Long Term Effect of Buspirone on Esophageal Function and Esophageal Symptoms in Patients With Systematic Sclerosis (SSc)

• ClinicalTrials.gov Identifier: NCT02363478
• Recruitment Status: Completed
• First Posted: February 16, 2015
• Results First Posted: October 24, 2016
• Last Update Posted: October 24, 2016
• Sponsor: Laikο General Hospital, Athens
• Information provided by (Responsible Party): Assist. Profesor George Karamanolis, Laikο General Hospital, Athens

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Systemic Sclerosis	Drug: buspirone	Early Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 22 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Long Term Effect of Buspirone on Esophageal Function and Esophageal Symptoms in Patients With Systematic Sclerosis (SSc)
• Study Start Date: December 2014
• Actual Primary Completion Date: September 2015
• Actual Study Completion Date: September 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: buspirone; 4-weeks buspirone administration (20mg) in patients with SSc and esophageal involvement	Drug: buspirone; buspirone 10 mg X2 for 4 weeks; Other Name: bespar

Outcome Measures

Primary Outcome Measures :

1. 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 ]
2. 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 ]
3. 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 ]

Secondary Outcome Measures :

1. Changes in the Severity of Esophageal Symptoms at Week 4 [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• SSc patients with esophageal symptoms

Exclusion Criteria:

• none

Contacts and Locations

Locations

Greece

Academic Department of Gastroenterology, Laikon GH

Athens, Greece, 11527

Sponsors and Collaborators

Laikο General Hospital, Athens

Investigators

• Principal Investigator: Georgios Karamanolis; Academic Department of Gastroenterology, Laikon GH

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Assist. Profesor George Karamanolis, Assistant Professor in Gastroenterology, Laikο General Hospital, Athens
• ClinicalTrials.gov Identifier: NCT02363478
• Other Study ID Numbers: Laikon 181/21-02-2014
• First Posted: February 16, 2015
• Results First Posted: October 24, 2016
• Last Update Posted: October 24, 2016
• Last Verified: August 2016

Additional relevant MeSH terms:

Scleroderma, Systemic; Scleroderma, Diffuse; Sclerosis; Pathologic Processes; Connective Tissue Diseases; Skin Diseases; Buspirone; Anti-Anxiety Agents; Tranquilizing Agents; Central Nervous System Depressants; Physiological Effects of Drugs; Psychotropic Drugs; Serotonin Receptor Agonists; Serotonin Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action