HistopathologyNCT04463095
Esophageal Mucosal Changes in Achalasia Cardia and Reversibility After Per Oral Endoscopic Myotomy - A Pilot Study
An observational study of Histopathology, run by Asian Institute of Gastroenterology, India at 1 site in India.
Trial summary
Esophageal mucosal changes in long standing achalasia cardia and reversibility after per oral endoscopic myotomy - A pilot study Aims and Objectives: To study mucosal changes in patients with achalasia cardia To study potential malignant histopathological findings in long standing achalasia cardia To assess… Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Histopathology
- What is being tested?
- PER ORAL ENDOSCOPY MYOTOMY (POEM)
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- How many people
- 30 participants
- Where
- 1 siteIndia
- Study dates
- 30 Jun 2020to 1 Sep 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Since the present study is pilot based in assessing the primary outcome, it has been decided to cover 30 patients and follow up at 3 months. Hence no power calculation is used to estimate the sample size.
Who may be able to join
- • All patients of achalasia cardia who will undergo POEM and an esophageal mucosal biopsy at 3 months of follow up
Who cannot join
- • Patients of achalasia cardia not undergoing POEM or an esophageal mucosal biopsy at 3 months of follow up
- Upper gastro-intestinal surgically altered anatomy ( apart from previous Heller Myotomy )
- Pregnancy
- Patients not giving consent for participation
Trial locations and contacts
1 site in 1 country.
India1 site
Asian institute of Gastroenterology/AIG Hospitals
Hyderabad, Telangana, 500082
About this study
Official title: Esophageal Mucosal Changes in Long Standing Achalasia Cardia and Reversibility After Per Oral Endoscopic Myotomy ( POEM )
Esophageal mucosal changes in long standing achalasia cardia and reversibility after per oral endoscopic myotomy - A pilot study
Aims and Objectives:
Read more
- To study mucosal changes in patients with achalasia cardia
- To study potential malignant histopathological findings in long standing achalasia cardia
- To assess reversibility of mucosal changes after POEM
- To study co-relation of mucosal histopathology with predictors of sub-mucosal fibrosis
- To study muscle biopsy by light microscopy and electron microscopy for viral inclusions
Materials and Methods:
- Study Area - Patients of achalasia cardia undergoing POEM in Asian Institute of Gastroenterology.
- Study Design - Cross sectional study
Inclusion Criteria:
•All patients of achalasia cardia who will undergo POEM and an esophageal mucosal biopsy at 3 months of follow up
Exclusion Criteria:
- Patients of achalasia cardia not undergoing POEM or an esophageal mucosal biopsy at 3 months of follow up
- Upper gastro-intestinal surgically altered anatomy ( apart from previous Heller Myotomy )
- Pregnancy
- Patients not giving consent for participation
- End Point( Length of follow up )- 3 months after POEM - single follow up.
Study Procedure:
Before POEM, all patients will undergo symptom evaluation, esophagogastroduodenoscopy (EGD), high resolution esophageal manometry and timed barium esophagogram.The diagnosis of achalasia will be based on a combination of clinical presentation, esophagogastroduodenoscopy, barium esophagogram and high resolution manometric findings.
Symptoms will be classified by using the Eckardt score.Type of Achalasia will be classified according to the Chicago classification. Esophagus shape (sigmoid vs nonsigmoid), presence of hiatus hernia, presence of esophagitis will be assessed on esophagogastroduodenoscopy. Duration since first symptoms of achalasia will be recorded.
All patients fulfilling the inclusion criteria will undergo Per Oral Endoscopic Myotomy (POEM). During POEM, a mucosal biopsy and a muscle biopsy of the Esophagus will be taken. Patients will be followed up at a single time, 3 months after POEM. During the follow up visit, patients will undergo esophagogastroduodenoscopy guided mucosal biopsy of the Esophagus. Patients will be divided into two groups based on the duration of symptoms of achalasia- Those having symptoms for 1 year or less and those having symptoms for more than 5 years. Histopathological changes in the Esophagus and reversibility of these changes after POEM will be compared between the two study groups to draw a conclusion.
Read the detailed description
Introduction and Background:
Achalasia cardiais a rare, chronic, esophageal motility disorder with an estimated annual prevalence of 1 per 1,00,000 subjects. The disease can occur at all ages, but the incidence seems to increase with age. The predominant symptoms are dysphagia and regurgitation, because of the impaired relaxation of the lower esophageal sphincter (LES) and the loss of normal peristalsis.Achalasia is a neurodegenerative disease resulting from an inflammatory and/or autoimmune process ultimately leading to aganglionosis. The etiology and pathogenesis of achalasia is still unknown. The primary pathophysiologic abnormality is a loss of the intrinsic inhibitory innervation of the lower esophageal sphincter (LES) and the segment of smooth musculature of the esophageal body. The resultant denervation and reduction of post-ganglionic nerve fibers have been postulated to be related to the hypertensive or non-relaxing LES in patients with achalasia.Esophagectomy or surgical myotomy specimens have demonstratedabsence or reduction in ganglion cells as well as varying degrees of cytotoxic T-cell inflammation in the myenteric plexus of patients with achalasia. Studies demonstrating an association between achalasia and certain HLA phenotypes, and an increased immunologic response to Herpes Simplex Virus-1 (HSV-1) in the serum and LES myenteric plexusof achalasia patients further support the notion of inflammation playing a central role in pathogenesis.However, it is not known whether this inflammation is part of the process that leads to the loss of the plexus, or whether it is secondary to the outflow obstruction with consecutive stasis in achalasia. Persistent esophageal distension with retention of foods and fluids, bacterial overgrowth, and impaired clearance of regurgitated acid and gastric contents lead to chronic inflammation and passively cause dysplasia and carcinoma. The prognosis of patients who develop such carcinomas remains poor. The aim of therapy is to reduce food stasis, which might interrupt the progression to carcinoma and thus reduce the risk of squamous cell carcinoma.
No currently available treatment options result in regeneration of myenteric neurons to bring back esophageal motility. However, lowering LES pressure can significantly reduce symptoms and improve quality of life. To achieve this outcome (LES pressure reduction), therapeutic techniques have been modified from time to time. Graded pneumatic balloon dilatation (PBD) has replaced conventional one-time dilatation and open Heller's myotomy has cleared the way for laparoscopic Heller's myotomy (LHM) with fundoplication.Recently, per oral endoscopic myotomy (POEM) was introduced by Inoue et al. as a less invasive and effective curative treatment option with minimal complications.Peroral endoscopic myotomy (POEM)combines thelong-term efficacy of a myotomy with the benefits of an endoscopic, minimally invasive procedure.Other therapeutic options include endoscopic balloon dilatation and surgical myotomy. Endoscopic balloon dilatation is still widely performed because of its relative non-invasiveness and simplicity, but it has a relatively lower success rate and often requires multiple treatment sessions. Surgical myotomy has been thought to be the curative therapeutic choice for symptomatic achalasia. However, it requires skin incisions and additional anti-reflux surgical intervention.Unlike surgical myotomy, POEM preserves the anatomical integrity of the LES and possibly minimizes postoperative reflux.
Rationale of the study:
- There have been very few studies systematically analysing the histopathological changes in the mucosa and muscle of the Esophagus in Achalasia Cardia.
- Therefore we want to study the histopathological changes in the mucosa and muscle of the Esophagus in achalasia cardia patients and observe how the histopathological changes differ between early achalasia cardia and long-standing achalasia cardia.
- Achalasia Cardia is a potential pre-malignant condition which can lead to esophageal carcinoma.
- Principal investogator want to study the pre-malignant and malignant changes in the Esophagus in achalasia cardia patients.
- Also want to study whether per oral endoscopic myotomy ( POEM ) reverses the histopathological and pre-malignant changes in the Esophagus.
- Conditions
- Histopathology
- Being tested
- PER ORAL ENDOSCOPY MYOTOMY (POEM)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PER ORAL ENDOSCOPY MYOTOMY (POEM)Procedure or surgery
Peroral endoscopic myotomy (POEM)combines thelong-term efficacy of a myotomy with the benefits of an endoscopic, minimally invasive procedure.Other therapeutic options include endoscopic balloon dilatation and surgical myotomy. Endoscopic balloon dilatation is still widely performed because of its relative non-invasiveness and simplicity, but it has a relatively lower success rate and often requires multiple treatment sessions. Surgical myotomy has been thought to be the curative therapeutic choice for symptomatic achalasia. However, it requires skin incisions and additional anti-reflux surgical intervention.Unlike surgical myotomy, POEM preserves the anatomical integrity of the LES and possibly minimizes postoperative reflux.
What is being measured
The primary outcome is the main question the study is designed to answer.
1.To study mucosal changes in patients with achalasia cardia
Number of ganglion cells will be measured in the mucosal biopsy (normal number of ganglion cells are 2 to 12 per mm on Histopathological examination). The size of the ganglion cells will be measured.(normal size of ganglion cells is 10 to 40 microns). Median number of neurons will be measured.(normal median number of neurons are 2 to 6 on histopathological examination).
Measured: 12 weeks
2. To study potential malignant histopathological findings in long standing achalasia cardia
The mean Ki-67 and mean p53 positive ratio will be measured in the histopathological examination.
Measured: 12 weeks
Secondary outcomes (2)
3.To study co-relation of mucosal histopathology with predictors of sub-mucosal fibrosis
The fibrosis score will be measured in the histopathological examination.
Measured: 12 weeks
4. To evaluate reversibility of mucosal changes after per oral endoscopic myotomy (POEM )
Number of ganglion cells will be measured in the mucosal biopsy (normal number of ganglion cells are 2 to 12 per mm on Histopathological examination). The size of the ganglion cells will be measured.(normal size of ganglion cells is 10 to 40 microns). Median number of neurons will be measured.(normal median number of neurons are 2 to 6 on histopathological examination). These findings will be measured 12 weeks post POEM.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2020
- Study start30 Jun 2020
- Primary completion1 Jan 2021
- Study completion1 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HistopathologyStudies of the same condition, open and under way.
- More trials run by Asian Institute of Gastroenterology, IndiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Asian Institute of Gastroenterology, India
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mohan Ramchandani, Asian Institute of Gastroenterology, India
- Investigators
- Dr Pranav Milind Ambardekar, MBBS MD, Principal investigator, Asian institute of Gastroenterology/AIG Hospitals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04463095
- Sponsor's protocol ID
- POEM EM
- Status last verified
- Jul 2020
- First submitted
- 12 Jun 2020
- Last updated
- 16 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Esophageal Mucosal Changes in Long Standing Achalasia Cardia and Reversibility After Per Oral Endoscopic Myotomy ( POEM )
- ClinicalTrials.gov ID
- NCT04463095
- Acronym / sponsor ID
- POEM EM
- Conditions
- Histopathology
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Asian Institute of Gastroenterology, IndiaUniversity, hospital or other
- Study start
- 30 Jun 2020 (actual)
- Primary completion
- 1 Jan 2021 (actual)
- Study completion
- 1 Sep 2021 (actual)
- First posted
- 9 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Esophageal mucosal changes in long standing achalasia cardia and reversibility after per oral endoscopic myotomy - A pilot study
Aims and Objectives:
- To study mucosal changes in patients with achalasia cardia
- To study potential malignant histopathological findings in long standing achalasia cardia
- To assess reversibility of mucosal changes after POEM
- To study co-relation of mucosal histopathology with predictors of sub-mucosal fibrosis
- To study muscle biopsy by light microscopy and electron microscopy for viral inclusions
Materials and Methods:
- Study Area - Patients of achalasia cardia undergoing POEM in Asian Institute of Gastroenterology.
- Study Design - Cross sectional study
Inclusion Criteria:
•All patients of achalasia cardia who will undergo POEM and an esophageal mucosal biopsy at 3 months of follow up
Exclusion Criteria:
- Patients of achalasia cardia not undergoing POEM or an esophageal mucosal biopsy at 3 months of follow up
- Upper gastro-intestinal surgically altered anatomy ( apart from previous Heller Myotomy )
- Pregnancy
- Patients not giving consent for participation
- End Point( Length of follow up )- 3 months after POEM - single follow up.
Study Procedure:
Before POEM, all patients will undergo symptom evaluation, esophagogastroduodenoscopy (EGD), high resolution esophageal manometry and timed barium esophagogram.The diagnosis of achalasia will be based on a combination of clinical presentation, esophagogastroduodenoscopy, barium esophagogram and high resolution manometric findings.
Symptoms will be classified by using the Eckardt score.Type of Achalasia will be classified according to the Chicago classification. Esophagus shape (sigmoid vs nonsigmoid), presence of hiatus hernia, presence of esophagitis will be assessed on esophagogastroduodenoscopy. Duration since first symptoms of achalasia will be recorded.
All patients fulfilling the inclusion criteria will undergo Per Oral Endoscopic Myotomy (POEM). During POEM, a mucosal biopsy and a muscle biopsy of the Esophagus will be taken. Patients will be followed up at a single time, 3 months after POEM. During the follow up visit, patients will undergo esophagogastroduodenoscopy guided mucosal biopsy of the Esophagus. Patients will be divided into two groups based on the duration of symptoms of achalasia- Those having symptoms for 1 year or less and those having symptoms for more than 5 years. Histopathological changes in the Esophagus and reversibility of these changes after POEM will be compared between the two study groups to draw a conclusion.
Detailed description
Introduction and Background:
Achalasia cardiais a rare, chronic, esophageal motility disorder with an estimated annual prevalence of 1 per 1,00,000 subjects. The disease can occur at all ages, but the incidence seems to increase with age. The predominant symptoms are dysphagia and regurgitation, because of the impaired relaxation of the lower esophageal sphincter (LES) and the loss of normal peristalsis.Achalasia is a neurodegenerative disease resulting from an inflammatory and/or autoimmune process ultimately leading to aganglionosis. The etiology and pathogenesis of achalasia is still unknown. The primary pathophysiologic abnormality is a loss of the intrinsic inhibitory innervation of the lower esophageal sphincter (LES) and the segment of smooth musculature of the esophageal body. The resultant denervation and reduction of post-ganglionic nerve fibers have been postulated to be related to the hypertensive or non-relaxing LES in patients with achalasia.Esophagectomy or surgical myotomy specimens have demonstratedabsence or reduction in ganglion cells as well as varying degrees of cytotoxic T-cell inflammation in the myenteric plexus of patients with achalasia. Studies demonstrating an association between achalasia and certain HLA phenotypes, and an increased immunologic response to Herpes Simplex Virus-1 (HSV-1) in the serum and LES myenteric plexusof achalasia patients further support the notion of inflammation playing a central role in pathogenesis.However, it is not known whether this inflammation is part of the process that leads to the loss of the plexus, or whether it is secondary to the outflow obstruction with consecutive stasis in achalasia. Persistent esophageal distension with retention of foods and fluids, bacterial overgrowth, and impaired clearance of regurgitated acid and gastric contents lead to chronic inflammation and passively cause dysplasia and carcinoma. The prognosis of patients who develop such carcinomas remains poor. The aim of therapy is to reduce food stasis, which might interrupt the progression to carcinoma and thus reduce the risk of squamous cell carcinoma.
No currently available treatment options result in regeneration of myenteric neurons to bring back esophageal motility. However, lowering LES pressure can significantly reduce symptoms and improve quality of life. To achieve this outcome (LES pressure reduction), therapeutic techniques have been modified from time to time. Graded pneumatic balloon dilatation (PBD) has replaced conventional one-time dilatation and open Heller's myotomy has cleared the way for laparoscopic Heller's myotomy (LHM) with fundoplication.Recently, per oral endoscopic myotomy (POEM) was introduced by Inoue et al. as a less invasive and effective curative treatment option with minimal complications.Peroral endoscopic myotomy (POEM)combines thelong-term efficacy of a myotomy with the benefits of an endoscopic, minimally invasive procedure.Other therapeutic options include endoscopic balloon dilatation and surgical myotomy. Endoscopic balloon dilatation is still widely performed because of its relative non-invasiveness and simplicity, but it has a relatively lower success rate and often requires multiple treatment sessions. Surgical myotomy has been thought to be the curative therapeutic choice for symptomatic achalasia. However, it requires skin incisions and additional anti-reflux surgical intervention.Unlike surgical myotomy, POEM preserves the anatomical integrity of the LES and possibly minimizes postoperative reflux.
Rationale of the study:
- There have been very few studies systematically analysing the histopathological changes in the mucosa and muscle of the Esophagus in Achalasia Cardia.
- Therefore we want to study the histopathological changes in the mucosa and muscle of the Esophagus in achalasia cardia patients and observe how the histopathological changes differ between early achalasia cardia and long-standing achalasia cardia.
- Achalasia Cardia is a potential pre-malignant condition which can lead to esophageal carcinoma.
- Principal investogator want to study the pre-malignant and malignant changes in the Esophagus in achalasia cardia patients.
- Also want to study whether per oral endoscopic myotomy ( POEM ) reverses the histopathological and pre-malignant changes in the Esophagus.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Since the present study is pilot based in assessing the primary outcome, it has been decided to cover 30 patients and follow up at 3 months. Hence no power calculation is used to estimate the sample size.
Key inclusion criteria (1 listed)
- • All patients of achalasia cardia who will undergo POEM and an esophageal mucosal biopsy at 3 months of follow up
Key exclusion criteria (4 listed)
- • Patients of achalasia cardia not undergoing POEM or an esophageal mucosal biopsy at 3 months of follow up
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PER ORAL ENDOSCOPY MYOTOMY (POEM)Peroral endoscopic myotomy (POEM)combines thelong-term efficacy of a myotomy with the benefits of an endoscopic, minimally invasive procedure.Other therapeutic options include endoscopic balloon dilatation and surgical myotomy. Endoscopic balloon dilatation is still widely performed because of its relative non-invasiveness and simplicity, but it has a relatively lower success rate and often requires multiple treatment sessions. Surgical myotomy has been thought to be the curative therapeutic choice for symptomatic achalasia. However, it requires skin incisions and additional anti-reflux surgical intervention.Unlike surgical myotomy, POEM preserves the anatomical integrity of the LES and possibly minimizes postoperative reflux. | Procedure or surgery | – |
Primary outcome
1.To study mucosal changes in patients with achalasia cardia
Time frame: 12 weeks
Number of ganglion cells will be measured in the mucosal biopsy (normal number of ganglion cells are 2 to 12 per mm on Histopathological examination). The size of the ganglion cells will be measured.(normal size of ganglion cells is 10 to 40 microns). Median number of neurons will be measured.(normal median number of neurons are 2 to 6 on histopathological examination).
2. To study potential malignant histopathological findings in long standing achalasia cardia
Time frame: 12 weeks
The mean Ki-67 and mean p53 positive ratio will be measured in the histopathological examination.
2 secondary outcomes
3.To study co-relation of mucosal histopathology with predictors of sub-mucosal fibrosis
Time frame: 12 weeks
4. To evaluate reversibility of mucosal changes after per oral endoscopic myotomy (POEM )
Time frame: 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Apr 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dr Pranav Milind Ambardekar, MBBS MD principal investigator
Asian institute of Gastroenterology/AIG Hospitals
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Histopathology, run by Asian Institute of Gastroenterology, India at 1 site in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
1.To study mucosal changes in patients with achalasia cardia (time frame: 12 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Apr 2024.