Usage of Spirometry in Managing IgG Therapy in CVID With Airway Disease

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Common Variable Immunodeficiency

Intervention / Treatment
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* Drug: Hizentra


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control Group<br>11 subjects will be treated for 6 months at their current dose of Hizentra | |
| Experimental: Treatment Group<br>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. | Drug: Hizentra<br>* subjects level of IGRT will be adjusted for bioavailability as per manufacturer's instructions<br>* Other names: SQ gammaglobulin therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FEV1 at baseline | Pulmonary function will be measured by forced expiratory volume in one second (FEV1) at baseline. | baseline | 
| FEV1 at 3 months | Pulmonary function will be measured by forced expiratory volume in one second (FEV1) at three months into the study. | 3 months | 
| FEV1 at 6 months. | Pulmonary function will be measured by forced expiratory volume in one second (FEV1) at six months into the study. | 6 months | 
| FVC at baseline | Pulmonary function will be measured by forced vital capacity (FVC) at baseline. | baseline | 
| FVC at 3 months | Pulmonary function will be measured by forced vital capacity (FVC) at three months. | 3 months | 
| FVC at 6 months. | Pulmonary function will be measured by forced vital capacity (FVC) at six months. | 6 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. | 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. | 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. | 6 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. | baseline | 
| 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. | 3 months | 
| 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. | 6 months | 
| FOT at baseline. | Forced Oscillation Technique (FOT) will be measured at baseline. Forced Oscillation Technique (FOT) measures lung impedance during tidal breathing. | baseline | 
| FOT at 3 months. | Forced Oscillation Technique (FOT) will be measured at 3 months. Forced Oscillation Technique (FOT) measures lung impedance during tidal breathing. | 3 months | 
| FOT at 6 months. | Forced Oscillation Technique (FOT) will be measured at 6 months. Forced Oscillation Technique (FOT) measures lung impedance during tidal breathing. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 6 months | 
| 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). | 6 months | 
| 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). | 6 months |