Venous Bicarbonate as a Prognostic Biomarker and Proposed Proxy for Vital Capacity to Be Used as an Eligibility Criterion in Amyotrophic Lateral Sclerosis Clinical Trials.

Background: Clinical trials for people living with ALS (pALS) all list vital capacity (VC) as an important eligibility criterion. However, VC measures are challenging to perform among pALS, especially bulbar pALS. Additionally, since the disease rapidly changes, the VC can change in a short duration of time, making it unreliable.

Objective: We aimed to investigate the association of venous bicarbonate with VC as an alternative criterion for trial eligibility. We also wanted to examine whether venous bicarbonate could be used as a prognostic biomarker for survival in ALS.

Methods: We included pALS from the Swedish ALS/MND Registry between January 1, 2019 and July 31, 2022. pALS had to have serum bicarbonate values and ALSFRS-R available close to diagnosis. Spearman correlations, Kaplan-Meier curves, and Cox proportional hazard regressions were used to assess the associations of venous bicarbonate with VC, other clinical characteristics, and survival.

Results: Among the 117 pALS included in the study, we observed a negative correlation between venous bicarbonate and VC among spinal and bulbar pALS (ρ = -0.346, p = 0.002 and ρ = -0.367, p = 0.024, respectively). Venous bicarbonate negatively correlated with ALSFRS-R (ρ = -0.377, p < 0.001), specifically among bulbar pALS (ρ = -0.595, p < 0.001), but positively correlated with KING's stage (ρ = 0.248, p = 0.007). High level of venous bicarbonate appeared to be associated with shorter survival.

Conclusions: Venous bicarbonate appears to be a prognostic biomarker for survival among pALS. This cheap and easily accessible measure could potentially be an alternative for VC as an eligibility criterion in ALS trials.