Characterization of Antibacterial Antibodies in Patients With Cystic Fibrosis

Identification and Characterization of Antibacterial Antibodies in Sera of Patients With Cystic Fibrosis

Most of the cystic fibrosis (CF) patients are or have been pulmonary colonized with bacteria such as Pseudomonas aeruginosa or Staphylococcus aureus. Aim of this study is to detect virulence factor neutralizing antibodies in the sera of the study population followed by B cell repertoire analyses to design B cell-derived neutralizing monoclonal antibodies. The functionality of neutralizing antibodies rests on inhibition of virulence factors by binding of crucial epitopes rather than merely the induction of opsonization. Focusing on patients with bacterial colonization/chronic infections or a history of an acute infection in the past, will increase the likelihood for identification of serum with neutralizing activity as in vivo antigen contact is a prerequisite for antibody development and maturation. Since virulence factors are essential for infection, dissemination and tissue damage, inhibition of these factors by developed neutralizing antibodies might contribute to a favorable outcome of life-threatening infections.

Study Overview

• Status: Recruiting
• Conditions: Pulmonary Cystic Fibrosis; Neutralizing Antibodies
• Intervention / Treatment: Other: Blood sampling

• Study Type: Observational
• Enrollment (Anticipated): 75

Contacts and Locations

• Study Contact: Name: Alexander Simonis; Phone Number: +4922147889608; Email: alexander.simonis@uk-koeln.de

Study Locations

• Germany
  • Cologne, Germany
    • Recruiting
    • CF Study Center, University Hospital Cologne
    • Contact: Silke van Koningsbruggen-Rietschel, MD, PhD
    • Principal Investigator: Silke van Koningsbruggen-Rietschel, MD, PhD
    • Principal Investigator: Ernst Rietschel, MD
    • Principal Investigator: Jan Rybniker, MD, PhD
    • Principal Investigator: Alexander Simonis, MD

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients of the University Hospital Cologne

Description

Inclusion Criteria:

• Age ≥ 18 years
• Ability to give consent
• Normal vital signs including:
• Blood pressure systolic value 150 - 100 mmHg, diastolic value < 90 mmHg
• Respiratory rate < 20/min
• Oxygen saturation >92%
• Heart rate 50 - 110/min
• Body temperature <38°C

Exclusion Criteria:

• Cytopenia (leukocytes < 1.500/µl, thrombocytes < 50.000/µl, Hemoglobin < 12 g/dl)
• Heart disease or pulmonary hypertension
• Body weight <50 kg (exclusion of blood sampling for B cell isolation)
• Blood donation, larger blood loss and/or major surgery in the last 8 (male) or 12 (female) weeks
• Any decline of the general state of health in the last 3 month including weight loss > 2kg, pulmonal exacerbation or increased impairment of pulmonary function (FEV1 < 50%)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with Cystic Fibrosis; Patients with pulmonary Cystic Fibrosis with or without bacterial colonization	Other: Blood sampling; Screening: Blood sampling of 15 ml whole blood B cell isolation: Blood sampling of max. 400 ml whole blood or 6% of the total blood volume (♀ 65 ∓ 10 ml/kg; ♂ 77 ∓ 10 ml/kg)
Control group; Healthy age- and sex-matched controls including healthy individuals and patients with acute or chronic bacterial infections	Other: Blood sampling; Screening: Blood sampling of 15 ml whole blood B cell isolation: Blood sampling of max. 400 ml whole blood or 6% of the total blood volume (♀ 65 ∓ 10 ml/kg; ♂ 77 ∓ 10 ml/kg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Prevalence of antibacterial antibodies	3 years

Collaborators and Investigators

• Sponsor: University Hospital of Cologne
• Investigators: Study Director: Silke van Koningsbruggen-Rietschel, MD, PhD, University Hospital Cologne; Study Director: Jan Rybniker, MD, PhD, University Hospital Cologne

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2020
• Primary Completion (Anticipated): September 30, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: January 6, 2021
• First Submitted That Met QC Criteria: January 6, 2021
• First Posted (Actual): January 7, 2021

Study Record Updates

• Last Update Posted (Actual): January 7, 2021
• Last Update Submitted That Met QC Criteria: January 6, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: 20-1287_1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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