Potential treatment of long COVID fatigue revealed in new Trial

The researchers from the University of Oxford revealed that participants given the treatment reported feeling less tired than those given a placebo. The investigational therapy, AXA1125, was developed by US pharmaceutical company Axcella Therapeutics.

"Compared to the placebo, AXA1125 did not improve the study's primary endpoint (τPCr-measure of mitochondrial respiration); however, it significantly improved fatigue-based symptoms in patients with Long COVID after a treatment period of four weeks," the study stated.

According to the authors, the study is one of the first randomized, double-blind, placebo-controlled trials of a potential long COVID treatment. RCTs are considered the gold standard for examing possible treatments for an illness. The study was double-blind; neither the patients nor the investigators working with the patients knew which patients had the treatment and which patients had a placebo.

'Long COVID' is the persistent symptoms, commonly fatigue, following SARS-CoV-2 infection that lasts beyond 12 weeks. Potential causes include reduced cellular bioenergetics and mitochondrial function. Previously, AXA1125 was shown to improve bioenergetics and increase β-oxidation along with other certain clinical conditions, and therefore it was suggested to reduce fatigue tied to Long COVID.

Against the above background, Lucy E.M. Finnigan, University of Oxford, John Radcliffe Hospital, Oxford, UK, and colleagues aimed to assess the safety, efficacy and tolerability of AXA1125 in Long COVID.

The study involved 41 patients; half had the investigational treatment, a twice-daily intake of an orange-flavoured powder dissolved in water for four weeks, whereas the other half had a placebo. All the participants completed the study, and none showed severe adverse effects of either the treatment or the placebo. On average, patients had fatigue symptoms for about 18 months before entering the study.

The researchers also tracked mitochondrial health in the patients' muscles before and after their medication intake. For this purpose, they used state-of-the-art magnetic resonance spectroscopy scans of the calf muscles as the patients bent and straightened their legs against the mild resistance from an exercise band.

The study revealed the following findings:

• There was no significant difference in the changes in skeletal muscle phosphocreatine recovery time constant (τPCr) and 6-min walk test (6MWT) between the treatment (n = 21) and placebo group (n = 20).
• Treatment with AXA1125 was linked with significantly reduced day 28 Chalder Fatigue Questionnaire [CFQ-11] fatigue score compared to placebo.
• Eleven (52.4%, AXA1125) and four (20.0%, placebo) patients reported treatment-emergent adverse events; none were serious or led to treatment discontinuation.

"Our findings focus specifically on fatigue, rather than the cardiovascular and breathlessness issues that other long COVID patients have reported," Principal Investigator, Associate Professor Betty Raman from the Radcliffe Department of Medicine at Oxford University, said in a press release.

"We also selected patients having clear signs of disturbed mitochondrial function – effects of the medication on other symptoms remain to be evaluated in future studies."

Reference:

The study, "Efficacy and tolerability of an endogenous metabolic modulator (AXA1125) in fatigue-predominant long COVID: a single-centre, double-blind, randomized controlled phase 2a pilot study," was published in The Lancet.

DOI: https://doi.org/10.1016/j.eclinm.2023.101946