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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| buspirone | Experimental | 4-weeks buspirone administration (20mg) in patients with SSc and esophageal involvement |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| buspirone | Drug | buspirone 10 mg X2 for 4 weeks |
|
|
| Measure | Description | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | before and after 4 weeks buspirone administration |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Georgios Karamanolis | Academic Department of Gastroenterology, Laikon GH | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Academic Department of Gastroenterology, Laikon GH | Athens | 11527 | Greece |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27586891 | Derived | Karamanolis GP, Panopoulos S, Denaxas K, Karlaftis A, Zorbala A, Kamberoglou D, Ladas SD, Sfikakis PP. The 5-HT1A receptor agonist buspirone improves esophageal motor function and symptoms in systemic sclerosis: a 4-week, open-label trial. Arthritis Res Ther. 2016 Sep 1;18(1):195. doi: 10.1186/s13075-016-1094-y. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Buspirone | Participants received buspirone 20 mg/day for 4 weeks |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Buspirone | 22 out of 30 participants (19 female) completed the study. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | Posted | Mean | Standard Deviation | mmHg | before and after 4 weeks buspirone administration |
|
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Buspirone | Participants received bouspirone 20 mg/day for 4 weeks |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| dizziness | Ear and labyrinth disorders |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. George P. Karamanolis | Academic Department of Gastroenterology, "LAIKON" General Hospital | +30.213.2061307 | georgekaramanolis@yahoo.co.uk |
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| ID | Term |
|---|---|
| D012595 | Scleroderma, Systemic |
| ID | Term |
|---|---|
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D012871 | Skin Diseases |
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| ID | Term |
|---|---|
| D002065 | Buspirone |
| ID | Term |
|---|---|
| D013141 | Spiro Compounds |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
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| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| Primary | Changes From Baseline in Manometric Parameters: Duration of Contractions at the Distal Part of the Esophagus at Week 4 | Posted | Mean | Standard Deviation | sec | before and after 4 weeks buspirone administration |
|
|
|
| Primary | Changes From Baseline in Manometric Parameters: Velocity of Contractions at the Distal Part of the Esophagus at Week 4 | Posted | Mean | Standard Deviation | cm/sec | before and after 4 weeks buspirone administration |
|
|
|
| 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. | Posted | Mean | Standard Deviation | units on a scale | before and after 4 weeks buspirone administration |
|
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|
|
| 0 |
| 30 |
| 4 |
| 30 |
| nausea | Gastrointestinal disorders |
|
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| D010879 |
| Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011743 | Pyrimidines |
| D011083 | Polycyclic Compounds |
| Title | Measurements |
|---|
|
| chest pain |
|