Clinical trial NCT05193552: 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
Overall status: RECRUITING
Phase: PHASE4
Conditions: Common Variable Immunodeficiency
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
First posted: 2022-01-18
Enrollment: 22
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. 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.
2. Patients who are already on Hizentra will be preferred.

Exclusion Criteria:

1. Age \<21 or cannot perform spirometry.
2. 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.
3. 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.
4. Patients with heart failure, TB, bronchiolitis, or lymphangioleiomyomatosis.

Primary outcomes:
measure: FEV1 at baseline
timeFrame: baseline
measure: FEV1 at 3 months
timeFrame: 3 months
measure: FEV1 at 6 months.
timeFrame: 6 months
measure: FVC at baseline
timeFrame: baseline
measure: FVC at 3 months
timeFrame: 3 months
measure: FVC at 6 months.
timeFrame: 6 months
measure: FEF25-75% at baseline
timeFrame: baseline
measure: FEF25-75% at 3 months
timeFrame: 3 months
measure: FEF25-75% at 6 months
timeFrame: 6 months
measure: FEV1/FVC ratio at baseline
timeFrame: baseline
measure: FEV1/FVC ratio at 3 months
timeFrame: 3 months
measure: FEV1/FVC ratio at 6 months
timeFrame: 6 months
measure: FOT at baseline.
timeFrame: baseline
measure: FOT at 3 months.
timeFrame: 3 months
measure: FOT at 6 months.
timeFrame: 6 months
Secondary outcomes:
measure: FACIT score at baseline and monthly on therapy
timeFrame: 6 months
measure: PADQOL-16 at baseline and monthly on therapy
timeFrame: 6 months
measure: St. George's Respiratory Questionnaire at baseline and monthly on therapy
timeFrame: 6 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Community Health 20
state: Alabama
Study officials:
affiliation: University of Alabama at Birmingham
name: Harry Schroeder, MD/PhD
role: PRINCIPAL_INVESTIGATOR
References: