Low-field Magnetic Resonance Imaging in Pediatric Post Covid-19

COVID-19 Clinical Trial

— FASCINATE  

Official title:

Low-field Magnetic Resonance Imaging to Assess Changes in Pulmonary Function Parameters in Confirmed Pediatric SARS-CoV-2 Infection

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05445531
• Other study ID #: 22-77-Bm
• Status: Recruiting
• Phase: N/A
• Start date: July 8, 2022
• Est. completion date: March 31, 2023

Study information

• Verified date: July 2022
• Source: University of Erlangen-Nürnberg Medical School
• Contact: Ferdinand Knieling, MD
• Phone: +49913185
• Email: ferdinand.knieling[@]uk-erlangen.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

SARS-CoV-2 (Severe acute respiratory syndrome coronavirus type 2) is a new coronavirus and identified causative agent of COVID-19 disease. These viruses predominantly cause mild colds, but can sometimes cause severe pneumonia and pulmonary skeletal changes. By low-field gastric magnetic resonance imaging (NF-MRI), only a small number of structural, scarring changes were seen in a preliminary study of pediatric and adolescent patients with past SARS-CoV-2 infection. In contrast, however, extensive changes in ventilation and blood flow function of the lungs were seen.

The long-term consequences and spontaneous progression of these changes on imaging are completely unclear. The aim of this study is to assess the course of these functional lung changes in pediatric and adolescent patients and to validate them with other standard clinical procedures.

Description:

SARS-CoV-2 (Severe acute respiratory syndrome coronavirus type 2) is a new coronavirus and identified causative agent of COVID-19 disease. They predominantly cause mild colds but can sometimes cause severe pneumonia and pulmonary skeletal disease. While the molecular basis for the changes in lung tissue or multi-organ involvement have been described, the age-specific long-term consequences, especially in children and adolescents, remain largely unexplained and misunderstood today.

Early publications from the primarily affected Chinese provinces described rather mild, partly asymptomatic courses in children. This is consistent with the observation that the risk of severe COVID-19 disease increases steeply from the age of 70 years, and is also determined by the severity of obesity as well as other risk factors. Developmental expression of tissue factors may be one reason for the relative protection of younger patients from severe courses of the disease.

However, it is now becoming increasingly clear that some individuals with milder initial symptoms of COVID-19 may suffer from variable and persistent symptoms for many months after initial infection - this includes children. A modern low-field MRI is located in Erlangen, Germany. This technique has already been used to demonstrate persistent damage to lung tissue in adult patients after COVID-19. The device with a field strength of 0.55 Tesla (T) currently has the world's largest aperture (and is thus particularly suitable for patients with claustrophobia, among other things), a very quiet operating noise, and lower energy absorption in the tissue due to the weaker magnetic field than MRI scanners with 1.5T or 3T. This allows MRI imaging in a very broad pediatric population without the need for sedation.

To date, no structural changes were revealed by means of this MRI technique - however, large defects in the area of ventilation and blood flow function of the lung are apparent in specific functional sequences. The aim of this study is to assess the course of these functional lung changes in pediatric and adolescent patients and to validate them with other standard clinical procedures.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 111
• Est. completion date: March 31, 2023
• Est. primary completion date: January 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years to 17 Years

Eligibility

Control arm:

Inclusion Criteria:

• Proof of SARS-CoV-2 infection and at least 2/3 times complete vaccination before infection (at least 14 days) (complete vaccination status according to German recommendations)

• Long Covid criteria not met according to AWMF S1 guideline

Exclusion Criteria:

• Acute SARS-CoV-2 infection and need for isolation

• Necessary quarantine

• Pregnancy, lactation

• Indication of acute infection

• Known pleural or pericardial effusion

• Critical condition (need for respiratory support, ventilation, oxygen administration, shock, symptomatic heart failure)

• Marked thoracic deformities

• Previous lung surgery

• Injuries that do not allow for physical stress testing

• Refusal of MRI imaging

• General contraindications to MRI examinations (e.g., electrical implants such as pacemakers or perfusion pumps, etc.)

• History, clinical, or other suspicion of pulmonary disease

• Current respiratory infection/symptomatology

• Pain leading to respiratory limitation

• Inhaled therapy (e.g., steroids or beta-mimetics)

• Immunosuppression

• Any condition that may lead to respiratory limitation (e.g., pain disorder)

• Obesity (>97% of age percentile)

Recovered arm:

Inclusion Criteria:

• Positive SARS-CoV-2 infection confirmed by PCR

• Long Covid criteria not met according to AWMF S1 guideline

Exclusion Criteria:

• Acute SARS-CoV-2 infection and need for isolation

• Necessary quarantine

• Pregnancy, lactation

• Indication of acute infection

• Known pleural or pericardial effusion

• Critical condition (need for respiratory support, ventilation, oxygen administration, shock, symptomatic heart failure)

• Marked thoracic deformities

• Previous lung surgery

• Injuries that do not allow for physical stress testing

• Refusal of MRI imaging

• General contraindications to MRI examinations (e.g., electrical implants such as pacemakers or perfusion pumps, etc.)

Long Covid arm:

Inclusion Criteria:

• Positive SARS-CoV-2 infection confirmed by PCR

• Long Covid criteria according to AWMF S1 guideline fulfilled

Exclusion Criteria:

• Acute SARS-CoV-2 infection and need for isolation

• Necessary quarantine

• Pregnancy, lactation

• Indication of acute infection

• Known pleural or pericardial effusion

• Critical condition (need for respiratory support, ventilation, oxygen administration, shock, symptomatic heart failure)

• Marked thoracic deformities

• Previous lung surgery

• Injuries that do not allow for physical stress testing

• Refusal of MRI imaging

• General contraindications to MRI examinations (e.g., electrical implants such as pacemakers or perfusion pumps, etc.)

Related Conditions & MeSH terms

• COVID-19
• Infections
• Long COVID
• Respiratory Tract Infections

Intervention

Diagnostic Test:
• Low-field magnetic resonance imaging
Functional and morphologic imaging of the lungs
• Nailfold capillaroscopy
Imaging of nailfold microvasculature
• Spiroergometry
Cardiopulmonary exercise testing
• Realtime deformability cytometry
High-throughput measurement of cell deformability and physical properties

Locations

Country	Name	City	State
Germany	University Hospital Erlangen	Erlangen	Bavaria

Sponsors (1)

Lead Sponsor	Collaborator
University of Erlangen-Nürnberg Medical School

Country where clinical trial is conducted

Germany, 

References & Publications (11)

Brodin P. Immune determinants of COVID-19 disease presentation and severity. Nat Med. 2021 Jan;27(1):28-33. doi: 10.1038/s41591-020-01202-8. Epub 2021 Jan 13. — View Citation

Duan YN, Zhu YQ, Tang LL, Qin J. CT features of novel coronavirus pneumonia (COVID-19) in children. Eur Radiol. 2020 Aug;30(8):4427-4433. doi: 10.1007/s00330-020-06860-3. Epub 2020 Apr 14. Review. — View Citation

Heiss R, Grodzki DM, Horger W, Uder M, Nagel AM, Bickelhaupt S. High-performance low field MRI enables visualization of persistent pulmonary damage after COVID-19. Magn Reson Imaging. 2021 Feb;76:49-51. doi: 10.1016/j.mri.2020.11.004. Epub 2020 Nov 18. — View Citation

Huang J, Hume AJ, Abo KM, Werder RB, Villacorta-Martin C, Alysandratos KD, Beermann ML, Simone-Roach C, Lindstrom-Vautrin J, Olejnik J, Suder EL, Bullitt E, Hinds A, Sharma A, Bosmann M, Wang R, Hawkins F, Burks EJ, Saeed M, Wilson AA, Mühlberger E, Kotton DN. SARS-CoV-2 Infection of Pluripotent Stem Cell-Derived Human Lung Alveolar Type 2 Cells Elicits a Rapid Epithelial-Intrinsic Inflammatory Response. Cell Stem Cell. 2020 Dec 3;27(6):962-973.e7. doi: 10.1016/j.stem.2020.09.013. Epub 2020 Sep 18. — View Citation

Karki R, Sharma BR, Tuladhar S, Williams EP, Zalduondo L, Samir P, Zheng M, Sundaram B, Banoth B, Malireddi RKS, Schreiner P, Neale G, Vogel P, Webby R, Jonsson CB, Kanneganti TD. Synergism of TNF-a and IFN-? Triggers Inflammatory Cell Death, Tissue Damage, and Mortality in SARS-CoV-2 Infection and Cytokine Shock Syndromes. Cell. 2021 Jan 7;184(1):149-168.e17. doi: 10.1016/j.cell.2020.11.025. Epub 2020 Nov 19. — View Citation

Lu X, Zhang L, Du H, Zhang J, Li YY, Qu J, Zhang W, Wang Y, Bao S, Li Y, Wu C, Liu H, Liu D, Shao J, Peng X, Yang Y, Liu Z, Xiang Y, Zhang F, Silva RM, Pinkerton KE, Shen K, Xiao H, Xu S, Wong GWK; Chinese Pediatric Novel Coronavirus Study Team. SARS-CoV-2 Infection in Children. N Engl J Med. 2020 Apr 23;382(17):1663-1665. doi: 10.1056/NEJMc2005073. Epub 2020 Mar 18. — View Citation

Sajuthi SP, DeFord P, Li Y, Jackson ND, Montgomery MT, Everman JL, Rios CL, Pruesse E, Nolin JD, Plender EG, Wechsler ME, Mak ACY, Eng C, Salazar S, Medina V, Wohlford EM, Huntsman S, Nickerson DA, Germer S, Zody MC, Abecasis G, Kang HM, Rice KM, Kumar R, Oh S, Rodriguez-Santana J, Burchard EG, Seibold MA. Type 2 and interferon inflammation regulate SARS-CoV-2 entry factor expression in the airway epithelium. Nat Commun. 2020 Oct 12;11(1):5139. doi: 10.1038/s41467-020-18781-2. — View Citation

Schuler BA, Habermann AC, Plosa EJ, Taylor CJ, Jetter C, Negretti NM, Kapp ME, Benjamin JT, Gulleman P, Nichols DS, Braunstein LZ, Hackett A, Koval M, Guttentag SH, Blackwell TS, Webber SA, Banovich NE; Vanderbilt COVID-19 Consortium Cohort; Human Cell Atlas Biological Network, Kropski JA, Sucre JM. Age-determined expression of priming protease TMPRSS2 and localization of SARS-CoV-2 in lung epithelium. J Clin Invest. 2021 Jan 4;131(1). pii: 140766. doi: 10.1172/JCI140766. — View Citation

Shelmerdine SC, Lovrenski J, Caro-Domínguez P, Toso S; Collaborators of the European Society of Paediatric Radiology Cardiothoracic Imaging Taskforce. Coronavirus disease 2019 (COVID-19) in children: a systematic review of imaging findings. Pediatr Radiol. 2020 Aug;50(9):1217-1230. doi: 10.1007/s00247-020-04726-w. Epub 2020 Jun 18. — View Citation

Steinberger S, Lin B, Bernheim A, Chung M, Gao Y, Xie Z, Zhao T, Xia J, Mei X, Little BP. CT Features of Coronavirus Disease (COVID-19) in 30 Pediatric Patients. AJR Am J Roentgenol. 2020 Dec;215(6):1303-1311. doi: 10.2214/AJR.20.23145. Epub 2020 May 22. — View Citation

Ziegler CGK, Allon SJ, Nyquist SK, Mbano IM, Miao VN, Tzouanas CN, Cao Y, Yousif AS, Bals J, Hauser BM, Feldman J, Muus C, Wadsworth MH 2nd, Kazer SW, Hughes TK, Doran B, Gatter GJ, Vukovic M, Taliaferro F, Mead BE, Guo Z, Wang JP, Gras D, Plaisant M, Ansari M, Angelidis I, Adler H, Sucre JMS, Taylor CJ, Lin B, Waghray A, Mitsialis V, Dwyer DF, Buchheit KM, Boyce JA, Barrett NA, Laidlaw TM, Carroll SL, Colonna L, Tkachev V, Peterson CW, Yu A, Zheng HB, Gideon HP, Winchell CG, Lin PL, Bingle CD, Snapper SB, Kropski JA, Theis FJ, Schiller HB, Zaragosi LE, Barbry P, Leslie A, Kiem HP, Flynn JL, Fortune SM, Berger B, Finberg RW, Kean LS, Garber M, Schmidt AG, Lingwood D, Shalek AK, Ordovas-Montanes J; HCA Lung Biological Network. Electronic address: lung-network@humancellatlas.org; HCA Lung Biological Network. SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues. Cell. 2020 May 28;181(5):1016-1035.e19. doi: 10.1016/j.cell.2020.04.035. Epub 2020 Apr 27. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Functional lung assessment (LF-MRI)	Change in functional lung parameters	Baseline compared to 6 months
Secondary	Morphologic lung assessment (LF-MRI)	Morphologic changes in lung parenchyma	Baseline compared to 6 months
Secondary	Cardiological functional diagnostics (VO2)	Oxygen uptake (VO2)	Baseline compared to 6 months
Secondary	Cardiological functional diagnostics (VO2max)	Peak oxygen uptake (VO2max)	Baseline compared to 6 months
Secondary	Cardiological functional diagnostics (VT2)	Ventilatory anaerobic threshold (VT2)	Baseline compared to 6 months
Secondary	Cardiological functional diagnostics (VCO2)	Carbon dioxide output (VCO2)	Baseline compared to 6 months
Secondary	Cardiological functional diagnostics (HR)	Heart rate (HR)	Baseline compared to 6 months
Secondary	Cardiological functional diagnostics (HRR)	Heart Rate Reserve (HRR)	Baseline compared to 6 months
Secondary	Cardiological functional diagnostics (Breath rate at VAT)	Breath rate at VAT	Baseline compared to 6 months
Secondary	Cardiological functional diagnostics (BRR)	Breath rate reserve (BRR)	Baseline compared to 6 months
Secondary	Cardiological functional diagnostics (VE)	Minute ventilation (VE)	Baseline compared to 6 months
Secondary	Cardiological functional diagnostics (O2Pulse)	O2Pulse	Baseline compared to 6 months
Secondary	Cardiological functional diagnostics (HRV)	Heart rate variability (HRV)	Baseline compared to 6 months
Secondary	Cardiological functional diagnostics (Borg Scale)	Exercise capacity nach Borg Scale	Baseline compared to 6 months
Secondary	Cardiological functional diagnostics (BGA)	Capillary blood gas and lactate (BGA)	Baseline compared to 6 months
Secondary	Nailfold capillaroscopy (capillaries)	Number of capillaries in first row	Baseline compared to 6 months
Secondary	Nailfold capillaroscopy (first row)	Number of capillaries in first row	Baseline compared to 6 months
Secondary	Nailfold capillaroscopy (morphology)	Morphology of capillaries	Baseline compared to 6 months
Secondary	Blood sample (antibodies)	SARS-CoV2-antibodies	Baseline compared to 6 months
Secondary	Blood sample (auto antibodies)	Autoantibodies against G-protein receptors	Baseline compared to 6 months
Secondary	Blood sample (RT-DC)	Realtime deformability cytometry	Baseline compared to 6 months
Secondary	Blood sample (Blood count)	Blood count	Baseline compared to 6 months
Secondary	Blood sample (IL-6)	Interleukin-6 (IL-6)	Baseline compared to 6 months
Secondary	Blood sample (CrP)	C-reactive proteine (CrP)	Baseline compared to 6 months
Secondary	Blood sample (Calpro)	Calprotectin (Calpro)	Baseline compared to 6 months
Secondary	Blood sample (Coagulation)	Coagulation factors (Coagulation)	Baseline compared to 6 months