CEBE: Confocal Endomicroscopy for Barrett's Esophagus

• Sponsor: Johns Hopkins University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00487695
• Collaborator: American Society for Gastrointestinal Endoscopy (Other), Pentax, USA (Other)
• Enrollment: 46
• Location: 1
• Arms: 2
• Duration (Months): 17.1
• Patients Per Site Per Month: 2.7

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if confocal laser endomicroscopy (CLE) can improve detection of Barrett's esophagus, dysplasia, and early esophageal cancer.

Condition or Disease	Intervention/Treatment	Phase
Barrett's Esophagus; Esophageal Adenocarcinoma	Device: confocal laser endomicroscopy (CLE); Device: standard endoscopy (EGD)	Phase 3

Detailed Description

Barrett's esophagus is a leading cause of esophageal adenocarcinoma. Detection of dysplasia and early cancers in Barrett's esophagus can be challenging, time-consuming and expensive. Small lesions may be difficult to detect with standard endoscopy protocols. Confocal laser endomicroscopy (CLE) is a new type of endoscopy where a small confocal microscope is built into the tip of a standard endoscope. For this study, we are comparing confocal laser endomicroscopy (CLE) with targeted biopsies with standard endoscopy (EGD)and biopsy for Barrett's esophagus to determine if CLE is more effective for detecting dysplasia and cancer.

Participants with Barrett's esophagus in this study undergo 1) CLE with targeted mucosal biopsies (biopsy only taken if CLE shows abnormal tissue) and 2) standard EGD with biopsies. The order of procedures is randomized (some patients have CLE first while others have standard EGD first).

Study Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Confocal Laser Endomicroscopy for Improved Diagnosis of Barrett's Esophagus and Associated Neoplasia
• Study Start Date: Apr 1, 2007
• Actual Primary Completion Date: May 1, 2008
• Actual Study Completion Date: Sep 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: CLE followed by standard EGD Participants are randomized to have either confocal laser endomicroscopy (CLE) or standard endoscopy (EGD) first. Then 6 weeks later, they have the other procedure. This arm is for patients randomized to CLE followed by standard EGD	Device: confocal laser endomicroscopy (CLE); Confocal laser endomicroscopy is done by performing standard endoscopy, then using a microscope on the tip of the endoscope to obtain microscopic images of the mucosa. This is done by gently placing the tip of the endoscope on the lining of the esophagus.; Other Names: Pentax Confocal Laser Endomicroscope(EC3870KCILK) ; Device: standard endoscopy (EGD); Standard upper endoscopy (EGD) is performed using a regular upper endoscope, which is used to look at the lining of the esophagus.; Other Names: Olympus upper endoscope (GIF160)
Active Comparator: standard EGD followed by CLE Patients are randomized to either have standard endoscopy (EGD)or confocal laser endomicroscopy (CLE) first. The second procedure is then completed 6 weeks later. This arm is for patients who had standard endoscopy first.	Device: confocal laser endomicroscopy (CLE); Confocal laser endomicroscopy is done by performing standard endoscopy, then using a microscope on the tip of the endoscope to obtain microscopic images of the mucosa. This is done by gently placing the tip of the endoscope on the lining of the esophagus.; Other Names: Pentax Confocal Laser Endomicroscope(EC3870KCILK) ; Device: standard endoscopy (EGD); Standard upper endoscopy (EGD) is performed using a regular upper endoscope, which is used to look at the lining of the esophagus.; Other Names: Olympus upper endoscope (GIF160)

Outcome Measures

Primary Outcome Measures

1. Diagnostic Yield for Neoplasia in High Risk Patients(Suspected Neoplasia) [6 weeks]

   The yield for neoplasia is calculated by the number of biopsies showing neoplasia over the total number of biopsies taken (normal + neoplastic biopsies)

Secondary Outcome Measures

1. Mean Number of Biopsies With Neoplasia in High Risk Patients (Suspected Neoplasia) [6 weeks]

   The number of biopsies from each procedure (i.e. biopsies taken during CLE, or biopsies taken during standard EGD) that showed neoplasia. Neoplasia is high grade dysplasia or cancer. This analysis looks at patients with Barrett's suspected (but not known) neoplasia.

2. Mean Number of Biopsies Taken in High Risk Patients (Suspected Neoplasia) [6 weeks]

   The number of biopsies taken during each procedure (i.e. the number of biopsies taken during CLE, or the number of biopsies taken during standard EGD). Biopsies are taken during CLE only if CLE shows that the esophageal mucosa is abnormal. Esophageal biopsies are taken during standard EGD using a standard Barrett's esophagus protocol (4 quadrants, every 1-2 cm of the Barrett's esophagus). This analysis looks at the Barrett's patients with suspected (but not known) neoplasia.

3. Diagnostic Yield for Neoplasia in Barrett's Surveillance Patients [6 weeks]

   Our hypothesis was that the yield for neoplasia would be higher using confocal laser endomicroscopy compared to standard endoscopy. The null hypothesis would be that there is no difference in yield for neoplasia when CLE is used compared to standard endoscopy. This analysis looks specifically at patients who were referred for surveillance of Barrett's esophagus (no suspected neoplasia).

4. Mean Number of Biopsies With Neoplasia in Barrett's Surveillance Patients [6 weeks]

   The number of biopsies from each procedure (i.e. biopsies taken during CLE, or biopsies taken during standard EGD) that showed neoplasia. Neoplasia is high grade dysplasia or cancer. This analysis looks at patients undergoing surveillance EGD for Barrett's esophagus (no suspected neoplasia).

5. Mean Number of Biopsies Taken in Barrett's Surveillance Patients [6 weeks]

   The number of biopsies taken during each procedure (i.e. the number of biopsies taken during CLE, or the number of biopsies taken during standard EGD). Biopsies are taken during CLE only if CLE shows that the esophageal mucosa is abnormal. Esophageal biopsies are taken during standard EGD using a standard Barrett's esophagus protocol (4 quadrants, every 1-2 cm of the Barrett's esophagus). This analysis looks at the patients with Barrett's esophagus in the study who were undergoing surveillance EGD (no suspected neoplasia).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Barrett's esophagus or suspected Barrett's-associated neoplasia

• Age > 18

• Able to give informed consent

Exclusion Criteria:

• Known advanced malignant disease

• Allergy to the fluorescent contrast agent fluorescein sodium

• Coagulopathy or bleeding disorder

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Johns Hopkins Hospital	Baltimore	Maryland	United States	21205

Sponsors and Collaborators

• Johns Hopkins University
• American Society for Gastrointestinal Endoscopy
• Pentax, USA

Investigators

• Principal Investigator: Marcia I Canto, MD, MHS, Division of Gastroenterology, Johns Hopkins University School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT00487695
• Other Study ID Numbers: NA0002805
• First Posted: Jun 19, 2007
• Last Update Posted: Jun 22, 2021
• Last Verified: Jun 1, 2021

• Keywords provided by Johns Hopkins University: Barrett's esophagus; Esophageal adenocarcinoma; Endoscopy; Confocal laser endomicroscopy
• Additional relevant MeSH terms: Adenocarcinoma; Barrett Esophagus

Study Results

Participant Flow

Recruitment Details	Recruited from April 2007 to May 2008 from the gastroenterology clinics at Johns Hopkins University.
Pre-assignment Detail	None of the patients enrolled were excluded prior to group assignment. 1 patient dropped out prior to the first procedure.

Arm/Group Title	CLE Followed by Standard EGD	Standard EGD Followed by CLE
Arm/Group Description	Patients randomized to either CLE or standard endoscopy first. The other procedure was then performed 6 weeks later. This group was randomized to CLE first, followed by standard endoscopy	Patients in this group were randomized to have standard EGD followed by CLE 6 weeks later
Period Title: First Procedure
STARTED	23	23
COMPLETED	20	23
NOT COMPLETED	3	0
Period Title: First Procedure
STARTED	20	23
COMPLETED	19	20
NOT COMPLETED	1	3

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	Patients received both procedures (CLE and standard EGD), so baseline characteristics are reported for the group
Overall Participants	46
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	25 54.3%
>=65 years	21 45.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.8 (9.3)
Sex: Female, Male (Count of Participants)
Female	12 26.1%
Male	34 73.9%
Region of Enrollment (participants) [Number]
United States	46 100%

Outcome Measures

1. Primary Outcome

Title	Diagnostic Yield for Neoplasia in High Risk Patients(Suspected Neoplasia)
Description	The yield for neoplasia is calculated by the number of biopsies showing neoplasia over the total number of biopsies taken (normal + neoplastic biopsies)
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

Analysis was per protocol as the patients who did not undergo CLE could not be analyzed at all (cannot compare 2 procedures when only one (or zero) are performed. This analysis looks specifically at patients with Barrett's and suspected (but not known) neoplasia.

Arm/Group Title	Confocal Laser Endomicroscopy	Standard Endoscopy
Arm/Group Description	all patients had both confocal endomicroscopy and standard endoscopy in crossover fashion. For outcome, will compare the results of CLE and standard endoscopy.	all patients had both confocal endomicroscopy and standard endoscopy in crossover fashion. For outcome, will compare the results of CLE and standard endoscopy.
Measure Participants	16	16
Number [percent yield for neoplasia]	34 (0)	17 (0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Confocal Laser Endomicroscopy, Standard Endoscopy
	Comments	Our hypothesis was that the yield for neoplasia would be higher using confocal laser endomicroscopy compared to standard endoscopy. The null hypothesis would be that there is no difference in yield for neoplasia when CLE is used compared to standard endoscopy. We estimated that the yield for neoplasia would increase from 10% to 40% using CLE and the calculated sample size was 37. We planned to enroll 48 patients to allow for possible dropouts.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.01
	Comments
	Method	Wilcoxon signed rank
	Comments

2. Secondary Outcome

Title	Mean Number of Biopsies With Neoplasia in High Risk Patients (Suspected Neoplasia)
Description	The number of biopsies from each procedure (i.e. biopsies taken during CLE, or biopsies taken during standard EGD) that showed neoplasia. Neoplasia is high grade dysplasia or cancer. This analysis looks at patients with Barrett's suspected (but not known) neoplasia.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

Analysis was per protocol. Each participant was compared to self, so if the participant did not complete the study, no comparison could be made.

Arm/Group Title	Confocal Laser Endomicroscopy	Standard Endoscopy
Arm/Group Description	all patients had both confocal endomicroscopy and standard endoscopy in crossover fashion. For outcome, will compare the results of CLE and standard endoscopy.	all patients had both confocal endomicroscopy and standard endoscopy in crossover fashion. For outcome, will compare the results of CLE and standard endoscopy.
Measure Participants	16	16
Mean (Full Range) [mean number of biopsies with neoplasia]	3.1	3.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Confocal Laser Endomicroscopy, Standard Endoscopy
	Comments	The number of biopsies showing neoplasia was determined for each procedure (confocal laser endomicroscopy, standard EGD). These were compared.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.89
	Comments
	Method	Wilcoxon signed-rank
	Comments

3. Secondary Outcome

Title	Mean Number of Biopsies Taken in High Risk Patients (Suspected Neoplasia)
Description	The number of biopsies taken during each procedure (i.e. the number of biopsies taken during CLE, or the number of biopsies taken during standard EGD). Biopsies are taken during CLE only if CLE shows that the esophageal mucosa is abnormal. Esophageal biopsies are taken during standard EGD using a standard Barrett's esophagus protocol (4 quadrants, every 1-2 cm of the Barrett's esophagus). This analysis looks at the Barrett's patients with suspected (but not known) neoplasia.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

per protocol as participants would only have data to compare if they completed both endoscopies

Arm/Group Title	Confocal Laser Endomicroscopy	Standard Endoscopy
Arm/Group Description	all patients had both confocal endomicroscopy and standard endoscopy in crossover fashion. For outcome, will compare the results of CLE and standard endoscopy.	all patients had both confocal endomicroscopy and standard endoscopy in crossover fashion. For outcome, will compare the results of CLE and standard endoscopy.
Measure Participants	16	16
Mean (Full Range) [mean number of biopsies]	9.8	23.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Confocal Laser Endomicroscopy, Standard Endoscopy
	Comments	The null hypothesis would be that CLE does not decrease the number of biopsies needed to make a diagnosis compared to standard endoscopy
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	wilcoxon signed rank test
	Comments

4. Secondary Outcome

Title	Diagnostic Yield for Neoplasia in Barrett's Surveillance Patients
Description	Our hypothesis was that the yield for neoplasia would be higher using confocal laser endomicroscopy compared to standard endoscopy. The null hypothesis would be that there is no difference in yield for neoplasia when CLE is used compared to standard endoscopy. This analysis looks specifically at patients who were referred for surveillance of Barrett's esophagus (no suspected neoplasia).
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

Analysis was per protocol as the patients who did not undergo CLE could not be analyzed at all (cannot compare 2 procedures when only one (or zero) are performed).

Arm/Group Title	Confocal Laser Endomicroscopy	Standard Endoscopy
Arm/Group Description	all patients had both confocal endomicroscopy and standard endoscopy in crossover fashion. For outcome, will compare the results of CLE and standard endoscopy.	all patients had both confocal endomicroscopy and standard endoscopy in crossover fashion. For outcome, will compare the results of CLE and standard endoscopy.
Measure Participants	23	23
Number [percent yield for neoplasia]	0	0

5. Secondary Outcome

Title	Mean Number of Biopsies With Neoplasia in Barrett's Surveillance Patients
Description	The number of biopsies from each procedure (i.e. biopsies taken during CLE, or biopsies taken during standard EGD) that showed neoplasia. Neoplasia is high grade dysplasia or cancer. This analysis looks at patients undergoing surveillance EGD for Barrett's esophagus (no suspected neoplasia).
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

Analysis was per protocol. Each participant was compared to self, so if the participant did not complete the study, no comparison could be made.

Arm/Group Title	Confocal Laser Endomicroscopy	Standard Endoscopy
Arm/Group Description	all patients had both confocal endomicroscopy and standard endoscopy in crossover fashion. For outcome, will compare the results of CLE and standard endoscopy.	all patients had both confocal endomicroscopy and standard endoscopy in crossover fashion. For outcome, will compare the results of CLE and standard endoscopy.
Measure Participants	23	23
Mean (Full Range) [number of biopsies with neoplasia]	0	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Confocal Laser Endomicroscopy, Standard Endoscopy
	Comments	The number of biopsies showing neoplasia was determined for each procedure (confocal laser endomicroscopy, standard EGD). These were compared. This analysis looks at the patients referred for Barrett's surveillance EGD (no suspected neoplasia).
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	1.0
	Comments
	Method	Wilcoxon signed-rank
	Comments

6. Secondary Outcome

Title	Mean Number of Biopsies Taken in Barrett's Surveillance Patients
Description	The number of biopsies taken during each procedure (i.e. the number of biopsies taken during CLE, or the number of biopsies taken during standard EGD). Biopsies are taken during CLE only if CLE shows that the esophageal mucosa is abnormal. Esophageal biopsies are taken during standard EGD using a standard Barrett's esophagus protocol (4 quadrants, every 1-2 cm of the Barrett's esophagus). This analysis looks at the patients with Barrett's esophagus in the study who were undergoing surveillance EGD (no suspected neoplasia).
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

Analysis was per protocol. Each participant was compared to self, so if the participant did not complete, the study, no comparison could be made. The patients in this analysis were referred for surveillance of Barrett's esophagus (no suspected neoplasia).

Arm/Group Title	Confocal Laser Endomicroscopy	Standard Endoscopy
Arm/Group Description	all patients had both confocal endomicroscopy and standard endoscopy in crossover fashion. For outcome, will compare the results of CLE and standard endoscopy.	all patients had both confocal endomicroscopy and standard endoscopy in crossover fashion. For outcome, will compare the results of CLE and standard endoscopy.
Measure Participants	23	23
Mean (Full Range) [mean number of biopsies]	1.7	12.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Confocal Laser Endomicroscopy, Standard Endoscopy
	Comments	The null hypothesis would be that CLE does not decrease the number of biopsies needed to make a diagnosis compared to standard endoscopy
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon signed-rank
	Comments

Adverse Events

Time Frame	Adverse event data was collected after each procedure and for an average of one month after the last procedure.
Arm/Group Title	Confocal Laser Endomicroscopy		Standard EGD
Arm/Group Description	Adverse even reporting is being done by procedure type (ie confocal laser endomicroscopy vs. standard endoscopy)		Adverse even reporting is being done by procedure type (ie confocal laser endomicroscopy vs. standard endoscopy)
All Cause Mortality
	Confocal Laser Endomicroscopy		Standard EGD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Confocal Laser Endomicroscopy		Standard EGD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/39 (2.6%)		0/39 (0%)
Infections and infestations
post-procedure pneumonia	1/39 (2.6%)	1	0/39 (0%)	0
Other (Not Including Serious) Adverse Events
	Confocal Laser Endomicroscopy		Standard EGD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/39 (0%)		0/39 (0%)

Limitations/Caveats

Relatively small study (39 patients) and performed at a tertiary care, referral center, which can reduce generalizability.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.