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

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).

Study Overview

• Status: Completed
• Conditions: Systemic Sclerosis
• Intervention / Treatment: Drug: buspirone

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 Type: Interventional
• Enrollment (Actual): 22
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Greece
  • Athens, Greece, 11527
    • Academic Department of Gastroenterology, Laikon GH

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• SSc patients with esophageal symptoms

Exclusion Criteria:

• none

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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 Names: bespar

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Laikο General Hospital, Athens
• Investigators: Principal Investigator: Georgios Karamanolis, Academic Department of Gastroenterology, Laikon GH

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: January 29, 2015
• First Submitted That Met QC Criteria: February 13, 2015
• First Posted (Estimate): February 16, 2015

Study Record Updates

• Last Update Posted (Estimate): October 24, 2016
• Last Update Submitted That Met QC Criteria: August 31, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Connective Tissue Diseases; Sclerosis; Scleroderma, Systemic; Scleroderma, Diffuse; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Serotonin Receptor Agonists; Anti-Anxiety Agents; Buspirone
• Other Study ID Numbers: Laikon 181/21-02-2014