Endothelial Dysfunction in Post-infection Fatigue Syndromes

Long COVID Clinical Trial

Official title:

Endothelial Dysfunction in Post-infection Fatigue Syndromes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06463106
• Other study ID #: FWF_KLP9628023
• Status: Completed
• Start date: June 1, 2021
• Est. completion date: December 1, 2022

Study information

• Verified date: June 2024
• Source: FH Joanneum Gesellschaft mbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 107
• Est. completion date: December 1, 2022
• Est. primary completion date: November 30, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Fatigue Syndrome
• Fatigue
• Fatigue Syndrome, Chronic
• Long COVID
• Syndrome

Locations

Country	Name	City	State
Austria	FH JOANNEUM University of Applied Sciences	Graz

Sponsors (1)

Lead Sponsor	Collaborator
FH Joanneum Gesellschaft mbH

Country where clinical trial is conducted

Austria, 

References & Publications (3)

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. — View 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. Erratum In: Sci Rep. 2021 Aug 6;11(1):16386. doi: 10.1038/s41598-021-95087-3. — View 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 May 10. doi: 10.1007/s40618-024-02334-1. Online ahead of print. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Circulating levels of L-arginine metabolites	Ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS)	6 months
Primary	Markers of endothelial inflammation	ELISA	6 months
Primary	Production of reactive oxygen species (ROS) in endothelial cells	Fluorometric assay	6 months
Primary	Endothelial permeability	3D culture model	6 months
Primary	Angiogenesis	3D culture model	6 months
Primary	Epigenetic and transcriptomic patterns in endothelial cells	Genome wide DNA methylation and RNA sequencing (RNA-seq)	6 months

External Links

•   FWF / Austrian Science Fund