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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to better understand achalasia, a condition affecting how the esophagus moves food toward the stomach. Researchers will use a new tool to measure the esophagus muscle's reaction after administering a specific medication (Atropine challenge). The trial involves taking a small piece of muscle from the esophagus for detailed study. Individuals diagnosed with achalasia or a similar esophageal motility disorder and receiving treatment at Emory University may be suitable candidates for this trial. As a Phase 4 trial, the research focuses on understanding how an already FDA-approved and effective treatment can benefit more patients.

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.

What is the safety track record for the Atropine challenge and Esophageal muscle biopsy?

Research shows that atropine, used in this study to test the esophagus, can be safe when used carefully. Previous studies found that atropine lowers pressure in the esophagus muscles, aiding muscle contraction problems. Most people tolerate it well, especially under medical supervision.

However, atropine can have side effects. These may include changes in behavior or mental state, and in rare cases, more serious effects like seizures or breathing issues. Such effects are uncommon, particularly when the drug is used in a clinical setting with careful monitoring.

Participants can feel reassured that this treatment has been studied before and is generally considered safe when used correctly. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the diagnostic method involving esophageal muscle biopsy for achalasia because it offers a more direct way to understand muscle function in the esophagus. Unlike current treatments like pneumatic dilation or Heller myotomy, which focus on alleviating symptoms, this method seeks to uncover the underlying muscle response. By using atropine to measure esophageal reaction through a functional lumen imaging probe (FLIP), this approach could lead to more tailored and effective treatments by providing deeper insights into the condition's physiology.

What evidence suggests that these diagnostic methods are effective for achalasia?

Research has shown that atropine can affect the esophageal muscles in people with achalasia. One study demonstrated that atropine altered muscle response in patients with a specific type of achalasia, enhancing understanding of esophageal function in these cases. Another study found that atropine impacts the lower esophageal sphincter (LES), which could aid in diagnosing muscle issues related to achalasia. In this trial, participants will undergo a pharmacologic challenge to measure the esophageal response to atropine using new imaging technology. Atropine's role in altering muscle response is crucial for advancing knowledge about achalasia and potentially improving diagnosis and treatment. ^{1 2 4 6 7}

Who Is on the Research Team?

Anand Jain, MD

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12413816/

Hysteresis of the Lower Esophageal Sphincter Atropine, which ablates active smooth muscle contraction, had no effect on the DI value. Type 1 esophageal achalasia patients and those with ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/6772120/

Vigorous achalasia. Manometric response to atropine and ... A patient with vigorous achalasia demonstrated manometric response to administration of atropine sulfate and nitroglycerin.

3. journals.physiology.org journals.physiology.org/doi/10.1152/ajpgi.00089.2025

Hysteresis of the lower esophageal sphincter: relevance to ... A low DI following atropine suggests that the passive elements (viscoelastic properties) of EGJ are an important cause of low DI in esophageal achalasia.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S014979440200658X

Achalasia: a brief review of treatment options and efficacy Studies of patients with achalasia note that the most common presenting symptoms include dysphagia (82% to 100%), regurgitation (56% to 97%), weight loss (30% ...

5. link.springer.com link.springer.com/article/10.1007/s12019-002-0038-4

Achalasia: A review of therapeutic options and outcomes This review will focus on methodology and outcomes of two established techniques; pneumatic dilation and surgical myotomy; and one new technique, LES injection ...

6. cdnsciencepub.com cdnsciencepub.com/doi/10.1139/y68-039

The effect of atropine on the gastroesophageal sphincter The higher dosage of atropine caused a significant reduction in the mean maximum pressure in the sphincter both under resting conditions and during abdominal ...

7. chemm.hhs.gov chemm.hhs.gov/countermeasure_atropine-sulfate.htm

Atropine Sulfate - Medical Countermeasures Database Central effects include altered behavior and mental status, loss of consciousness, seizures, or apnea. Most deaths are due to respiratory failure. Treatment ...