Buspirone for Weak or Absent Esophageal Peristalsis

NCT ID: NCT05629325

Last Updated: 2024-07-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-06
• Study Completion Date: 2024-09-30

Brief 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).

Detailed 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.

Conditions

Dysphagia, Esophageal

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Buspirone => Washout => Placebo

Patients will take Buspirone hydrochloride 10mg oral once a day (in the evening) for 3 days, twice a day (morning and evening) for 4 days, three times a day for 2 weeks and 20mg oral three times a day for one week. Esophageal motility will be assessed with high resolution impedance manometry (HRiM) after 4 weeks of treatment. Patients will also report their perceived symptoms of dysphagia during the HRiM. A washout period of two weeks will take place. Afterwards, the second treatment period starts. Patients will take Placebo oral once a day (in the evening) for 3 days, twice a day (morning and evening) for 4 days, three times a day for 2 weeks and 20mg oral three times a day for one week. Esophageal motility will also be assessed with high resolution impedance manometry (HRiM) after 4 weeks of treatment. Patients will again report their perceived symptoms of dysphagia during the HRiM.

Group Type: EXPERIMENTAL

Buspirone Hydrochloride 10 MG

Intervention Type: DRUG

4 weeks of treatment with buspirone

Placebo

Intervention Type: DRUG

4 weeks of treatment with placebo

Placebo => Washout => Buspirone

Patients will take Placebo oral once a day (in the evening) for 3 days, twice a day (morning and evening) for 4 days, three times a day for 2 weeks and 20mg oral three times a day for one week. Esophageal motility will be assessed with high resolution impedance manometry (HRiM) after 4 weeks of treatment. Patients will also report their perceived symptoms of dysphagia during the HRiM. A washout period of two weeks will take place. Afterwards, the second treatment period starts. Patients will take Buspirone hydrochloride oral once a day (in the evening) for 3 days, twice a day (morning and evening) for 4 days, three times a day for 2 weeks and 20mg oral three times a day for one week. Esophageal motility will also be assessed with high resolution impedance manometry (HRiM) after 4 weeks of treatment. Patients will again report their perceived symptoms of dysphagia during the HRiM.

Group Type: EXPERIMENTAL

Buspirone Hydrochloride 10 MG

Intervention Type: DRUG

4 weeks of treatment with buspirone

Placebo

Intervention Type: DRUG

4 weeks of treatment with placebo

Interventions

Buspirone Hydrochloride 10 MG

4 weeks of treatment with buspirone

Intervention Type: DRUG

Placebo

4 weeks of treatment with placebo

Intervention Type: DRUG

Other Intervention Names

Buspiron

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Universitaire Ziekenhuizen KU Leuven

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jan Tack

Role: PRINCIPAL_INVESTIGATOR

UZ Leuven

Locations

University Hospitals Leuven

Leuven, Vlaams-Brabant, Belgium

Site Status: RECRUITING

Countries

Belgium

Central Contacts

Jan Tack

Role: CONTACT

jan.tack@kuleuven.be

+3216345514

KU Leuven

Role: CONTACT

marthe.everaert@kuleuven.be

+3216320429

Facility Contacts

Jan Tack, M.D., Ph.D.

Role: primary

jan.tack@kuleuven.be

+3216345514

Other Identifiers

S62876

Identifier Type: -

Identifier Source: org_study_id