Viral Mucosal Reprogramming (VMR)
Primary Purpose
Asthma, Allergic Rhinitis, Cat Allergy
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Research Grade RG-RV
Sponsored by
About this trial
This is an interventional basic science trial for Asthma focused on measuring Asthma, Allergy, Allergic, Rhinitis, Airway, Cat dander, Respiratory
Eligibility Criteria
Inclusion Criteria:
Healthy Normal Control Group
- Subject must be able to understand and provide informed consent
- Age: 18-60 inclusive
- Sex: M or F
- No history of asthma, COPD, rhinitis, or other clinically important respiratory disease
- Non-smoker, or ex-smoker with <10 pack years, at least 5 years remote.
- No history of diabetes or cardiovascular disease
- Negative ImmunoCAP test to regionally relevant allergen panel obtained at Screening. Alternatively, documented history of a negative skin test or negative specific IgE obtained within the past 12 months.
Allergic Rhinitis Group
- Subject must be able to understand and provide informed consent
- Age: 18-60 inclusive
- Sex: M or F
- No history of asthma, COPD, or other clinically important respiratory disease
- Non-smoker, or ex-smoker with <10 pack years, at least 5 years remote
- No history of diabetes or cardiovascular disease
- History of rhinitis, physician diagnosed, plus one of the following criteria within the past 12 months
- Seasonal or perennial nasal congestion or sneezing
- Seasonal or perennial conjunctival infection or watering
- No evidence of airway obstruction (FEV1:FVC ≥ lower limit of normal)
- Positive ImmunoCAP test to cat. Documented history at any time of a positive skin test or a specific IgE measure at least Level 2 reactivity will meet this criterion. Subjects must have cat in home, have regular exposure to cat dander, or live in a home where a cat has lived within the past 6 months.
Allergic Asthma Group
Inclusion Criteria
- Subject must be able to understand and provide informed consent
- Age: 18-60 inclusive
- Sex: M or F
- No history of COPD or other clinically important respiratory disease other than asthma
- Non-smoker, or ex-smoker with <10 pack years, at least 5 years remote
- No history of diabetes or cardiovascular disease
History of mild-moderate asthma, physician diagnosed, plus one of the following criteria within the past 12 months
- Airway obstruction (FEV1: FVC <0.6) that is significantly (at least 12% change from baseline, ATS criteria) reversible after 4 puffs of albuterol (obtained at Screening Visit or documented historical testing performed with the past 12 months)
- Requiring ICS for control of asthma for at least 30 days within the past 12 months
- Positive ImmunoCAP test to cat dander. Documented history at any time of a positive skin test or a specific IgE measure at least Level 2 reactivity will meet this criteria. Subjects must have cat in home, have regular exposure to cat dander, or live in a home where a cat has lived within the past 6 months.
- Results of the CBC do not show clinically important abnormalities
Exclusion Criteria:
Healthy Group Normal Group
- Inability or unwillingness of a participant to comply with study protocol
- Currently taking inhaled corticosteroids, leukotriene modifier, or antihistamines for respiratory disease.
- Neutralizing Ab to RV16 greater than or equal to 1:8
- Pregnant or breastfeeding women or a woman who has a planned pregnancy during the course of the study. Menstruating females must have a negative pregnancy test at the screening visit. Pregnancy testing may be conducted prior to procedures as well at various times in the study.
- Subjects with household or close contacts who are pregnant or planning a pregnancy during the main subject's participation, who have chronic respiratory disease, who are children under the age of 2 years, or who are adults over 60 years of age or are Immunosuppressed e.g. post-chemotherapy, HIV).
- Subjects who provide healthcare services or work with elderly or children (e.g. daycare provider, senior citizen care giver).
Allergic Rhinitis Group
- Inability or unwillingness of a participant to comply with study protocol
- Currently using inhaled steroids, or oral montelukast for respiratory disease
- Neutralizing Ab to RV16 greater than or equal to 1:8
- Pregnant or breastfeeding women or a woman who has a planned pregnancy during the course of the study. Menstruating females must have a negative pregnancy test at screening visit. Pregnancy testing may be conducted prior to procedures as well at various times in the study.
- Subjects with household or close contacts who are pregnant or planning a pregnancy during the main subject's participation, who have chronic respiratory disease, who are children under the age of 2 years, or who are adults over 60 years of age or are Immunosuppressed e.g. post-chemotherapy, HIV) .
- Subjects who provide healthcare services or work with elderly or children (e.g. daycare provider, senior citizen care giver).
- Subjects who have received immunosuppressive treatment within the last 12 months
- BMI is greater than 35
- History of symptoms consistent with a viral URI within the past 21 days
- Results of the CBC do not show clinically important abnormalities
- Family history or medical history of liver disease or bleeding disorders
- Have not received systemic corticosteroids for 3months prior to Screening
- Antiplatelet agents other than aspirin
- Subjects who have a positive COVID-19 test will be excluded for 8 weeks
Allergic Asthma Group
- Inability or unwillingness of a participant to comply with study protocol
- Currently taking medications for respiratory diseases other than ICS, montelukast, or rescue albuterol or LABAs.
- Neutralizing Ab to RV16 greater than or equal to 1:8
- FEV1: FVC ratio less than 0.6, or FEV1 less than 60% predicted
- Recent (<30 days) exacerbation of asthma requiring systemic corticosteroids
- ICS greater than fluticasone 500 mcg/day or its equivalent (GINA 2019 table) at screening.
- Pregnant or breastfeeding women or a woman who has a planned pregnancy during the course of the study. Menstruating females must have a negative pregnancy test at screening. Pregnancy testing may be conducted prior to procedures as well at various times in the study.
- Subjects with household or close contacts who are pregnant or planning a pregnancy during the main subject's participation, who have chronic respiratory disease, who are children under the age of 2 years, or who are adults over 60 years of age or are Immunosuppressed e.g. post-chemotherapy, HIV) .
- Subjects who provide healthcare services or work with elderly or children (e.g. daycare provider, senior citizen care giver).
- Subjects who have received immunosuppressive treatment within the last 12 months
- BMI is greater than 35
- History of symptoms consistent with a viral URI within the past 21 days
- Family history or medical history of liver disease or bleeding disorders
- Have not received systemic corticosteroids for 3 months prior to Screening
- Have an ACT score >19 at the time of enrollment.
- Antiplatelet agents other than aspirin
- Subjects who have a positive COVID-19 test will be excluded for 8 weeks
Sites / Locations
- University of Texas Medical BranchRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Active Comparator
Arm Label
Healthy
Allergic Rhinitis
Allergic Ashthma
Arm Description
Subjects without asthma, COPD, rhinitis and with negative allergen test
Subjects without asthma, COPD and with positive allergen test
Subjects with asthma and positive allergen test
Outcomes
Primary Outcome Measures
ZEB-1 Expression
Q-PCR
Type III Interferon
Q-RT-PCR
PD-L1 Expression
Q-RT-PCR
RV16 Viral Titer
Plaque Assays
Secondary Outcome Measures
CD8 T cells in bronchoalveolar lavage fluid
Proportion and number of CD8+ T cells
Airway Remodeling
Lamina reticularis thickness
URI Cold Symptoms
WURSS21 Questionnaire
Full Information
NCT ID
NCT05331170
First Posted
April 8, 2022
Last Updated
May 5, 2023
Sponsor
The University of Texas Medical Branch, Galveston
1. Study Identification
Unique Protocol Identification Number
NCT05331170
Brief Title
Viral Mucosal Reprogramming
Acronym
VMR
Official Title
Epigenetic Mechanism Reprogramming Mucosal Anti-viral Immunity in Allergic Asthma VIRAL MUCOSAL REPROGRAMMING
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 27, 2023 (Actual)
Primary Completion Date
May 1, 2027 (Anticipated)
Study Completion Date
May 1, 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The University of Texas Medical Branch, Galveston
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a mechanistic, controlled, open-label, single-site study to evaluate the effects of RG-RV16 inoculation on airway mucosal gene expression and airway remodeling in 25 healthy controls (HC), in 25 allergic rhinitis subjects (AR) with cat dander allergy, and in 25 allergic asthmatic subjects (AA) with cat dander allergy. Three groups (HC, AR, and AA) will undergo screening to establish clinical history, will undergo pulmonary function testing (spirometry), and will have blood drawn for clinical characterization (IgE, , ImmunoCAP, CBC and differential), and for assessing the presence of existing neutralizing antibody against RV16. Only those who meet criteria will be permitted to continue into the interventional and run-out phases of the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma, Allergic Rhinitis, Cat Allergy, Healthy
Keywords
Asthma, Allergy, Allergic, Rhinitis, Airway, Cat dander, Respiratory
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
75 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Healthy
Arm Type
Active Comparator
Arm Description
Subjects without asthma, COPD, rhinitis and with negative allergen test
Arm Title
Allergic Rhinitis
Arm Type
Active Comparator
Arm Description
Subjects without asthma, COPD and with positive allergen test
Arm Title
Allergic Ashthma
Arm Type
Active Comparator
Arm Description
Subjects with asthma and positive allergen test
Intervention Type
Biological
Intervention Name(s)
Research Grade RG-RV
Intervention Description
Exploration of the effects of RV inoculation on human airway mucosal programming in vivo
Primary Outcome Measure Information:
Title
ZEB-1 Expression
Description
Q-PCR
Time Frame
Immediate
Title
Type III Interferon
Description
Q-RT-PCR
Time Frame
Immediate
Title
PD-L1 Expression
Description
Q-RT-PCR
Time Frame
Immediate
Title
RV16 Viral Titer
Description
Plaque Assays
Time Frame
48 hours after inoculation
Secondary Outcome Measure Information:
Title
CD8 T cells in bronchoalveolar lavage fluid
Description
Proportion and number of CD8+ T cells
Time Frame
Immediate and 48hrs post RV16 inoculation
Title
Airway Remodeling
Description
Lamina reticularis thickness
Time Frame
Immediate and 48 hrs post RV16 inoculation
Title
URI Cold Symptoms
Description
WURSS21 Questionnaire
Time Frame
Immediate and up to 7 days following inoculation
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Healthy Normal Control Group
Subject must be able to understand and provide informed consent
Age: 18-60 inclusive
Sex: M or F
No history of asthma, COPD, rhinitis, or other clinically important respiratory disease
Non-smoker, or ex-smoker with <10 pack years, at least 5 years remote.
No history of diabetes or cardiovascular disease
Negative ImmunoCAP test to regionally relevant allergen panel obtained at Screening. Alternatively, documented history of a negative skin test or negative specific IgE obtained within the past 12 months.
Allergic Rhinitis Group
Subject must be able to understand and provide informed consent
Age: 18-60 inclusive
Sex: M or F
No history of asthma, COPD, or other clinically important respiratory disease
Non-smoker, or ex-smoker with <10 pack years, at least 5 years remote
No history of diabetes or cardiovascular disease
History of rhinitis, physician diagnosed, plus one of the following criteria within the past 12 months
Seasonal or perennial nasal congestion or sneezing
Seasonal or perennial conjunctival infection or watering
No evidence of airway obstruction (FEV1:FVC ≥ lower limit of normal)
Positive ImmunoCAP test to cat. Documented history at any time of a positive skin test or a specific IgE measure at least Level 2 reactivity will meet this criterion. Subjects must have cat in home, have regular exposure to cat dander, or live in a home where a cat has lived within the past 6 months.
Allergic Asthma Group
Inclusion Criteria
Subject must be able to understand and provide informed consent
Age: 18-60 inclusive
Sex: M or F
No history of COPD or other clinically important respiratory disease other than asthma
Non-smoker, or ex-smoker with <10 pack years, at least 5 years remote
No history of diabetes or cardiovascular disease
History of mild-moderate asthma, physician diagnosed, plus one of the following criteria within the past 12 months
Airway obstruction (FEV1: FVC <0.6) that is significantly (at least 12% change from baseline, ATS criteria) reversible after 4 puffs of albuterol (obtained at Screening Visit or documented historical testing performed with the past 12 months)
Requiring ICS for control of asthma for at least 30 days within the past 12 months
Positive ImmunoCAP test to cat dander. Documented history at any time of a positive skin test or a specific IgE measure at least Level 2 reactivity will meet this criteria. Subjects must have cat in home, have regular exposure to cat dander, or live in a home where a cat has lived within the past 6 months.
Results of the CBC do not show clinically important abnormalities
Exclusion Criteria:
Healthy Group Normal Group
Inability or unwillingness of a participant to comply with study protocol
Currently taking inhaled corticosteroids, leukotriene modifier, or antihistamines for respiratory disease.
Neutralizing Ab to RV16 greater than or equal to 1:8
Pregnant or breastfeeding women or a woman who has a planned pregnancy during the course of the study. Menstruating females must have a negative pregnancy test at the screening visit. Pregnancy testing may be conducted prior to procedures as well at various times in the study.
Subjects with household or close contacts who are pregnant or planning a pregnancy during the main subject's participation, who have chronic respiratory disease, who are children under the age of 2 years, or who are adults over 60 years of age or are Immunosuppressed e.g. post-chemotherapy, HIV).
Subjects who provide healthcare services or work with elderly or children (e.g. daycare provider, senior citizen care giver).
Allergic Rhinitis Group
Inability or unwillingness of a participant to comply with study protocol
Currently using inhaled steroids, or oral montelukast for respiratory disease
Neutralizing Ab to RV16 greater than or equal to 1:8
Pregnant or breastfeeding women or a woman who has a planned pregnancy during the course of the study. Menstruating females must have a negative pregnancy test at screening visit. Pregnancy testing may be conducted prior to procedures as well at various times in the study.
Subjects with household or close contacts who are pregnant or planning a pregnancy during the main subject's participation, who have chronic respiratory disease, who are children under the age of 2 years, or who are adults over 60 years of age or are Immunosuppressed e.g. post-chemotherapy, HIV) .
Subjects who provide healthcare services or work with elderly or children (e.g. daycare provider, senior citizen care giver).
Subjects who have received immunosuppressive treatment within the last 12 months
BMI is greater than 35
History of symptoms consistent with a viral URI within the past 21 days
Results of the CBC do not show clinically important abnormalities
Family history or medical history of liver disease or bleeding disorders
Have not received systemic corticosteroids for 3months prior to Screening
Antiplatelet agents other than aspirin
Subjects who have a positive COVID-19 test will be excluded for 8 weeks
Allergic Asthma Group
Inability or unwillingness of a participant to comply with study protocol
Currently taking medications for respiratory diseases other than ICS, montelukast, or rescue albuterol or LABAs.
Neutralizing Ab to RV16 greater than or equal to 1:8
FEV1: FVC ratio less than 0.6, or FEV1 less than 60% predicted
Recent (<30 days) exacerbation of asthma requiring systemic corticosteroids
ICS greater than fluticasone 500 mcg/day or its equivalent (GINA 2019 table) at screening.
Pregnant or breastfeeding women or a woman who has a planned pregnancy during the course of the study. Menstruating females must have a negative pregnancy test at screening. Pregnancy testing may be conducted prior to procedures as well at various times in the study.
Subjects with household or close contacts who are pregnant or planning a pregnancy during the main subject's participation, who have chronic respiratory disease, who are children under the age of 2 years, or who are adults over 60 years of age or are Immunosuppressed e.g. post-chemotherapy, HIV) .
Subjects who provide healthcare services or work with elderly or children (e.g. daycare provider, senior citizen care giver).
Subjects who have received immunosuppressive treatment within the last 12 months
BMI is greater than 35
History of symptoms consistent with a viral URI within the past 21 days
Family history or medical history of liver disease or bleeding disorders
Have not received systemic corticosteroids for 3 months prior to Screening
Have an ACT score >19 at the time of enrollment.
Antiplatelet agents other than aspirin
Subjects who have a positive COVID-19 test will be excluded for 8 weeks
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lisa Sweeney, RN
Phone
409-747-5871
Email
lanemeth@utmb.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
William J. Calhoun, MD
Organizational Affiliation
University of Texas
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Texas Medical Branch
City
Galveston
State/Province
Texas
ZIP/Postal Code
77555
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lisa Sweeney, RN
Phone
409-747-5871
Email
lanemeth@utmb.edu
First Name & Middle Initial & Last Name & Degree
Cindy Mitchell, CCRC
Phone
409-772-5508
Email
cimitche@utmb.edu
First Name & Middle Initial & Last Name & Degree
William J. Calhoun, M.D
12. IPD Sharing Statement
Learn more about this trial
Viral Mucosal Reprogramming
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