Plasma exchange with albumin replacement and disease progression in amyotrophic lateral sclerosis: a pilot study

Abstract

Background: Plasma exchange (PE) is used to treat a range of neurological disorders. Based on results demonstrated in Alzheimer's disease, we theorized that PE with albumin replacement (PE-A) might alter the metabolic profile of plasma and cerebrospinal fluid in patients with amyotrophic lateral sclerosis (ALS) by removing disease-inducing molecules. The aim of this study was to evaluate the effect of PE-A on disease progression in ALS.

Methods: In this open-label, non-controlled, single-arm, prospective pilot study, 13 adults with ALS had 6 months' treatment with PE-A 5% and 6 months' follow-up. Primary endpoints were changes from baseline in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score and forced vital capacity (FVC) through 48 weeks. A post hoc analysis compared individual patient data with the expected ALSFRS-R progression slope.

Results: The median ALSFRS-R score declined throughout the study, although the rate of decline was slower than expected in seven patients at treatment end and in five patients at study end. Six patients remained in the same baseline slope progression category, and four patients improved their slope category at treatment end. Median FVC decreased significantly during the study. Treatment was well tolerated. Of 330 PE-A procedures, 0.9% were associated with potentially related adverse events.

Conclusion: Although functional impairment progressed, about two-thirds of patients showed a slower than expected rate of decline at treatment end. Most patients had unaltered (54.5%) or reduced (36.4%) ALSFRS-R slope progression at treatment end. Further evaluation of PE-A in controlled studies involving more patients is warranted.

Eudract number: 2013-004842-40.

Trial registration: ClinicalTrials.gov identifier: NCT02479802.

Keywords: Albumin; Amyotrophic lateral sclerosis; Cognitive function; Motor dysfunction; Plasma exchange.

Conflict of interest statement

Mónica Povedano, Andrés Paipa, Raúl Domínguez and Sandra Ortega report no conflicts of interest. Miquel Barceló, Michael K. Woodward, Maria Esperança Aragonés, Raquel Horrillo, Montserrat Costa and Antonio Páez are employees of Grifols, the manufacturer of Albutein®.

© 2021. The Author(s).

Figures

Fig. 1

Patient disposition

Fig. 2

Progression of disability: Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) overall score by week in evaluable patients (n = 13). Treatment ended week 24 (assessment performed at week 25) and follow-up ended week 48. Box plot displays median (IQR). Whiskers ( −) are the minimum value; whiskers ( +) are the maximum value. The mean value is indicated by a plus sign. Green dots are slow progressor patients with an ALSFRS-R slope less than − 0.8 points/month. Orange dots are normal progressor patients with an ALSFRS-R slope between − 0.8 and − 1.33 points per month. Red dots are fast progressor patients with an ALSFRS-R slope greater than − 1.33 points/month. IQR, interquartile range

Fig. 3

Electromyography motor nerve conduction study results for amplitude (mV) at baseline, treatment end (assessment performed week 25) and end of follow-up in evaluable patients

Fig. 4

Albumin fatty acid binding capacity and lipid peroxidation by week in evaluable patients (n = 13). Treatment ended at week 24 (assessment performed at week 24) and follow-up ended at week 48. 8-isoPGF2α, 8-iso-prostaglandinF2α; Kd, dissociation constant; MS, mass spectrometry; PE, plasma exchange