Adolescents With COVID-19/MIS-C at HCFMUSP

Covid19 Clinical Trial

Official title:

Prospective Studies in School-aged Children and Adolescents With COVID-19 Treated at HCFMUSP

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04659486
• Other study ID #: 37460620.8.0000.0068
• Status: Enrolling by invitation
• Phase: N/A
• Start date: September 24, 2020
• Est. completion date: April 30, 2021

Study information

• Verified date: December 2020
• Source: University of Sao Paulo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a protocol aimed at children and adolescents contaminated with COVID, treated at the Hospital das Clínicas, University of Sao Paulo, Brazil (HCFMUSP), in the recovery phase. The study aims to evaluate the spectrum of pathogenic lesions of the virus not only in the respiratory system, but digestive, immunological, neurological and others. Clinical, evolutionary, laboratory and functional parameters will be used.

Description:

School-age children and adolescents COVID-19 survivors may have persistent inflammation, a chronic course of COVID-19, with isolated or concomitant aggressions of various organs and systems, making this disease a potential chronic condition, impacting aspects of quality of life related to health (HRQoL), physical and mental health. In addition, pediatric COVID-19 can induce autoimmunity (with the possibility of primary hypothyroidism and type I diabetes mellitus), delayed linear growth and delayed pubertal development, secondary immunodeficiency and present genetic polymorphisms in brain plasticity impacting rehabilitation. School-aged children and adolescents with COVID-19 could present muscle weakness, dysautonomy, asthenia and physical inactivity, so it is essential that safe and effective interventions are developed to maintain adequate levels of physical activity and that they can be implemented on a large scale. However, to date, there are no systematic longitudinal studies that have evaluated all these aspects in a pediatric population that survived COVID-19, particularly with chronic conditions and who were hospitalized in a tertiary service.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 100
• Est. completion date: April 30, 2021
• Est. primary completion date: April 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 7 Years to 18 Years

Eligibility

Inclusion Criteria:

• school-age children and adolescents diagnosed with COVID-19

Exclusion Criteria:

• school-age children and adolescents with MIS-C, who present: myocardial dysfunction, refractory cardiac arrhythmias, coronary artery aneurysms with or without thrombi, electrocardiographic alterations suggestive of myocardial infarction or ischemia and clinical signs of heart failure;
• presence of any limitation or physical disability that prevents the practice of exercise;
• pregnancy.

Related Conditions & MeSH terms

• Communicable Diseases
• Corona Virus Infection
• Coronavirus Infections
• Covid19
• Infection
• SARS (Severe Acute Respiratory Syndrome)
• SARS-CoV Infection
• Severe Acute Respiratory Syndrome

Intervention

Behavioral:
• Home-based exercise training
Online strength and aerobic home-based exercise training, 3 times per week, for 12 weeks. The exercise program is composed by 2 intensity-levels (starter and advanced).

Locations

Country	Name	City	State
Brazil	Hospital das Clinicas Faculdade de Medicina USP	Sao Paulo	SP

Sponsors (3)

Lead Sponsor	Collaborator
University of Sao Paulo	Fundação de Amparo à Pesquisa do Estado de São Paulo, Hospital das Clínicas da Faculdade de Medicina da USP

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Quality of Life assessed by the Pediatric Quality of Life Inventory (Peds-QoL)	The instrument was translated and validated for the Brazilian population	Change from Baseline at 3 months
Primary	Quality of Life assessed by the Pediatric Quality of Life Inventory (Peds-QoL)	The instrument was translated and validated for the Brazilian population	Change from Baseline at 6 months
Secondary	Flow-volume loop assessed by spirometry	Aims to investigate the mechanisms that lead to dyspnea and, consequently, intolerance to physical effort	Baseline, 3 months, 6 months
Secondary	Health-related quality of life assessed by the Pediatric Outcomes Data Collection Instrument	It will also be assessed for school-age children (7-10 years old) and adolescents (11-18 years old) and by their primary caregiver	Baseline, 3 months, 6 months, 12 months
Secondary	Complete blood count (hemoglobin, leukocyte, lymphocyte and platelet count)		Baseline, 3 months, 6 months, 12 months
Secondary	Inflammatory markers (C-reactive protein, fibrinogen, D-dimer and ferritin);		Baseline, 3 months, 6 months,12 months
Secondary	Lactate dehydrogenase		Baseline, 3 months, 6 months, 12 months
Secondary	Aspartate and alanine aminotransferase		Baseline, 3 months, 6 months, 12 months
Secondary	Serum urea and creatinine		Baseline, 3 months, 6 months, 12 months
Secondary	Triglycerides		Baseline, 3 months, 6 months, 12 months
Secondary	Creatinine phosphokinase (CK)		Baseline, 3 months, 6 months, 12 months
Secondary	Amilase		Baseline, 3 months, 6 months, 12 months
Secondary	Lipase		Baseline, 3 months, 6 months, 12 months
Secondary	Troponin T		Baseline, 3 months, 6 months, 12 months
Secondary	Pro-BNP		Baseline, 3 months, 6 months, 12 months
Secondary	Lung abnormalities will be assessed by pulmonary computed tomography	Patchy ground-glass opacities, crazy-paving pattern, and localization and pattern of large, confluent or small nodular lesions will be assessed	Baseline, 3 months, 6 months, 12 months
Secondary	Systolic and diastolic function will be assessed by echocardiogram	Conventional transthoracic echocardiogram with color Doppler to assess systolic and diastolic function	Baseline, 3 months, 6 months, 12 months
Secondary	Valve dysfunction will be assessed by echocardiogram	Conventional transthoracic echocardiogram with color Doppler to search for valve dysfunction	Baseline, 3 months, 6 months, 12 months
Secondary	Pericardial effusion will be assessed by echocardiogram	Conventional transthoracic echocardiogram with color Doppler to search for pericardial effusion	Baseline, 3 months, 6 months, 12 months
Secondary	Coronary arteries will be assessed by echocardiogram	Conventional transthoracic echocardiogram with color Doppler to search for aspects of the coronary arteries	Baseline, 3 months, 6 months, 12 months
Secondary	Ischemia will be assessed by echocardiogram	Echocardiogram with two-dimensional speckle-tracking technique to identify subclinical changes suggestive of ischemia or myocarditis	Baseline, 3 months, 6 months, 12 months
Secondary	Immunocompetence, including thymic function	Baseline levels of cytokines IL-2, IL-4, IL-6, IL-10, TNF-alpha, IFN-y, and IL-17A in serum samples will be tested by flow cytometry using the CBA technique (Cytometric bead array, BD Biosciences)	Baseline, 3 months, 6 months, 12 months
Secondary	Leukogram will be assessed by leukocyte and lymphocyte counts		Baseline, 3 months, 6 months,, 12 months
Secondary	Immunophenotyping of lymphocytes T cell lineages will be evaluated by flow cytometry	T cell lineages: CD3CD4, CD3CD8, naive cells (CD45RA+), memory cells (CD45RA-), effector cells (CD38+HLADR+)	Baseline, 3 months, 6 months, 12 months
Secondary	Immunophenotyping of lymphocytes B cell lineages will be evaluated by flow cytometry	B cell lineages: CD19, naive cells (CD27-), memory cells (CD27+), plasmablasts (CD27+CD38+CD138-), (plasmocytes CD27+CD38+CD138+)	Baseline, 3 months, 6 months, 12 months
Secondary	Immunophenotyping of lymphocytes NK cells will be evaluated by flow cytometry	NK cells: (CD3-CD16+CD56+), degranulated: CD107a+	Baseline, 3 months, 6 months, 12 months
Secondary	Serum levels of anti-Streptococcus pneumoniae IgG antibodies		Baseline, 3 months, 6 months, 12 months
Secondary	Anti-pneumococcal vaccine response will be assessed by ELISA	The antipneumococcal antibody titer against 6 polysaccharides (serotypes 1, 5, 6B, 9V, 14, and 18C) will be analyzed by ELISA. The seroconversion criteria is IgG values > 1.3 mg/mL for each polysaccharide assessed	Baseline, 3 months, 6 months, 12 months
Secondary	Evaluation of the thymus by the determination of TRECs (Thymic recent emigrant cells or T-cell receptor excision circles)	TRECs evaluate the peripheral function of the thymus from cells that have recently been released, using the RT-PCR technique	Baseline, 3 months, 6 months, 12 months
Secondary	Changes in frequency of the autoantibodies of the thyroid gland	(anti-thyroperoxidase antibodies, anti-thyroglobulin)	Baseline, 3 months, 6 months, 12 months
Secondary	Changes in frequency of the anti-GAD antibody will be assessed using immunoprecipitation		Baseline, 3 months, 6 months, 12 months
Secondary	Changes in frequency of the anti-islet antibody of Langerhans will be assessed using indirect fluorescence		Baseline, 3 months, 6 months, 12 months
Secondary	Changes in frequency of the anti-insulin antibody will be assessed by radioimmunoassay		Baseline, 3 months, 6 months, 12 months
Secondary	Diagnosis of thyroid dysfunction will be assessed by thyroid profile (TSH, free T4 and T3)		Baseline, 3 months, 6 months, 12 months
Secondary	Diagnosis of type 1 diabetes mellitus will be assessed by the metabolic profile (fasting glucose, glycated hemoglobin and C peptide)		Baseline, 3 months, 6 months,, 12 months
Secondary	Linear growth will be assessed by using a standardized stadiometer, calculating standard deviation, growth curves, and growth speed		Baseline, 3 months, 6 months, 12 months
Secondary	Development of puberty will be assessed according to the criteria of Tanner and Marshall in adolescents in the prepubertal age group		Baseline, 3 months, 6 months, 12 months
Secondary	Bone age will be assessed using non-dominant hand and wrist radiography		Baseline, 12 months
Secondary	Bone mineral density will be assessed by Bone densitometry (DXA) in the region of the lumbar spine		Baseline, 3 months, 6 months, 12 months
Secondary	Bone mineral content will be assessed by Bone densitometry (DXA) in the region of the lumbar spine		Baseline, 3 months, 6 months, 12 months
Secondary	Bone mineral density will be assessed by Bone densitometry (DXA) in the proximal femur		Baseline, 3 months, 6 months, 12 months
Secondary	Bone mineral content will be assessed by Bone densitometry (DXA) in the proximal femur		Baseline, 3 months, 6 months, 12 months
Secondary	Bone mineral density will be assessed by Bone densitometry (DXA) in the whole body		Baseline, 3 months, 6 months, 12 months
Secondary	Bone mineral content will be assessed by Bone densitometry (DXA) in the whole body		Baseline, 3 months, 6 months, 12 months
Secondary	Body composition (visceral adipose tissue) will be assessed by Bone densitometry		Baseline, 3 months, 6 months, 12 months
Secondary	Body composition (lean mass) will be assessed by Bone densitometry		Baseline, 3 months, 6 months, 12 months
Secondary	Body composition (fat mass) will be assessed by Bone densitometry		Baseline, 3 months, 6 months, 12 months
Secondary	Bone biochemical and bone remodeling markers (calcium, phosphorus, 25OH alkaline phosphatase vitamin D, PTH, CTX, P1NP)		Baseline, 3 months, 6 months, 12 months
Secondary	Pediatric gait assessment will be assessed by an Actigraph (3D accelerometer) model G-Walk used during the "timed up and go" test		Baseline, 3 months, 6 months, 12 months
Secondary	Pediatric gait assessment will be assessed by an Actigraph (3D accelerometer) model G-Walk during the 6-minute walk test		Baseline, 3 months, 6 months, 12 months
Secondary	Pediatric gait assessment will be assessed by an Actigraph (3D accelerometer) model G-Walk during the 10 meter gait test		Baseline, 3 months, 6 months, 12 months
Secondary	Pediatric gait assessment will be assessed by musculoskeletal ultrasound		Baseline, 3 months, 6 months, 12 months
Secondary	Genetic Polymorphism Analysis will be assessed by salting out methodology followed by q-PCR (Real-time PCR) using the TaqMan assay using Step One Plus equipment	According to the gene sequence studied, the analysis will be performed using the Sanger sequencing technique with capillary electrophoresis in a 3130 automatic sequencer (Applied Biosystems).; The genetic polymorphisms of the ABO system gene (rs505922), two polymorphisms of the OPRM1 gene (rs1799971 and rs1799972) and a polymorphism of the BDNF gene (rs6265) will be investigated, with possible contributions to the risk of impaired gait.	Baseline, 3 months, 6 months, 12 months
Secondary	Mental health will be assessed by the "Strengths and Weaknesses of Attention-deficit/hyperactivity disorder (ADHD) symptoms and Normal behaviors"	This is an 18-item parent questionnaire for children and adolescents (18 years and younger). This rating scale includes positive "weaknesses" and negative "strengths" scoring, assessing symptoms of Attention-Deficit/Hyperactivity Disorder. Parents are asked to compare their child's behavior in a variety of settings over the past month to other children on a 7-point: 3-Far below, 2-Below, 1-Slightly below, 0-Average, -1-Slightly average, -2-Above, -3-Far above. Higher scores indicate greater symptomology	Baseline, 3 months, 6 months, 12 months
Secondary	Mental health will be assessed by the "Strengths and Difficulties Questionnaire"	The Strengths and Difficulties Questionnaire (SDQ) is a brief behavioural screening questionnaire, and includes 25 items on psychological attribute: emotional symptoms (5 items), conduct problems (5 items) hyperactivity/inattention (5 items), peer relationship problems (5 items), prosocial behaviour (5 items). Higher scores indicate greater difficulties	Baseline, 3 months, 6 months, 12 months
Secondary	Mental health will be assessed by the "Depression, Anxiety and Stress Scale"	The Depression, Anxiety and Stress Scale - 21 Items (DASS-21) is a set of three self-report scales designed to measure the emotional states of depression, anxiety and stress (7 items each subscale). Patients are asked to score every item on a scale from 0 (did not apply to me at all) to 3 (applied to me very much). Sum scores for the total DASS-total scale range between 0 and 120. Scores =60 (for DASS-total) and =21 (for the depression subscale) are labeled as "high" or "severe".	Baseline, 3 months, 6 months, 12 months
Secondary	Physical activity levels assessed by ActivPAL	ActivPAL will be used for 7 days for at least 10 hours/day	Baseline, 3 months, 6 months, 12 months
Secondary	Food consumption levels assessed by food records	24-hour recalls will be assessed on three non-consecutive days (two weekdays, and one weekend). Online Dietbox will be used.	Baseline, 3 months, 6 months, 12 months
Secondary	Blood flow will be assessed using a Doppler Ultrasound	Baseline blood flow measurements will be assessed in the brachial artery	Baseline, 3 months, 6 months, 12 months
Secondary	Endothelial function will be assessed using a Doppler Ultrasound	Flow-mediated vasodilation (VMF) will be assessed in the brachial artery	Baseline, 3 months, 6 months, 12 months