Clinical trial NCT06463106: Endothelial Dysfunction in Post-infection Fatigue Syndromes
Official title: Endothelial Dysfunction in Post-infection Fatigue Syndromes
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Chronic Fatigue Syndrome
Long COVID
Keywords: ME/CFS
Long COVID
Endothelial dysfunction
Lead sponsor: FH Joanneum Gesellschaft mbH
Sponsor class: INDUSTRY
First posted: 2024-06-17
Enrollment: 107
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: A sex/age-matched cohort (n=107) including (1) healthy controls and patients diagnosed with (2) ME/CFS and (3) Long-Covid according to the ethical approval granted by the Ethics Committee at the Medical University of Vienna (vote number: 2281/2020). Healthy individuals will be divided into two sub-groups: individuals without SARS-CoV-2 infection (HC1; n=30; females: 73.4%; age (years): 34.37 ± 12.30) and previously SARS-CoV-2 infected, fully convalescent patients (HC2; n=30; females: 73.4%; age (years): 34.10 ± 11.51).

Brief summary: Post-infection chronic fatigue syndromes, such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-COVID-19 condition (Long Covid), are conditions primarily characterized by debilitating fatigue. This fatigue can range from mild, where patients are still able to participate in some social activities (e.g., school, work), to moderate and severe, where sufferers are predominantly homebound and bedridden. As a result, ME/CFS and Long Covid not only negatively impact the quality of life of affected individuals and their caregivers but also represent a substantial and often silent burden on healthcare systems worldwide, including Austria. This is primarily because most cases remain undiagnosed due to the lack of standardized clinical assessments and diagnostic markers. Endothelial dysfunction, which is well known to affect blood flow, oxygen and nutrient delivery, and waste removal in the body, has been described as one of the key factors behind the symptoms experienced by ME/CFS and Long Covid patients. However, the mechanisms that might explain the development of endothelial dysfunction remain largely unexplored. Therefore, this project aims to evaluate key biological aspects related to the function of endothelial cells - a layer of cells lining blood vessels - using plasma samples from an Austrian cohort of ME/CFS and Long Covid patients. We expect that the findings from our study will provide new insights to better understand endothelial dysfunction in post-infection chronic fatigue syndromes, leading to improved patient stratification and tailored treatment alternatives.


Eligibility criteria: Inclusion Criteria:

The inclusion criteria for ME/CFS patients not infected with SARS-CoV-2 (n=17; females: 70.59%; age (years): 40.10 ± 10.80) and Long-Covid patients (n=30; females: 73.4%; age (years): 37.70 ± 9.96) include profound fatigue and at least one of the following symptoms: PEM, autonomic dysfunction, and/or orthostatic intolerance. All participants were included only if they were at least 12 weeks past an acute EBV infection and/or 10 weeks past an acute SARS-CoV-2 infection, respectively. SARS-CoV-2 specific IgA (A) and IgG (B) antibody titers were measured using commercial test kits (Anti-SARS-CoV-2-ELISA (IgA) and Anti-SARS-CoV-2-QuantiVac-ELISA (IgG); Euroimmun, Germany) in plasma samples.

Exclusion Criteria:

Participants' exclusion criteria included evidence of acute malignant diseases, diabetes mellitus, acute sepsis, chronic inflammatory gastrointestinal diseases, and frequent intake of analgesics, antacids, or antibiotics. Furthermore, no previously hospitalized SARS-CoV-2 patients were included, eliminating false-positive fatigue due to intensive care treatment, such as artificial respiration.

Primary outcomes:
measure: Circulating levels of L-arginine metabolites
timeFrame: 6 months
measure: Markers of endothelial inflammation
timeFrame: 6 months
measure: Production of reactive oxygen species (ROS) in endothelial cells
timeFrame: 6 months
measure: Endothelial permeability
timeFrame: 6 months
measure: Angiogenesis
timeFrame: 6 months
measure: Epigenetic and transcriptomic patterns in endothelial cells
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Graz
country: Austria
facility: FH JOANNEUM University of Applied Sciences
Study officials:
References:
citation: Pipper C, Bliem L, Leon LE, Mennickent D, Bodner C, Guzman-Gutierrez E, Stingl M, Untersmayr E, Wagner B, Bertinat R, Sepulveda N, Westermeier F. Sex and disease severity-based analysis of steroid hormones in ME/CFS. J Endocrinol Invest. 2024 Sep;47(9):2235-2248. doi: 10.1007/s40618-024-02334-1. Epub 2024 May 10.
citation: Bertinat R, Villalobos-Labra R, Hofmann L, Blauensteiner J, Sepulveda N, Westermeier F. Decreased NO production in endothelial cells exposed to plasma from ME/CFS patients. Vascul Pharmacol. 2022 Apr;143:106953. doi: 10.1016/j.vph.2022.106953. Epub 2022 Jan 21.
citation: Blauensteiner J, Bertinat R, Leon LE, Riederer M, Sepulveda N, Westermeier F. Altered endothelial dysfunction-related miRs in plasma from ME/CFS patients. Sci Rep. 2021 May 19;11(1):10604. doi: 10.1038/s41598-021-89834-9.