Standardization of the single-breath diffusing capacity in a multicenter clinical trial

Area of Science:

• Pulmonary Medicine
• Clinical Trials
• Diabetes Research

Background:

• Multicenter trials face challenges in standardizing single-breath diffusing capacity of the lung for carbon monoxide (DLCO) measurements due to variability in equipment and training.
• Standardized DLCO measurement is crucial for safety assessments of new therapies like inhalable insulin.

Purpose of the Study:

• To assess the feasibility and reliability of a standardized methodology for single-breath DLCO measurements in a multicenter clinical trial setting.
• To ensure high-quality DLCO data collection for the safety assessment of inhaled human insulin in type 1 diabetes patients.

Main Methods:

• An open-label, 24-week, parallel-group study involving participants with type 1 diabetes receiving inhaled or subcutaneous insulin.
• Standardization involved uniform instrumentation, centrally trained coordinators, and centralized data monitoring with rapid feedback on test quality.
• Single-breath DLCO was monitored using the standardized methodology throughout the study.

Main Results:

• Over 11,000 DLCO efforts were completed across 33 sites by 226 participants.
• 75.2% and 95.5% of testing sessions yielded two acceptable DLCO efforts with variation < 1 and 2 mL/min/mm Hg, respectively.
• The root mean square intrasubject coefficient of variation in DLCO was 6.01% at the end of the study.

Conclusions:

• The implemented standardized methodology enables the collection of high-quality single-breath DLCO data in multicenter clinical trials.
• The reliability of the standardized DLCO measurements is comparable to that of spirometry.
• This approach facilitates precise safety assessments in trials involving new inhaled medications.