Buspirone for Weak or Absent Esophageal Peristalsis

NCT05629325 | Recruiting Phase 4

• 1 other identifier: S62876
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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).

Conditions

Dysphagia, Esophageal

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (20)

• Bolus passage score

  During manometric assessment after 4 weeks of treatment

• HRiM Manometric Features: PCI

  During manometric assessment after 4 weeks of treatment

• HRiM Manometric Features: DCI

  During manometric assessment after 4 weeks of treatment

• HRiM Manometric Features: Largest Break Size

  During manometric assessment after 4 weeks of treatment

• HRiM Manometric Features: DL

  During manometric assessment after 4 weeks of treatment

Study Arms (2)

Buspirone => Washout => Placebo

EXPERIMENTAL

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.

Drug: Buspirone Hydrochloride 10 MG; Drug: Placebo

Placebo => Washout => Buspirone

EXPERIMENTAL

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.

Drug: Buspirone Hydrochloride 10 MG; Drug: Placebo

Interventions

Buspirone Hydrochloride 10 MG DRUG

4 weeks of treatment with buspirone

Also known as: Buspiron

Buspirone => Washout => Placebo; Placebo => Washout => Buspirone

Placebo DRUG

4 weeks of treatment with placebo

Buspirone => Washout => Placebo; Placebo => Washout => Buspirone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients can participate in this study if:
• A minimum of 18 years old;
• 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.
• Have completed a gastro-duodenoscopy, within 12 months, showing no anatomical abnormality of the stomach or esophagus, which can explain the patients' symptoms.
• History of dysphagia for at least 2 months, at least twice per week in the last month.
• 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.
• 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.

You may not qualify if:

• Patients cannot participate in this study if:
• 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.
• Systemic diseases, known to affect esophageal motility (i.e. systemic sclerosis)
• Surgery in the thorax or in the upper part of the abdomen (appendectomy and cholecystectomy are allowed).
• Hiatal hernia ≥3 cm
• QT c\>450 ms.
• Use of medication that effect cholinergic function such as anticholinergics, tricyclic antidepressants.
• Concomitant promotility agents such as prucalopride or domperidone.
• Concomitant use of more than one benzodiazepine.
• Significant neurological, respiratory, hepatic, renal, hematological, cardiovascular, metabolic or gastrointestinal cerebrovascular disease as judged by the investigator.
• Major psychiatric disorder.
• Pregnancy or breastfeeding.
• History of poor compliance.
• History of/or current psychiatric illness that would interfere with ability to comply with protocol requirements or give informed consent.
• History of alcohol or drug abuse that would interfere with ability to comply with protocol requirements.

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead

Study Sites (1)

University Hospitals Leuven

Leuven, Vlaams-Brabant, 3000, Belgium

RECRUITING

MeSH Terms

Conditions

Deglutition Disorders

Interventions

Buspirone

Condition Hierarchy (Ancestors)

Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Pharyngeal Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Spiro Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Polycyclic Compounds

Study Officials

• Jan Tack

  UZ Leuven

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jan Tack

CONTACT

+3216345514; jan.tack@kuleuven.be

KU Leuven

CONTACT

+3216320429; marthe.everaert@kuleuven.be

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: A randomization list will be prepared by the laboratorium Wolfs (Zwijndrecht, Belgium) and the trial medication will be labeled by the laboratorium Wolfs based on the randomization list. The randomization list is prepared separately from study investigators or coordinators. The participant, investigator and study team are blinded to the allocated treatment arm in both intervention periods (buspirone/placebo). Each study patient will be assigned a subsequent randomization number. If a medical emergency occurs and a decision about the subject's condition requires knowledge of the treatment assignment, the investigator will immediately notify the laboratorium Wolfs to break the blind for this individual subject.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: November 8, 2022
• First Posted: November 29, 2022
• Study Start: July 6, 2021
• Primary Completion: September 30, 2024
• Study Completion: September 30, 2024
• Last Updated: July 3, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)