Clinical trial NCT05629325: Buspirone for Weak or Absent Esophageal Peristalsis
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Dysphagia, Esophageal
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
First posted: 2022-11-29
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Patients with IEM or absent contractility and symptoms of dysphagia will participate in this study. They will be randomized on a 1:1 basis: Patients will be randomized to take buspirone for 4 weeks or placebo for 4 weeks. After a 2-week washout period the randomized groups will cross over into the alternate treatment.
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: HRiM Manometric Features: DCI 5ml supine
timeFrame: During manometric assessment after 4 weeks of treatment
Secondary outcomes:
measure: Bolus passage score
timeFrame: During manometric assessment after 4 weeks of treatment
measure: HRiM Manometric Features: PCI
timeFrame: During manometric assessment after 4 weeks of treatment
measure: HRiM Manometric Features: DCI
timeFrame: During manometric assessment after 4 weeks of treatment
measure: HRiM Manometric Features: Largest Break Size
timeFrame: During manometric assessment after 4 weeks of treatment
measure: HRiM Manometric Features: DL
timeFrame: During manometric assessment after 4 weeks of treatment
measure: HRiM Manometric Features: IRP4s
timeFrame: During manometric assessment after 4 weeks of treatment
measure: HRiM Manometric Features: PFI
timeFrame: During manometric assessment after 4 weeks of treatment
measure: HRiM Manometric Features: IR
timeFrame: During manometric assessment after 4 weeks of treatment
measure: HRiM Manometric Features: DPA
timeFrame: During manometric assessment after 4 weeks of treatment
measure: HRiM Manometric Features: DPE
timeFrame: During manometric assessment after 4 weeks of treatment
measure: HRiM Manometric Features: RP
timeFrame: During manometric assessment after 4 weeks of treatment
measure: HRiM Manometric Features: CSI
timeFrame: During manometric assessment after 4 weeks of treatment
measure: HRiM Manometric Features: BPT
timeFrame: During manometric assessment after 4 weeks of treatment
measure: HRiM Manometric Features: BFT
timeFrame: During manometric assessment after 4 weeks of treatment
measure: HRiM Manometric Features: EGJ Rest.P
timeFrame: During manometric assessment after 4 weeks of treatment
measure: HRiM Manometric Features: EGJCI
timeFrame: During manometric assessment after 4 weeks of treatment
measure: HRiM Manometric Features: LES-CD
timeFrame: During manometric assessment after 4 weeks of treatment
measure: Mayo Dysphagia Questionnaire
timeFrame: At baseline and after 4 weeks of treatment
measure: Overall Treatment Evaluation (OTE)
timeFrame: At baseline and after 4 weeks of treatment
measure: Overall Symptom Severity (OSS)
timeFrame: At baseline and after 4 weeks of treatment
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: University Hospitals Leuven
state: Vlaams-Brabant
Study officials:
affiliation: UZ Leuven
name: Jan Tack
role: PRINCIPAL_INVESTIGATOR
References: