Sphingosine-1-phosphate in Asthma

Does Sphingosine-1-phosphate Constrict Human Airways? In-vivo Challenge Pilot Study.

This study is being undertaken in order to enhance our understanding how human airways are being constricted in healthy people and in individuals with asthma. There is an unmet need for identification of new pathways (mediators) related to enhanced constriction of the asthmatic airways that would reveal new targets for therapy. Sphingosine-1-phosphate (S1P) is a naturally occurring bioactive lipid molecule that has been suggested to play an important role in asthma. Physiologically, S1P can be detected in human blood but local tissue concentrations (for example in the lung) are very low. Upon activation many cells can secrete S1P. Increased concentrations of S1P have been detected in airways of asthmatic subjects after allergen inhalation. When studied in animal models, S1P did not cause contraction of airways in healthy animals but contracted airways in animal with pulmonary inflammation. In laboratory experiments S1P has been shown to be a potent constrictor of cells responsible for contraction of human airways. As yet, however, we lack evidence that S1P actually causes constriction of airways in real life. Establishing S1P as a molecule capable of causing airway constriction in humans and perhaps specifically in asthmatics will have important implications for our understanding of physiological and pathophysiological responses in human airways and could open new windows for therapeutic strategies in diseases like asthma.

Study Overview

• Status: Recruiting
• Conditions: Asthma
• Intervention / Treatment: Other: Bronchial challenge test

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Grzegorz Woszczek, MD, PhD; Phone Number: +44 2071880597; Email: grzegorz.woszczek@kcl.ac.uk
• Study Contact Backup: Name: Leonard Siew, MRCP, PhD; Email: leonard.siew@gstt.nhs.uk

Study Locations

• United Kingdom
  • London, United Kingdom, SE1 9RT
    • Recruiting
    • Allergy Day Care Unite, Guy's Hospital
    • Contact: Stephanie Yung, Dr; Phone Number: 020 7188 5846; Email: Stephanie.yung@gstt.nhs.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Cases (asthmatics) inclusion criteria

1. Physician diagnosed asthma, defined as a clear history of typical symptoms and clear reversibility of the PEF/FEV1 (12% or more) within the past year and/or methacholine PC20 < 8mg/ml.

Cases Exclusion criteria

1. Pregnancy or lactation
2. Moderate / Severe asthma (FEV1/PEF < 80%of the predicted value at screening)
3. Patients with any chronic illness other than asthma and other recognised atopic diseases (eczema, rhinitis) or any other abnormality which in the opinion of the principal investigator might compromise the study findings
4. A history of recent (within the past 4 weeks) upper or lower respiratory tract infection
5. Patients receiving oral, inhaled or parenteral glucocorticoid therapy (steroid) within the last 4 weeks, long acting relievers (salmeterol, formoterol) and antileukotrienes (montelukast) within last 72 hours.
6. Inadequate contraception in women of childbearing age
7. Inability to comprehend or comply with the protocol

Controls inclusion criteria

1. Lifelong absence of asthma symptoms and lung function within the normal range.

Controls exclusion criteria

1. Pregnancy or lactation
2. Patients with any chronic illness or any other abnormality which in the opinion of the principal investigator might compromise the study findings
3. A history of recent (within the past 4 weeks) upper or lower respiratory tract infection
4. Oral, inhaled or parenteral glucocorticoid therapy (steroid) within the last 4 weeks, long acting relievers (salmeterol, formoterol) and antileukotrienes (montelukast) within last 72 hours
5. Inadequate contraception in women of childbearing age
6. Inability to comprehend or comply with the protocol

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bronchoconstriction	Bronchoconstriction in response to challenge measured by spirometry (FEV1)(PC20)	1 hour after challenge

Collaborators and Investigators

• Sponsor: Guy's and St Thomas' NHS Foundation Trust
• Collaborators: King's College London
• Investigators: Principal Investigator: Grzegorz Woszczek, MD, PhD, King's College London

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2020
• Primary Completion (Anticipated): February 22, 2022
• Study Completion (Anticipated): February 22, 2022

Study Registration Dates

• First Submitted: October 18, 2019
• First Submitted That Met QC Criteria: October 18, 2019
• First Posted (Actual): October 22, 2019

Study Record Updates

• Last Update Posted (Actual): July 28, 2021
• Last Update Submitted That Met QC Criteria: July 27, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: 223069

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No