Buspirone for Weak or Absent Esophageal Peristalsis

Dysphagia, Esophageal Clinical Trial

Official title:

The Effect of Oral Buspirone Hydrochloride on Esophageal Motility, Bolus Transit and Symptoms of Dysphagia, in Patients With Poor Esophageal Motility: A Randomized, Double-blind, Placebo Controlled, Cross-over Trial With HRiM

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05629325
• Other study ID #: S62876
• Status: Recruiting
• Phase: Phase 4
• Start date: July 6, 2021
• Est. completion date: September 30, 2024

Study information

• Verified date: November 2022
• Source: Universitaire Ziekenhuizen KU Leuven
• Contact: Jan Tack
• Phone: +3216345514
• Email: jan.tack[@]kuleuven.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomized, double-blind, placebo-controlled, cross-over clinical trial of buspirone in patients with complaints of dysphagia due to poor esophageal motility. The goal of this clinical trial is to study the effect of buspirone on esophageal motility by performing high resolution impedance manometry (HRiM).

Description:

Esophageal motility disorders can be characterized by poor esophageal motility with impaired clearance of the esophagus. Examples are Ineffective Esophageal Motility (IEM, >70% of the swallows are ineffective or ≥50% are failed) and Absent Contractility (100% failed peristalsis). Both might be the underlying cause for dysphagia.

Several studies have shown that poor esophageal motility can be manipulated by pharmacological means. Buspirone, a 5-HT1A agonist, is able to significantly increase distal esophageal wave amplitude and duration in healthy volunteers, suggesting it may be effective in IEM. At the moment, findings in patients with IEM are not consistent and depend on the dose and treatment duration.

This cross-over trial will examine the use of buspirone in patients with dysphagia, with the intent of using a higher dose. We will use impedance/manometry and pressure flow analysis to liquid, viscous and solid boluses to evaluate the symptomatic and manometric effect of buspirone.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 25
• Est. completion date: September 30, 2024
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Patients can participate in this study if:

1. A minimum of 18 years old;

2. Ineffective Esophageal Motility (IEM) or absent contractility, as determined on HRM in the last three months before inclusion in the study, using the Chicago classification v4.0 (1).

IEM is defined as >70% ineffective or =50% failed swallows with a normal integrated relaxation pressure (IRP4). IEM includes a weak contraction (DCI = 100 mmHg·s·cm and <450 mmHg·s·cm), failed peristalsis (DCI < 100 mmHg·s·cm), or fragmented peristalsis (a large break (>5 cm length) in the 20-mmHg isobaric contour with DCI > 450 mmHg·s·cm).

Absent contractility is defined as 100% failed swallows (DCI < 100 mmHg·s·cm), with a normal IRP4.

3. Have completed a gastro-duodenoscopy, within 12 months, showing no anatomical abnormality of the stomach or esophagus, which can explain the patients' symptoms.

4. History of dysphagia for at least 2 months, at least twice per week in the last month.

5. Sexually active women of childbearing potential participating in the study must be using an appropriate form of contraception. Medically acceptable forms of contraception include oral contraceptives, injectable or implantable methods, intrauterine devices, or properly used barrier contraception. If the female patient has not been on oral, injectable, implantable or intrauterine contraception, a urinary pregnancy test will be performed prior to administration of Buspirone/Placebo.

6. Subjects must be capable of understanding and be willing to provide signed and dated written voluntary informed consent before any protocol-specific screening procedures are performed.

Exclusion Criteria:

Patients cannot participate in this study if:

1. Endoscopic signs of severe erosive esophagitis (grade C or D, Los Angeles classification) on endoscopy performed off PPI treatment in the 12 months prior to screening, or = grade B when endoscopy is performed during PPI treatment.

2. Systemic diseases, known to affect esophageal motility (i.e. systemic sclerosis)

3. Surgery in the thorax or in the upper part of the abdomen (appendectomy and cholecystectomy are allowed).

4. Hiatal hernia =3 cm

5. QT c>450 ms.

6. Use of medication that effect cholinergic function such as anticholinergics, tricyclic antidepressants.

7. Concomitant promotility agents such as prucalopride or domperidone.

8. Concomitant use of more than one benzodiazepine.

9. Significant neurological, respiratory, hepatic, renal, hematological, cardiovascular, metabolic or gastrointestinal cerebrovascular disease as judged by the investigator.

10. Major psychiatric disorder.

11. Pregnancy or breastfeeding.

12. History of poor compliance.

13. History of/or current psychiatric illness that would interfere with ability to comply with protocol requirements or give informed consent.

14. History of alcohol or drug abuse that would interfere with ability to comply with protocol requirements.

Related Conditions & MeSH terms

• Deglutition Disorders
• Dysphagia, Esophageal

Intervention

Drug:
• Buspirone Hydrochloride 10 MG
4 weeks of treatment with buspirone
• Placebo
4 weeks of treatment with placebo

Locations

Country	Name	City	State
Belgium	University Hospitals Leuven	Leuven	Vlaams-Brabant

Sponsors (1)

Lead Sponsor	Collaborator
Universitaire Ziekenhuizen KU Leuven

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HRiM Manometric Features: DCI 5ml supine	Changes in distal contractile integral (DCI, in mmHg*s*cm) between buspirone and placebo. DCI is established on HRiM. As primary endpoint, we will focus on the values for DCI for the liquid bolus, 5 ml in supine position.	During manometric assessment after 4 weeks of treatment
Secondary	Bolus passage score	Patients will evaluate the perception of each swallow during the manometric assessment via the following Likert score: 1-Normal, 2-Slow passage of bolus, 3-Stepwise passage, 4-Partial Blockage, 5-Complete Blockage.	During manometric assessment after 4 weeks of treatment
Secondary	HRiM Manometric Features: PCI	Pharyngeal Esophageal Contractile Integral (PCI es., mm.Hg.s.cm)	During manometric assessment after 4 weeks of treatment
Secondary	HRiM Manometric Features: DCI	Distal Esophageal Contractile Integral (DCI, mmHg.s.cm)	During manometric assessment after 4 weeks of treatment
Secondary	HRiM Manometric Features: Largest Break Size	Largest Break Size (cm)	During manometric assessment after 4 weeks of treatment
Secondary	HRiM Manometric Features: DL	Distal Latency (DL, s)	During manometric assessment after 4 weeks of treatment
Secondary	HRiM Manometric Features: IRP4s	Integrated Relaxation Pressure EGJ 4sec (IRP4s, mmHg)	During manometric assessment after 4 weeks of treatment
Secondary	HRiM Manometric Features: PFI	Pressure Flow Index (PFI, -)	During manometric assessment after 4 weeks of treatment
Secondary	HRiM Manometric Features: IR	Impedance Ratio (IR, -)	During manometric assessment after 4 weeks of treatment
Secondary	HRiM Manometric Features: DPA	Distension Pressure Accommodation Phase (DPA, mmHg)	During manometric assessment after 4 weeks of treatment
Secondary	HRiM Manometric Features: DPE	Distension Pressure Emptying Phase (DPE, mmHg)	During manometric assessment after 4 weeks of treatment
Secondary	HRiM Manometric Features: RP	Distal Ramp Pressure (RP, mmHg/s)	During manometric assessment after 4 weeks of treatment
Secondary	HRiM Manometric Features: CSI	Contractile Segment Impedance (CSI, Ohm)	During manometric assessment after 4 weeks of treatment
Secondary	HRiM Manometric Features: BPT	Bolus Presence Time (BPT, s)	During manometric assessment after 4 weeks of treatment
Secondary	HRiM Manometric Features: BFT	Bolus Flow Time (BFT, s)	During manometric assessment after 4 weeks of treatment
Secondary	HRiM Manometric Features: EGJ Rest.P	EGJ Resting Pressure (EGJ Rest.P, mmHg)	During manometric assessment after 4 weeks of treatment
Secondary	HRiM Manometric Features: EGJCI	EGJ Contractile Integral (EGJCI, mmHg.cm)	During manometric assessment after 4 weeks of treatment
Secondary	HRiM Manometric Features: LES-CD	Lower Esophageal Sphincter - Crural Diaphragm (LES-CD, mm)	During manometric assessment after 4 weeks of treatment
Secondary	Mayo Dysphagia Questionnaire	Symptom questionnaire	At baseline and after 4 weeks of treatment
Secondary	Overall Treatment Evaluation (OTE)	Symptoms questionnaire	At baseline and after 4 weeks of treatment
Secondary	Overall Symptom Severity (OSS)	Symptom questionnaire	At baseline and after 4 weeks of treatment