Usage of Spirometry in Managing IgG Therapy in CVID With Airway Disease
Primary Purpose
Common Variable Immunodeficiency
Status
Not yet recruiting
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Hizentra
Sponsored by
About this trial
This is an interventional treatment trial for Common Variable Immunodeficiency
Eligibility Criteria
Inclusion Criteria:
- Patients who meet criteria for common variable immune deficiency (CVID) who are on stable IGRT for at least 3 months and who have an FEF25-75% between 50% and 80% of predicted.
- Patients who are already on Hizentra will be preferred.
Exclusion Criteria:
- Age <21 or cannot perform spirometry.
- Smokers with 20 pack years or more, and active smokers will not be included among the study subjects, but will be considered separately as an ancillary study.
- Patients with specific antigen-specific antibody deficiencies or X-linked agammaglobulinemia on IGRT will not be included among the 20 study subjects, but will be considered separately in ancillary studies.
- Patients with heart failure, TB, bronchiolitis, or lymphangioleiomyomatosis.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
No Intervention
Experimental
Arm Label
Control Group
Treatment Group
Arm Description
11 subjects will be treated for 6 months at their current dose of Hizentra
11 subjects will have their level of IGRT increased by the equivalent of 0.05 gm/kg in dose per 4 weeks, adjusted for bioavailability as per manufacturer's instructions. On average, rounded up to the nearest gram, this will typically increase their dose of Hizentra by 2 gm per week.
Outcomes
Primary Outcome Measures
FEV1 at baseline
Pulmonary function will be measured by forced expiratory volume in one second (FEV1) at baseline.
FEV1 at 3 months
Pulmonary function will be measured by forced expiratory volume in one second (FEV1) at three months into the study.
FEV1 at 6 months.
Pulmonary function will be measured by forced expiratory volume in one second (FEV1) at six months into the study.
FVC at baseline
Pulmonary function will be measured by forced vital capacity (FVC) at baseline.
FVC at 3 months
Pulmonary function will be measured by forced vital capacity (FVC) at three months.
FVC at 6 months.
Pulmonary function will be measured by forced vital capacity (FVC) at six months.
FEF25-75% at baseline
Pulmonary function will be measured by forced expiratory flow at 25 and 75% of the pulmonary volume (FEF25-75%) at baseline.
FEF25-75% at 3 months
Pulmonary function will be measured by forced expiratory flow at 25 and 75% of the pulmonary volume (FEF25-75%) at 3 months.
FEF25-75% at 6 months
Pulmonary function will be measured by forced expiratory flow at 25 and 75% of the pulmonary volume (FEF25-75%) at six months.
FEV1/FVC ratio at baseline
FEV1/FVC ratio will be calculated at baseline. The FEV1/FVC ratio is the ratio of the forced expiratory volume in the first one second (FEV1) to the forced vital capacity (FVC) of the lungs.
FEV1/FVC ratio at 3 months
FEV1/FVC ratio will be calculated at 3 months. The FEV1/FVC ratio is the ratio of the forced expiratory volume in the first one second (FEV1) to the forced vital capacity (FVC) of the lungs.
FEV1/FVC ratio at 6 months
FEV1/FVC ratio will be calculated at 6 months. The FEV1/FVC ratio is the ratio of the forced expiratory volume in the first one second (FEV1) to the forced vital capacity (FVC) of the lungs.
FOT at baseline.
Forced Oscillation Technique (FOT) will be measured at baseline. Forced Oscillation Technique (FOT) measures lung impedance during tidal breathing.
FOT at 3 months.
Forced Oscillation Technique (FOT) will be measured at 3 months. Forced Oscillation Technique (FOT) measures lung impedance during tidal breathing.
FOT at 6 months.
Forced Oscillation Technique (FOT) will be measured at 6 months. Forced Oscillation Technique (FOT) measures lung impedance during tidal breathing.
Secondary Outcome Measures
FACIT score at baseline and monthly on therapy
assess the effect of increasing the dose of IGRT on the patients' well-being by quantitating their fatigue level. Scores range from zero (no fatigue) to 52 (maximum fatigue/worse outcome).
PADQOL-16 at baseline and monthly on therapy
assess the effect of increasing the dose of IGRT on the patients' well-being by quantitating their quality of life. Scores range from zero (no impairment) to 32 (maximum impairment/worse outcome).
St. George's Respiratory Questionnaire at baseline and monthly on therapy
Disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. Scores range from zero (no impairment) to 100 (maximum impairment/worse outcome).
Full Information
NCT ID
NCT05193552
First Posted
August 6, 2021
Last Updated
September 27, 2023
Sponsor
University of Alabama at Birmingham
1. Study Identification
Unique Protocol Identification Number
NCT05193552
Brief Title
Usage of Spirometry in Managing IgG Therapy in CVID With Airway Disease
Official Title
A Prospective Study of the Utility of Spirometry to Identify and Manage Immunoglobulin Replacement Dosage in Primary Antibody Deficiency in Patients With Potentially Reversible Airway Disease
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
February 15, 2024 (Anticipated)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
December 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Alabama at Birmingham
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Although there is evidence in the literature that gammaglobulin replacement therapy can lead to a reduction in the prevalence of pulmonary infection and improved lung function, there is no published study to guide immunologists regarding the use of spirometry in titrating IG therapy to assist in the management of immunodeficiency patients with regards to gammaglobulin replacement therapy.
The investigators propose to study the use of spirometry to identify patients that could potentially benefit from an increase in IGRT. The investigators will identify 22 common variable immune deficiency (CVID) study subjects on stable IGRT replacement therapy equivalent to 0.40 to 0.60 gm/kg per 4 weeks who have evidence of mild to moderate obstruction as assessed by an FEF25-75% between 50% and 80% of predicted. Patients who are on Hizentra will be preferentially recruited. Of these 22, 11 will be identified at random and treated for 6 months at their current dose (control population). The remaining 11 study subjects (treatment group) will have their level of IGRT increased by the equivalent of 0.05 gm/kg in dose per 4 weeks, adjusted for bioavailability as per manufacturer's instructions. On average, rounded up to the nearest gram, this will typically increase their dose of Hizentra by 2 gm per week.
Detailed Description
The key finding of the published retrospective study was that common variable immune deficiency (CVID) patients with moderate, presumed reversible, obstruction on stable, therapeutic doses of IgG who exhibited a decline in lung function from one clinic visit to the next responded to an increased dose of IgG with an improvement in lung function as assessed by spirometry.
The investigators now wish perform a clinical trial to assess whether primary antibody deficiency patients receiving IGRT who fit in this range of obstruction, i.e. an FEF25-75% that is 50-80% of predicted, will demonstrate an increase in lung function, as assessed by spirometry, after increasing the dose of IGRT. The presumption is that obstruction at this level is most likely due to the effects of subclinical infections that can be reduced or avoided by increasing the amount of gammaglobulin received by the patients.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Common Variable Immunodeficiency
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
22 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Control Group
Arm Type
No Intervention
Arm Description
11 subjects will be treated for 6 months at their current dose of Hizentra
Arm Title
Treatment Group
Arm Type
Experimental
Arm Description
11 subjects will have their level of IGRT increased by the equivalent of 0.05 gm/kg in dose per 4 weeks, adjusted for bioavailability as per manufacturer's instructions. On average, rounded up to the nearest gram, this will typically increase their dose of Hizentra by 2 gm per week.
Intervention Type
Drug
Intervention Name(s)
Hizentra
Other Intervention Name(s)
SQ gammaglobulin therapy
Intervention Description
subjects level of IGRT will be adjusted for bioavailability as per manufacturer's instructions
Primary Outcome Measure Information:
Title
FEV1 at baseline
Description
Pulmonary function will be measured by forced expiratory volume in one second (FEV1) at baseline.
Time Frame
baseline
Title
FEV1 at 3 months
Description
Pulmonary function will be measured by forced expiratory volume in one second (FEV1) at three months into the study.
Time Frame
3 months
Title
FEV1 at 6 months.
Description
Pulmonary function will be measured by forced expiratory volume in one second (FEV1) at six months into the study.
Time Frame
6 months
Title
FVC at baseline
Description
Pulmonary function will be measured by forced vital capacity (FVC) at baseline.
Time Frame
baseline
Title
FVC at 3 months
Description
Pulmonary function will be measured by forced vital capacity (FVC) at three months.
Time Frame
3 months
Title
FVC at 6 months.
Description
Pulmonary function will be measured by forced vital capacity (FVC) at six months.
Time Frame
6 months
Title
FEF25-75% at baseline
Description
Pulmonary function will be measured by forced expiratory flow at 25 and 75% of the pulmonary volume (FEF25-75%) at baseline.
Time Frame
baseline
Title
FEF25-75% at 3 months
Description
Pulmonary function will be measured by forced expiratory flow at 25 and 75% of the pulmonary volume (FEF25-75%) at 3 months.
Time Frame
3 months
Title
FEF25-75% at 6 months
Description
Pulmonary function will be measured by forced expiratory flow at 25 and 75% of the pulmonary volume (FEF25-75%) at six months.
Time Frame
6 months
Title
FEV1/FVC ratio at baseline
Description
FEV1/FVC ratio will be calculated at baseline. The FEV1/FVC ratio is the ratio of the forced expiratory volume in the first one second (FEV1) to the forced vital capacity (FVC) of the lungs.
Time Frame
baseline
Title
FEV1/FVC ratio at 3 months
Description
FEV1/FVC ratio will be calculated at 3 months. The FEV1/FVC ratio is the ratio of the forced expiratory volume in the first one second (FEV1) to the forced vital capacity (FVC) of the lungs.
Time Frame
3 months
Title
FEV1/FVC ratio at 6 months
Description
FEV1/FVC ratio will be calculated at 6 months. The FEV1/FVC ratio is the ratio of the forced expiratory volume in the first one second (FEV1) to the forced vital capacity (FVC) of the lungs.
Time Frame
6 months
Title
FOT at baseline.
Description
Forced Oscillation Technique (FOT) will be measured at baseline. Forced Oscillation Technique (FOT) measures lung impedance during tidal breathing.
Time Frame
baseline
Title
FOT at 3 months.
Description
Forced Oscillation Technique (FOT) will be measured at 3 months. Forced Oscillation Technique (FOT) measures lung impedance during tidal breathing.
Time Frame
3 months
Title
FOT at 6 months.
Description
Forced Oscillation Technique (FOT) will be measured at 6 months. Forced Oscillation Technique (FOT) measures lung impedance during tidal breathing.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
FACIT score at baseline and monthly on therapy
Description
assess the effect of increasing the dose of IGRT on the patients' well-being by quantitating their fatigue level. Scores range from zero (no fatigue) to 52 (maximum fatigue/worse outcome).
Time Frame
6 months
Title
PADQOL-16 at baseline and monthly on therapy
Description
assess the effect of increasing the dose of IGRT on the patients' well-being by quantitating their quality of life. Scores range from zero (no impairment) to 32 (maximum impairment/worse outcome).
Time Frame
6 months
Title
St. George's Respiratory Questionnaire at baseline and monthly on therapy
Description
Disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. Scores range from zero (no impairment) to 100 (maximum impairment/worse outcome).
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Patients who meet criteria for common variable immune deficiency (CVID) who are on stable IGRT for at least 3 months and who have an FEF25-75% between 50% and 80% of predicted.
Patients who are already on Hizentra will be preferred.
Exclusion Criteria:
Age <21 or cannot perform spirometry.
Smokers with 20 pack years or more, and active smokers will not be included among the study subjects, but will be considered separately as an ancillary study.
Patients with specific antigen-specific antibody deficiencies or X-linked agammaglobulinemia on IGRT will not be included among the 20 study subjects, but will be considered separately in ancillary studies.
Patients with heart failure, TB, bronchiolitis, or lymphangioleiomyomatosis.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Leigh Powell
Phone
2053319159
Email
lcpowell@uabmc.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Tracy Hwangpo, MD/PhD
Phone
2059960161
Email
thwangpo@uabmc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Harry Schroeder, MD/PhD
Organizational Affiliation
University of Alabama at Birmingham
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
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Usage of Spirometry in Managing IgG Therapy in CVID With Airway Disease
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