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
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- HRiM Manometric Features: DCI 5ml supine
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients can participate in this study if:
- •A minimum of 18 years old;
- •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 IRP
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Buspirone Hydrochloride 10 MG (Drug)
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.
干预措施: Placebo (Drug)
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.
干预措施: Buspirone Hydrochloride 10 MG (Drug)
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.
干预措施: Placebo (Drug)
结局指标
主要结局
HRiM Manometric Features: DCI 5ml supine
时间窗: During manometric assessment after 4 weeks of treatment
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.
次要结局
- HRiM Manometric Features: PFI(During manometric assessment after 4 weeks of treatment)
- Mayo Dysphagia Questionnaire(At baseline and 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: DPE(During manometric assessment after 4 weeks of treatment)
- HRiM Manometric Features: RP(During manometric assessment after 4 weeks of treatment)
- HRiM Manometric Features: BPT(During manometric assessment after 4 weeks of treatment)
- HRiM Manometric Features: BFT(During manometric assessment after 4 weeks of treatment)
- Overall Treatment Evaluation (OTE)(At baseline and after 4 weeks of treatment)
- Overall Symptom Severity (OSS)(At baseline and after 4 weeks of treatment)
- HRiM Manometric Features: DL(During manometric assessment after 4 weeks of treatment)
- HRiM Manometric Features: LES-CD(During manometric assessment after 4 weeks of treatment)
- HRiM Manometric Features: IRP4s(During manometric assessment after 4 weeks of treatment)
- HRiM Manometric Features: EGJ Rest.P(During manometric assessment after 4 weeks of treatment)
- 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: IR(During manometric assessment after 4 weeks of treatment)
- HRiM Manometric Features: DPA(During manometric assessment after 4 weeks of treatment)
- HRiM Manometric Features: CSI(During manometric assessment after 4 weeks of treatment)
- HRiM Manometric Features: EGJCI(During manometric assessment after 4 weeks of treatment)