# PREcision MEDicine In Achalasia--PREMEDIA

> **NIH NIH U34** · NORTHWESTERN UNIVERSITY · 2023 · $389,578

## Abstract

PROJECT SUMMARY/ABSTRACT
An interruption in the normal swallowing mechanism due to abnormal neuromuscular function in the esophageal
body or the lower esophageal sphincter (LES) is associated with significant morbidity and quality of life impact,
as well as increased mortality related to malnutrition, aspiration and cancer. Achalasia is the prototypical
esophageal motility disorder and has an incidence of 1-5 per 100,000 and a prevalence of 10-20 per 100,000.
Unfortunately, the cause of achalasia is unknown and the current therapies are primarily compensatory in nature
and focus on disrupting the LES to improve emptying using either endoscopic dilation or surgical myotomy. Over
the last 5 years, there has been an evolution away from dilation and surgery toward per oral endoscopic myotomy
(POEM) due to its less invasive approach compared to surgery and its superior efficacy compared to dilation.
 However, important questions regarding the effectiveness and risks of POEM remain and the impact of
the myotomy approach (position, length, depth) on outcomes is also unclear. The standard POEM myotomy is
typically 8-10 cm in length, extending 2-3 cm into the cardia and approximately 6-7 cm above the
squamocolumnar junction and it is performed with either a transmural or superficial approach targeting only the
circular muscle. We recently reported that blown out myotomy (BOM) is a common mechanism of achalasia
treatment failure related to focal dilatation along the myotomy site that profoundly impairs emptying. The
scientific premise of this study is that the current arbitrary approach to myotomy in POEM is associated with a
predilection to increased GERD and BOM formation through its effects on the distal esophagus. We hypothesize
that an innovative precision approach with POEM can improve outcomes and reduce complications. Thus, we
are proposing a multicenter randomized trial (Aim 1) to test the hypothesis that a short, tailored POEM will be
non-inferior to the standard POEM and associated with less reflux disease and a reduction in BOM formation.
Additionally, we will also aim to better understand outcomes in jackhammer esophagus and spastic motility
disorders through a rigorous prospective study (Aim 2) assessing response to a long tailored myotomy. Using
data and samples from study participants, we also aim to refine and validate a new Achalasia Patient Reported
Outcome (APRO) measure (Aim 3) and establish a repository of biological specimens to help elucidate the
pathophysiology of achalasia. This study will reshape the management of esophageal motility disorders and
improve our understanding of the pathogenesis of these disorders by sharing specimens with translational
scientists focused on neurogastroenterology.

## Key facts

- **NIH application ID:** 10722321
- **Project number:** 1U34DK136922-01
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** JOHN E PANDOLFINO
- **Activity code:** U34 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $389,578
- **Award type:** 1
- **Project period:** 2023-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10722321

## Citation

> US National Institutes of Health, RePORTER application 10722321, PREcision MEDicine In Achalasia--PREMEDIA (1U34DK136922-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10722321. Licensed CC0.

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