ABSTRACT
STUDY DESIGN: Double-blind, randomized, placebo-controlled, parallel-group multicentric phase IIA clinical trial. OBJECTIVE: To assess the safety and tolerability of oral administration of NFX-88 in subjects with chronic spinal cord injury (SCI) and explore its efficacy in pain control. SETTING: A total of 7 spinal cord injury rehabilitation units in Spain. METHODS: A total of 61 adult with traumatic complete or incomplete spinal cord injury (C4-T12 level), were randomised 1:1:1:1 to a placebo, NFX88 1.05 g, 2.1 g, 4.2 g/day for up to 12 weeks. The placebo or NFX-88 was administered as add-on therapy to pre-existing pregabalin (150-300 mg per day). Safety and tolerability were evaluated, and the Visual Analogue Scale (VAS) was the primary measure to explore the efficacy of NFX-88 in pain control. RESULTS: No severe treatment-related adverse effects were reported for any of the four study groups. 44 SCI individuals completed the study and were analysed. The data obtained from the VAS analysis and the PainDETECT Questionnaire (PD-Q) suggested that the combination of NFX88 with pregabalin is more effective than pregabalin with placebo at reducing neuropathic pain (NP) in individuals with SCI and that the dose 2.10 g/day causes the most dramatic pain relief. CONCLUSIONS: NFX88 treatment was found to be highly safe and well tolerated, with the dose of 2.10 g/day being the most effective at causing pain relief. Thus, the promising efficacy of this first-in-class lipid mediator deserves further consideration in future clinical trials.
ABSTRACT
The COVID-19 pandemic represents an unprecedented global challenge in this century. COVID-19 is a viral respiratory infection, yet the clinical characteristics of this infection differ in spinal cord injury patients from those observed in the general population. Cough and asthenia are the most frequent symptoms in this population. Moreover, infected spinal cord injury patients rarely present complications that require admission to an Intensive Care Unit, in contrast to the general population. Thus, there is a clear need to understand how COVID-19 affects spinal cord injury patients from a molecular perspective. Here, we employed an -omics strategy in order to identify variations in protein abundance in spinal cord injury patients with and without COVID-19. After a quantitative differential analysis using isobaric tags and mass spectrometry and a verification phase, we have found differences mainly related to coagulation and platelet activation. Our results suggest a key role of heparin in the response of spinal cord injury patients to COVID-19 infection, showing a significant correlation between these proteins and heparin dose. Although the number of patients is limited, these data may shed light on new therapeutic options to improve the management these patients and, possibly, those of the general population as well.
ABSTRACT
STUDY DESIGN: Cohort study of patients with spinal cord injury (SCI). OBJECTIVES: To describe the clinical and analytical features of a coronavirus disease 2019 (Covid-19) infected cohort with SCI to enable accurate diagnosis and to outline prevention measures. SETTING: This study was conducted at the National Hospital for Paraplegics (Toledo, Spain). METHODS: A cohort analysis of seven patients with SCI infected by Covid-19 was performed. Diagnosis was confirmed with reverse transcriptase polymerase chain reaction (RT-PCR) of nasal exudate or sputum samples. Clinical, analytical, and radiographic findings were registered. RESULTS: RT-PCR detected COVID-19 infection in all patients, affecting males and people with a cervical level of injury more often (five out of seven). The average delay for diagnostic confirmation was 4 days (interquartile range, 1-10). Fever was the most frequent symptom (six out of seven). The second most common symptom was asthenia (four out of seven), followed by dyspnea, cough, and expectoration (three out of seven for each symptom). The Modified Early Warning System score for Covid-19 severity rating was classified as severe in five out of seven cases. All but one patient showed radiological alterations evident in chest X-rays at the time of diagnosis. All patients recovered gradually. CONCLUSION: Our patients with SCI and Covid-19 infection exhibited fewer symptoms than the general population. Furthermore, they presented similar or greater clinical severity. The clinical evolution was not as pronounced as had been expected. This study recommends close supervision of the SCI population to detect early compatible signs and symptoms of Covid-19 infection.
