report moderate pain (VAS 7) or max 80 mA. The intensities of the non-painful sensations were scored with the following descriptors added to facilitate the scoring: = vague perception of mild sensation = definite perception of mild sensation = vague perception of moderate sensation = definite perception of moderate sensation For painful sensations the patients will use the scale from 5-10 anchored at: = pain detection = slight pain = moderate pain = medium pain intensity = intense pain = unbearable pain
Current at Visual Analogue Scale 7 (VAS7) During Electrical Stimulation at 2.5 Hours Post Dose
A probe (bag) was inserted 7cm above the lower esophageal sphincter (LES) and stimulations were performed at approximately 8 cm above the LES. The intensity of the stimuli is increased steadily in steps of 0.5 to 1 mA and the intensity corresponding to the VAS levels 1, 3, 5 and 7 were recorded. The current will be increased until the patient report moderate pain (VAS 7) or max 80 mA. The intensities of the non-painful sensations were scored with the following descriptors added to facilitate the scoring: = vague perception of mild sensation = definite perception of mild sensation = vague perception of moderate sensation = definite perception of moderate sensation For painful sensations the patients will use the scale from 5-10 anchored at: = pain detection = slight pain = moderate pain = medium pain intensity = intense pain = unbearable pain
AUCt
Area under the plasma concentration curve from time zero to the last quantifiable concentration
Cmax
Maximum plasma concentration
Tmax
Time of maximum plasma concentration
SBP
Supine Systolic Blood Pressure at 1.5 hours post dose
DBP
Supine Diastolic Blood Pressure at 1.5 hours post dose
Pulse
Supine Pulse at 1.5 hours post dose
QTcF
QT interval corrected for heart rate using Fredericia formula(QTcF) at 1.5 hours post dose
Body Temperature
Oral Body Temperature at 1.5 hours post dose
Clinically Relevant Change of Laboratory Variables
Number of participants with clinically relevant change of laboratory variables(clinical chemistry, haematology and urinalysis parameters)

Full Information

First Posted
November 20, 2009
Last Updated
October 10, 2012
Sponsor
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT01019928
Brief Title
Esophageal Hypersensitivity Study in Patients With Gastroesophageal Reflux Disease (GERD)
Official Title
A Phase IIa, Double-blind, Randomized, 2-way Cross-over Study to Evaluate the Effect of a Single Dose of AZD1386 95 mg Compared to Placebo in a Multimodal Experimental Pain Model on Esophageal Sensitivity in GERD Patients With a Partial Response to PPI Treatment
Study Type
Interventional

2. Study Status

Record Verification Date
October 2012
Overall Recruitment Status
Completed
Study Start Date
November 2009 (undefined)
Primary Completion Date
January 2011 (Actual)
Study Completion Date
January 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of the study is to compare sensitivity of visceral pain in the esophagus using different pain stimuli.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sensitivity in Esophagus
Keywords
GERD, patient, esophagus, pain

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
First AZD1386, then washout, then placebo
Arm Type
Experimental
Arm Title
First placebo, then washout, then AZD1386
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
AZD1386
Intervention Description
95 mg, oral solution, single dose
Intervention Type
Drug
Intervention Name(s)
Placebo to AZD1386
Intervention Description
Placebo, oral solution, single dose
Primary Outcome Measure Information:
Title
Time to Visual Analogue Scale 7 (VAS7) During Thermal Stimulation at 1.5 Hours Post-Dose.
Description
A probe (bag) was inserted 7cm above the lower esophageal sphincter (LES). Heat stimuli were applied by recirculation of heated water in the bag. Prior to recirculation the bag is filled with 7mL to ensure adequate mucosal contact. Water was heated up to a maximum of 63° C and the stimulation was continued until VAS 7 was reached. The intensities of the non-painful sensations were scored with the following descriptors added to facilitate the scoring: = vague perception of mild sensation = definite perception of mild sensation = vague perception of moderate sensation = definite perception of moderate sensation For painful sensations the patients will use the scale from 5-10 anchored at: = pain detection = slight pain = moderate pain = medium pain intensity = intense pain = unbearable pain
Time Frame
1.5 hours post dose
Secondary Outcome Measure Information:
Title
Time to Visual Analogue Scale 7 (VAS7) During Thermal Stimulation at 0.5 Hours Post Dose
Description
A probe (bag) was inserted 7cm above the lower esophageal sphincter (LES). Heat stimuli were applied by recirculation of heated water in the bag. Prior to recirculation the bag is filled with 7mL to ensure adequate mucosal contact. Water was heated up to a maximum of 63° C and the stimulation was continued until VAS 7 was reached. The intensities of the non-painful sensations were scored with the following descriptors added to facilitate the scoring: = vague perception of mild sensation = definite perception of mild sensation = vague perception of moderate sensation = definite perception of moderate sensation For painful sensations the patients will use the scale from 5-10 anchored at: = pain detection = slight pain = moderate pain = medium pain intensity = intense pain = unbearable pain
Time Frame
0.5 hours post dose
Title
Time to Visual Analogue Scale 7 (VAS7) During Thermal Stimulation at 2.5 Hours Post Dose
Description
A probe (bag) was inserted 7cm above the lower esophageal sphincter (LES). Heat stimuli were applied by recirculation of heated water in the bag. Prior to recirculation the bag is filled with 7mL to ensure adequate mucosal contact. Water was heated up to a maximum of 63° C and the stimulation was continued until VAS 7 was reached. The intensities of the non-painful sensations were scored with the following descriptors added to facilitate the scoring: = vague perception of mild sensation = definite perception of mild sensation = vague perception of moderate sensation = definite perception of moderate sensation For painful sensations the patients will use the scale from 5-10 anchored at: = pain detection = slight pain = moderate pain = medium pain intensity = intense pain = unbearable pain
Time Frame
2.5 hours post dose
Title
Volume at Visual Analogue Scale 7 (VAS7) During Mechanical Stimulation at 0.5 Hours Post Dose
Description
A probe (bag) was inserted 7cm above the lower esophageal sphincter (LES). Volume change in the bag was recorded continuously at each level of the visual analogue scale (VAS) and up to VAS7 (Volume at Visual Analogue Scale 7). The intensities of the non-painful sensations were scored with the following descriptors added to facilitate the scoring: = vague perception of mild sensation = definite perception of mild sensation = vague perception of moderate sensation = definite perception of moderate sensation For painful sensations the patients will use the scale from 5-10 anchored at: = pain detection = slight pain = moderate pain = medium pain intensity = intense pain = unbearable pain
Time Frame
0.5 hours post dose
Title
Volume at Visual Analogue Scale 7 (VAS7) During Mechanical Stimulation at 1.5 Hours Post-Dose
Description
A probe (bag) was inserted 7cm above the lower esophageal sphincter (LES). Volume change in the bag was recorded continuously at each level of the visual analogue scale (VAS) and up to VAS7 (Volume at Visual Analogue Scale 7). The intensities of the non-painful sensations were scored with the following descriptors added to facilitate the scoring: = vague perception of mild sensation = definite perception of mild sensation = vague perception of moderate sensation = definite perception of moderate sensation For painful sensations the patients will use the scale from 5-10 anchored at: = pain detection = slight pain = moderate pain = medium pain intensity = intense pain = unbearable pain
Time Frame
1.5 hours post dose
Title
Volume at Visual Analogue Scale 7 (VAS7) During Mechanical Stimulation at 2.5 Hours Post-Dose.
Description
A probe (bag) was inserted 7cm above the lower esophageal sphincter (LES). Volume change in the bag was recorded continuously at each level of the visual analogue scale (VAS) and up to VAS7 (Volume at Visual Analogue Scale 7). The intensities of the non-painful sensations were scored with the following descriptors added to facilitate the scoring: = vague perception of mild sensation = definite perception of mild sensation = vague perception of moderate sensation = definite perception of moderate sensation For painful sensations the patients will use the scale from 5-10 anchored at: = pain detection = slight pain = moderate pain = medium pain intensity = intense pain = unbearable pain
Time Frame
2.5 hours post dose
Title
Current at Visual Analogue Scale 7 (VAS7) During Electrical Stimulation 0.5 Hours Post Dose
Description
A probe (bag) was inserted 7cm above the lower esophageal sphincter (LES) and stimulations were performed at approximately 8 cm above the LES. The intensity of the stimuli is increased steadily in steps of 0.5 to 1 mA and the intensity corresponding to the VAS levels 1, 3, 5 and 7 were recorded. The current will be increased until the patient report moderate pain (VAS 7) or max 80 mA. The intensities of the non-painful sensations were scored with the following descriptors added to facilitate the scoring: = vague perception of mild sensation = definite perception of mild sensation = vague perception of moderate sensation = definite perception of moderate sensation For painful sensations the patients will use the scale from 5-10 anchored at: = pain detection = slight pain = moderate pain = medium pain intensity = intense pain = unbearable pain
Time Frame
0.5 hours post dose
Title
Current at Visual Analogue Scale 7 (VAS7) During Electrical Stimulation at 1.5 Hours Post Dose
Description
A probe (bag) was inserted 7cm above the lower esophageal sphincter (LES) and stimulations were performed at approximately 8 cm above the LES. The intensity of the stimuli is increased steadily in steps of 0.5 to 1 mA and the intensity corresponding to the VAS levels 1, 3, 5 and 7 were recorded. The current will be increased until the patient report moderate pain (VAS 7) or max 80 mA. The intensities of the non-painful sensations were scored with the following descriptors added to facilitate the scoring: = vague perception of mild sensation = definite perception of mild sensation = vague perception of moderate sensation = definite perception of moderate sensation For painful sensations the patients will use the scale from 5-10 anchored at: = pain detection = slight pain = moderate pain = medium pain intensity = intense pain = unbearable pain
Time Frame
1.5 hours post dose
Title
Current at Visual Analogue Scale 7 (VAS7) During Electrical Stimulation at 2.5 Hours Post Dose
Description
A probe (bag) was inserted 7cm above the lower esophageal sphincter (LES) and stimulations were performed at approximately 8 cm above the LES. The intensity of the stimuli is increased steadily in steps of 0.5 to 1 mA and the intensity corresponding to the VAS levels 1, 3, 5 and 7 were recorded. The current will be increased until the patient report moderate pain (VAS 7) or max 80 mA. The intensities of the non-painful sensations were scored with the following descriptors added to facilitate the scoring: = vague perception of mild sensation = definite perception of mild sensation = vague perception of moderate sensation = definite perception of moderate sensation For painful sensations the patients will use the scale from 5-10 anchored at: = pain detection = slight pain = moderate pain = medium pain intensity = intense pain = unbearable pain
Time Frame
2.5 hours post dose
Title
AUCt
Description
Area under the plasma concentration curve from time zero to the last quantifiable concentration
Time Frame
0 to 4 hours post dose
Title
Cmax
Description
Maximum plasma concentration
Time Frame
0 to 4 hours post dose
Title
Tmax
Description
Time of maximum plasma concentration
Time Frame
0 to 4 hours post dose
Title
SBP
Description
Supine Systolic Blood Pressure at 1.5 hours post dose
Time Frame
1.5 hours post dose
Title
DBP
Description
Supine Diastolic Blood Pressure at 1.5 hours post dose
Time Frame
1.5 hours post dose
Title
Pulse
Description
Supine Pulse at 1.5 hours post dose
Time Frame
1.5 hours post dose
Title
QTcF
Description
QT interval corrected for heart rate using Fredericia formula(QTcF) at 1.5 hours post dose
Time Frame
1.5 hours post dose
Title
Body Temperature
Description
Oral Body Temperature at 1.5 hours post dose
Time Frame
1.5 hours post dose
Title
Clinically Relevant Change of Laboratory Variables
Description
Number of participants with clinically relevant change of laboratory variables(clinical chemistry, haematology and urinalysis parameters)
Time Frame
Pre-entry to follow-up

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Provision of signed informed consent form BMI 18.5-35.0, inclusive Continuous PPI treatment for GERD during the last 4 weeks Exclusion Criteria: Patients that have not experienced any GERD symptoms improvement at all after PPI treatment Unstable or clinically significant disorders including cardiovascular, respiratory, renal, hepatic, metabolic, psychiatric, other gastrointestinal and esophageal disorders besides GERD Prior surgery of the upper GI tract
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marie Sundin
Organizational Affiliation
AstraZeneca R&D, Mölndal, Sweden
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Peter Funch-Jensen,, MD, PhD
Organizational Affiliation
Aarhus Hospital, Dept of Surgical Gastroenterology, Aarhus, Denmark
Official's Role
Principal Investigator
Facility Information:
Facility Name
Research Site
City
Århus C
Country
Denmark
Facility Name
Research Site
City
Goteborg
State/Province
Vastra Gotaland
Country
Sweden

12. IPD Sharing Statement

Citations:
PubMed Identifier
23320520
Citation
Krarup AL, Ny L, Gunnarsson J, Hvid-Jensen F, Zetterstrand S, Simren M, Funch-Jensen P, Hansen MB, Drewes AM. Randomized clinical trial: inhibition of the TRPV1 system in patients with nonerosive gastroesophageal reflux disease and a partial response to PPI treatment is not associated with analgesia to esophageal experimental pain. Scand J Gastroenterol. 2013 Mar;48(3):274-84. doi: 10.3109/00365521.2012.758769. Epub 2013 Jan 16.
Results Reference
derived

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Esophageal Hypersensitivity Study in Patients With Gastroesophageal Reflux Disease (GERD)

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