Pilot Study for Cell Based Therapies in Patients With Asthma

Development and Validation of Magnetic Cell Separations Techniques Using a Good Manufacturing Practice (GMP) Grade Manufacturing Process for Clinical Applications and Generation of Pre-clinical Data

The aim of this study is to investigate the immunomodulatory potential of Isolated Plasmacytoide Dendritic Cells (pDCs) and Regulatory T-cells (TREGs) isolated with clinical grade magnetic bead isolations techniques (MACS®) on the antigen presenting cell-induced proliferation of lymphocytes after allergen uptake in an in vitro cell culture system.

Study Overview

• Status: Completed
• Conditions: Asthma; Allergic Rhinitis
• Intervention / Treatment: Other: Blood donation

Detailed Description

pDCs as well as TREGs will be co-incubated with generated allergen presenting cells, lymphocytes, and allergen. For in vitro experimentation immune cells will be collected from blood of grass mix or house dust mite sensitized atopic/asthmatic patients.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Male subjects suffering from allergic rhinitis and/or allergic asthma against timothy grass pollen (phleum pratense) and/or house dust mite.
• age 18-60 years,
• Nonsmokers or smokers with a history of less than 1 pack years who have not smoked within the last 12 months.
• Positive skin prick test for timothy grass pollen (phleum pratense) and/or house dust mile within 12 months
• Able and willing to give written informed consent
• Hemoglobin ≥135 g/l
• Hematocrit ≥ 0,40
• Body weight ≥ 50 kg and Body Mass Index (BMI) within the range 19-32 kg/m²

Exclusion Criteria:

• History of lower respiratory tract infection and /or exacerbation of asthma within four weeks prior to the informed consent visit
• Febrile illness within four week before the trial examination
• Administration of oral, injectable, or dermal corticosteroids within the last 8 weeks or intranasal and/or inhaled corticosteroids within the last 4 weeks.
• Intake of methylxanthines, antihistamines, antileukotrienes, oral cromolyn sodium, or oral nedocromil sodium
• Past or present disease, which as judged by the investigator, may affect the outcome of this trial. These diseases include, but are not limited to, cardiovascular disease, malignancy, hepatic disease, renal disease, hematological disease, neurological disease, endocrine disease, or pulmonary disease (including but not confined to chronic bronchitis, emphysema, tuberculosis, bronchiectasis or cystic fibrosis).
• Specific immunotherapy (SIT) within the last two years prior to screening
• Participation in another clinical trial 30 days prior to enrollment
• Donation of more than 500 ml of blood in the preceding 9 weeks before the trial-examination
• Hemoglobin below the normal lower limit
• History of drug and/or alcohol abuse or dependence within 12 months of the trial
• Risk of non-compliance with trial procedures
• Suspected inability to understand the protocol requirements, instructions and trial-related restrictions, the nature, scope, and possible consequences of the trial
• Patient is tested human immunodeficiency virus (HIV)-1/2Ab, hepatitis B surface antigen (HBsAg), or hepatitis C virus antibodies (HCV-Ab) positive

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)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Blood donation

Other: Blood donation; In experimental part 1 to generate preclinical data 250 ml of blood will be donated at day 1 by 10 subjects to induce allergen presenting cells (APCs). In experimental part 2 to transfer the isolation of pDC or TREGs to a GMP (good manufacturing Practice) compliant clinical grade isolation system, leukapheresis will be performed with the blood from 5 subjects. In experimental part 3 for potency testing of the clinical grade isolation system of pDC or TREGs, 250 ml of blood will be collected at day 1 from 3 subjects.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Purity of MACS® and CliniMacs® BDCA-4 positive isolated plasmcytoid dendritic cells: Percentage of CD123/BDCA-2 expressing cells

Collaborators and Investigators

• Sponsor: Fraunhofer-Institute of Toxicology and Experimental Medicine
• Collaborators: Hannover Medical School
• Investigators: Principal Investigator: Norbert Krug, MD, Fraunhofer Institute for Toxicology and Experimental Medicine

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): November 1, 2011
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: March 12, 2010
• First Submitted That Met QC Criteria: March 15, 2010
• First Posted (Estimate): March 16, 2010

Study Record Updates

• Last Update Posted (Estimate): November 9, 2011
• Last Update Submitted That Met QC Criteria: November 8, 2011
• Last Verified: November 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Otorhinolaryngologic Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Nose Diseases; Asthma; Rhinitis; Rhinitis, Allergic
• Other Study ID Numbers: 09/11 PILOCELL