Systemic Sclerosis
Conditions
Brief summary
Esophagus is commonly affected in Systemic Sclerosis (SSc) and esophageal function is compromised in about 75% of patients. Previous studies have shown that buspirone, an orally available 5-HT1A (serotonin 1a receptor agonist), enhances esophageal motility in healthy volunteers. Recently, the investigators observed that a single dose of buspirone (10mg) improves lower esophageal sphincter (LES) function in patients with SSc and esophageal involvement . Objectives: To evaluate the effect of continuous administration of buspirone on esophageal dysfunction and related symptoms in SSc using high resolution manometry (HRM).
Detailed description
Systemic sclerosis (SSc) is a chronic autoimmune disease affecting the skin and other organs especially the gastrointestinal tract. Esophageal involvement occurs in up to 90% of SSc patients. Symptoms of esophageal disease are due to gastroesophageal reflux disease (GERD) and esophageal motor dysfunction. Thus, heartburn, regurgitation and dysphagia have been reported by 80% of SSc patients. The gold standard method for the assessment and detection of esophageal dysmotility in SSc patients is manometry. High-resolution manometry (HRM) is the most accurate tool to assess esophageal motility using multiple closely spaced (\<2cm) pressure sensors, assessment of esophageal motility is more sensitive ,and allows a better assessment of LES and of the whole esophagus. Buspirone, an orally available 5-HT1A receptor agonist, exerts a beneficial acute effect on esophageal motor dysfunction and LES pressure and may enhances an important role in improvement of esophageal symptoms in SSc patients. Thus, the investigators will conduct a study to evaluate the putative beneficial long-term effect of buspirone i) on esophageal motor dysfunction and ii) on esophageal symptoms in symptomatic SSc patients.
Interventions
DRUGbuspirone
buspirone 10 mg X2 for 4 weeks
Sponsors
Laikο General Hospital, Athens
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* SSc patients with esophageal symptoms
Exclusion criteria
* none
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Changes From Baseline in Manometric Parameters: i) Amplitude of Contractions at the Distal Part of the Esophagus and ii) Resting and Residual (Lower Esophageal Pressure) LES Pressure and IRP (Integrated Relaxation Pressure) at Week 4 | before and after 4 weeks buspirone administration |
| Changes From Baseline in Manometric Parameters: Duration of Contractions at the Distal Part of the Esophagus at Week 4 | before and after 4 weeks buspirone administration |
| Changes From Baseline in Manometric Parameters: Velocity of Contractions at the Distal Part of the Esophagus at Week 4 | before and after 4 weeks buspirone administration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in the Severity of Esophageal Symptoms at Week 4 | before and after 4 weeks buspirone administration | Severity of esophageal symptoms (dysphagia, heartburn, regurgitation and chest pain) was measured on a 100-point visual analogue scale (VAS) ranging from 0 (absent) to 100 (very severe). Even minor decrease in the VAS score for each symptom at week 4 considered as improvement. |
Countries
Greece
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Buspirone 22 out of 30 participants (19 female) completed the study. | 22 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Lost to Follow-up | 4 |
Baseline characteristics
| Characteristic | Buspirone |
|---|---|
| Age, Continuous | 52.5 years STANDARD_DEVIATION 11.6 |
| Region of Enrollment Greece | 22 participants |
| Sex: Female, Male Female | 19 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 4 / 30 |
| serious Total, serious adverse events | 0 / 30 |
Outcome results
Primary
Changes From Baseline in Manometric Parameters: Duration of Contractions at the Distal Part of the Esophagus at Week 4
Time frame: before and after 4 weeks buspirone administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Buspirone | Changes From Baseline in Manometric Parameters: Duration of Contractions at the Distal Part of the Esophagus at Week 4 | 0.5 sec | Standard Deviation 0.4 |
Primary
Changes From Baseline in Manometric Parameters: i) Amplitude of Contractions at the Distal Part of the Esophagus and ii) Resting and Residual (Lower Esophageal Pressure) LES Pressure and IRP (Integrated Relaxation Pressure) at Week 4
Time frame: before and after 4 weeks buspirone administration
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Buspirone | Changes From Baseline in Manometric Parameters: i) Amplitude of Contractions at the Distal Part of the Esophagus and ii) Resting and Residual (Lower Esophageal Pressure) LES Pressure and IRP (Integrated Relaxation Pressure) at Week 4 | amplitude | 0.9 mmHg | Standard Deviation 0.2 |
| Buspirone | Changes From Baseline in Manometric Parameters: i) Amplitude of Contractions at the Distal Part of the Esophagus and ii) Resting and Residual (Lower Esophageal Pressure) LES Pressure and IRP (Integrated Relaxation Pressure) at Week 4 | LES resting pressure | 4.5 mmHg | Standard Deviation 0.7 |
| Buspirone | Changes From Baseline in Manometric Parameters: i) Amplitude of Contractions at the Distal Part of the Esophagus and ii) Resting and Residual (Lower Esophageal Pressure) LES Pressure and IRP (Integrated Relaxation Pressure) at Week 4 | LES residual pressure | 0.3 mmHg | Standard Deviation 0.2 |
| Buspirone | Changes From Baseline in Manometric Parameters: i) Amplitude of Contractions at the Distal Part of the Esophagus and ii) Resting and Residual (Lower Esophageal Pressure) LES Pressure and IRP (Integrated Relaxation Pressure) at Week 4 | IRP | 0.4 mmHg | Standard Deviation 0.2 |
p-value: <0.05t-test, 2 sided
Primary
Changes From Baseline in Manometric Parameters: Velocity of Contractions at the Distal Part of the Esophagus at Week 4
Time frame: before and after 4 weeks buspirone administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Buspirone | Changes From Baseline in Manometric Parameters: Velocity of Contractions at the Distal Part of the Esophagus at Week 4 | 0.3 cm/sec | Standard Deviation 0.5 |
Secondary
Changes in the Severity of Esophageal Symptoms at Week 4
Severity of esophageal symptoms (dysphagia, heartburn, regurgitation and chest pain) was measured on a 100-point visual analogue scale (VAS) ranging from 0 (absent) to 100 (very severe). Even minor decrease in the VAS score for each symptom at week 4 considered as improvement.
Time frame: before and after 4 weeks buspirone administration
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Buspirone | Changes in the Severity of Esophageal Symptoms at Week 4 | heartburn | 14.9 units on a scale | Standard Deviation 7.8 |
| Buspirone | Changes in the Severity of Esophageal Symptoms at Week 4 | regurgitation | 13.2 units on a scale | Standard Deviation 2.7 |
| Buspirone | Changes in the Severity of Esophageal Symptoms at Week 4 | dysphagia | 6.9 units on a scale | Standard Deviation 8.8 |
| Buspirone | Changes in the Severity of Esophageal Symptoms at Week 4 | chest pain | 1.9 units on a scale | Standard Deviation 3.1 |
p-value: 0.05t-test, 2 sided