Diagnostic Methods for Achalasia

Recruiting at 1 trial location

Overseen By Anand Jain, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Emory University

Disqualifiers: Pregnancy, Prisoners, Cardiac disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

80 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is the muscle layer biopsy during per-oral endoscopic myotomy (POEM) safe for humans?

The research indicates that muscle layer biopsy during per-oral endoscopic myotomy (POEM) is evaluated for safety and efficacy, suggesting it is generally considered safe for humans. ^{1 2 3 4 5}

How is the esophageal muscle biopsy treatment for achalasia different from other treatments?

The esophageal muscle biopsy treatment for achalasia is unique because it involves directly sampling the muscle layer of the esophagus, which is not typically done in routine procedures. This approach can help identify specific cellular changes, like eosinophilic infiltration, that are not detectable with standard surface biopsies, potentially offering more precise diagnostic information. ^{1 6 7 8 9}

What is the purpose of this trial?

This trial uses a new technology to map the lower esophageal sphincter in patients with achalasia. It helps doctors understand if the problem is due to muscle stiffness or nerve issues, allowing for earlier and better treatment. EsoFLIP is a new technology used for esophageal dilation in achalasia.

Research Team

Anand Jain, MD

Principal Investigator

Emory University

Eligibility Criteria

Adults over 18 with achalasia or esophageal motility disorders, who are undergoing specific treatments like Heller myotomy or per oral endoscopic myotomy. They must have been evaluated at Emory facilities and not be pregnant, imprisoned, cognitively impaired without consent ability, have severe cardiac issues, respiratory diseases, urinary retention problems, glaucoma, myasthenia gravis or poor kidney function.

Inclusion Criteria

Male or female patients, age 18 and above

You have recently had surgery or a procedure to treat your esophageal motility disorder.

Has a diagnosis of achalasia or an esophageal motility disorder with confirmed evaluation by one of the following modalities: functional lumen imaging probe (FLIP) or high resolution esophageal manometry (for Aim 1)

Exclusion Criteria

Pregnant women

Prisoners

Cognitively impaired adults unable to provide informed consent

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pharmacologic Challenge

Measurement of esophageal response to atropine using functional lumen imaging probe (FLIP)

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Atropine challenge
• Esophageal muscle biopsy

Trial Overview The trial is testing how muscle fibrosis relates to lower esophageal sphincter measurements using a new technology called FLIP Topography after an atropine challenge. It aims to improve early intervention in achalasia by understanding the condition better through these tests and biopsies.

Participant Groups

Group I: Pharmacologic challenge Experimental Treatment 2 Interventions

Measurement of esophageal response to atropine using functional lumen imaging probe (FLIP)

Esophageal muscle biopsy is already approved in United States, European Union for the following indications:

Approved in United States as Esophageal muscle biopsy for:

• Diagnosis of achalasia
• Evaluation of esophageal motility disorders

Approved in European Union as Esophageal muscle biopsy for:

• Diagnosis of achalasia
• Evaluation of esophageal motility disorders
• Investigation of eosinophilic esophagitis

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Findings from Research

In a study of 20 patients with achalasia undergoing per-oral endoscopic myotomy (POEM), muscle layer biopsies were safely performed without complications, demonstrating the feasibility of this approach for further research.

The study found eosinophilic infiltration in only 15% of patients in the distal esophageal mucosa, with no evidence of eosinophilic esophagitis or infiltration in the muscle layer, suggesting that achalasia may be linked to immune or autoimmune reactions rather than eosinophilic infiltration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous Examination of Eosinophil Infiltration in Esophageal Mucosa and Muscle in Patients with Achalasia: Direct Biopsy of the Esophageal Muscle at Per-oral Endoscopic Myotomy. Chen, H., Calderon, LF., Shah, R., et al.[2022]

In a study of 114 achalasia patients undergoing peroral endoscopic myotomy (POEM), those with thinner cardiac muscularis propria (MP) had significantly poorer clinical outcomes compared to those with thicker MP, indicating that MP thickness may predict treatment failure.

While the rate of perioperative adverse events (AEs) was slightly higher in patients with thinner MP, it was not statistically significant, suggesting that MP thickness primarily affects long-term treatment success rather than immediate surgical safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The relationship between cardiac muscularis propria and clinical outcomes of peroral endoscopic myotomy in achalasia. He, QL., Chen, XB., Lu, DH., et al.[2022]

Suction biopsies of the esophagus provided more comprehensive tissue samples and better orientation compared to endoscopic biopsies, with 92.5% of suction biopsies yielding deep tissue layers, while endoscopic biopsies only provided squamous epithelium.

The study found a low false-positive rate for gastroesophageal reflux in asymptomatic volunteers, highlighting the reliability of esophageal biopsies in evaluating reflux conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reassessment of esophageal histology in normal subjects: a comparison of suction and endoscopic techniques. Fink, SM., Barwick, KW., Winchenbach, CL., et al.[2019]

Cineradiology is essential for accurately assessing achalasia, allowing for tailored surgical approaches based on the specific involvement of the esophagus and lower esophageal sphincter (LES).

From 1984 to 2002, treatment of 148 achalasia patients showed that customizing the length of myotomy based on individual physiopathological characteristics significantly improved post-operative outcomes, particularly in controlling dysphagia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Surgical treatment of esophageal achalasia. Personal trend]. Maiorana, AM., Sanzo, AC., Ciulla, A., et al.[2006]

In a study of 122 patients with achalasia, those with type I achalasia had significantly fewer interstitial cells of Cajal (ICCs) compared to those with type II achalasia, indicating a potential link between ICC count and disease severity.

Patients with recurrent achalasia had lower ICC counts than those without recurrence, suggesting that ICC levels may be associated with clinical prognosis and outcomes after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Number of Interstitial Cells of Cajal Differs Among Different Subtypes of Achalasia and is Related to Patients' Prognosis. Chen, S., Zhang, M., Liang, M., et al.[2023]

In a study of 32 patients with achalasia, significant histological changes such as esophagitis and muscularis mucosae atrophy were found, indicating that even early achalasia shows notable tissue damage compared to controls.

The study suggests that early detection and management of achalasia are crucial, as early histological changes like the pinstripe pattern and epithelial wave can lead to more severe conditions if not addressed promptly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Full-layer mucosal histology in achalasia: Histological epithelial wave is characteristic in "pinstripe pattern"-positive achalasia. Sato, H., Takahashi, K., Nakajima, N., et al.[2018]

In a study of 109 patients undergoing muscle biopsy, 11% had no prior indications of myopathy, yet pathology was found in about two-thirds of these cases, highlighting the diagnostic value of muscle biopsy even when initial tests are normal.

Inflammation was the most common finding, present in 42% of cases, suggesting that muscle biopsy can effectively detect underlying inflammatory conditions despite normal muscle strength and creatine-kinase levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[THE VALUE OF MUSCLE BIOPSY IN PATIENTS WITHOUT WEAKNESS, HIGH CREATINE KINASE OR MYOPATHY ON ELECTROMYOGRAPHY]. Dori, A., Shelestovich, N., Gayster, A., et al.[2019]

Patients with achalasia exhibit distinct clinical and histopathological features compared to those with refractory GERD, including higher Eckardt scores, more esophageal food retention, and specific histological changes like hypertrophy of the muscularis mucosae and petechiae formation.

A predictive model using the Eckardt score, endoscopic findings, and histopathological criteria can help differentiate achalasia from GERD, potentially leading to earlier diagnosis and treatment for patients with this rare esophageal disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of Symptom Profile, Endoscopic Findings, and Esophageal Mucosal Histopathology Helps to Differentiate Achalasia from Refractory Gastroesophageal Reflux Disease. Yeh, CC., Shun, CT., Tseng, LW., et al.[2021]

Recent advancements in histological techniques, such as immunohistochemistry and electron microscopy, have significantly improved the diagnosis of various muscle disorders, including myopathies and muscle dystrophies.

For accurate diagnosis, it is crucial to obtain a properly sized muscle biopsy (3x1x1 cm) from a moderately affected area, and to ensure immediate and appropriate transport to a specialized laboratory for analysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Muscle biopsy : Indications and techniques]. Bergmann, M., Weis, J., Probst-Cousin, S.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Simultaneous Examination of Eosinophil Infiltration in Esophageal Mucosa and Muscle in Patients with Achalasia: Direct Biopsy of the Esophageal Muscle at Per-oral Endoscopic Myotomy. [2022]

2. France pubmed.ncbi.nlm.nih.gov

The relationship between cardiac muscularis propria and clinical outcomes of peroral endoscopic myotomy in achalasia. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Reassessment of esophageal histology in normal subjects: a comparison of suction and endoscopic techniques. [2019]

4. Italy pubmed.ncbi.nlm.nih.gov

[Surgical treatment of esophageal achalasia. Personal trend]. [2006]

5. United States pubmed.ncbi.nlm.nih.gov

The Number of Interstitial Cells of Cajal Differs Among Different Subtypes of Achalasia and is Related to Patients' Prognosis. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Full-layer mucosal histology in achalasia: Histological epithelial wave is characteristic in "pinstripe pattern"-positive achalasia. [2018]

7. Israel pubmed.ncbi.nlm.nih.gov

[THE VALUE OF MUSCLE BIOPSY IN PATIENTS WITHOUT WEAKNESS, HIGH CREATINE KINASE OR MYOPATHY ON ELECTROMYOGRAPHY]. [2019]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Combination of Symptom Profile, Endoscopic Findings, and Esophageal Mucosal Histopathology Helps to Differentiate Achalasia from Refractory Gastroesophageal Reflux Disease. [2021]

9. Germany pubmed.ncbi.nlm.nih.gov

[Muscle biopsy : Indications and techniques]. [2021]