The Roles of Vitamin D and Microbiome in Children With Post-acute COVID-19 Syndromes (PACS) and Long COVID

• ClinicalTrials.gov Identifier: NCT05633472
• Recruitment Status: Recruiting
• First Posted: December 1, 2022
• Last Update Posted: February 7, 2024
• Sponsor: China Medical University Hospital
• Information provided by (Responsible Party): China Medical University Hospital

Tracking Information

• First Submitted Date: November 30, 2022
• First Posted Date: December 1, 2022
• Last Update Posted Date: February 7, 2024
• Actual Study Start Date: October 18, 2022
• Estimated Primary Completion Date: September 30, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 1, 2022)

• Levels of vitamin D [ Time Frame: Month 0 ]
  Vitamin D will be measured in a blood sample by ELISA to determine baseline status.
• Levels of vitamin D [ Time Frame: Month 6 ]
  Vitamin D will be measured in a blood sample to follow the change from baseline in vitamin D level at month 6.
• Single nucleotide polymorphism of vitamin D receptor and vitamin D binding protein [ Time Frame: Month 0 ]
  Single nucleotide polymorphism (SNP) genotyping will be performed in a blood sample by using TaqMan SNP genotyping assays.
• Microbiome [ Time Frame: Month 0 ]
  Nasal and anal swabs will be used to detect respiratory and intestinal microbiome by using 16S rRNA sequencing to determine baseline status.
• Microbiome [ Time Frame: Month 6 ]
  Nasal and anal swabs will be used to detect respiratory and intestinal microbiome by using 16S rRNA sequencing,and to follow the change from baseline in microbiome at month 6.
• Total immunoglobulin E (IgE) [ Time Frame: Month 0 ]
  Plasma total IgE concentration will be measured by microparticle immunoassay (IMx analyzer, Abbott Laboratories, Abbott Park, IL) and ELISA to determine baseline status.
• Total immunoglobulin E (IgE) [ Time Frame: Month 6 ]
  Plasma total IgE concentration will be measured by microparticle immunoassay (IMx analyzer, Abbott Laboratories, Abbott Park, IL) and ELISA to follow the change from baseline in total IgE at month 6.
• Allergen-specific immunoglobulin E (IgE) [ Time Frame: Month 0 ]
  Plasma allergen-specific IgE will be measured by BioIC ®.

Original Primary Outcome Measures (submitted: November 30, 2022)

• Levels of vitamin D [ Time Frame: Month 0 ]
  Vitamin D will be measured in a blood sample by ELISA to determine baseline status.
• Levels of vitamin D [ Time Frame: Month 6 ]
  Vitamin D will be measured in a blood sample to follow the change from baseline in vitamin D level at month 6.
• Single nucleotide polymorphism of vitamin D receptor and vitamin D binding protein [ Time Frame: Month 0 ]
  Single nucleotide polymorphism (SNP) genotyping will be performed in a blood sample by using TaqMan SNP genotyping assays.
• Microbiome Microbiome [ Time Frame: Month 0 ]
  Nasal and anal swabs will be used to detect respiratory and intestinal microbiome by using 16S rRNA sequencing to determine baseline status.
• Microbiome Microbiome [ Time Frame: Month 6 ]
  Nasal and anal swabs will be used to detect respiratory and intestinal microbiome by using 16S rRNA sequencing,and to follow the change from baseline in microbiome at month 6.
• Total IgE [ Time Frame: Month 0 ]
  Plasma total IgE concentration will be measured by microparticle immunoassay (IMx analyzer, Abbott Laboratories, Abbott Park, IL) and ELISA to determine baseline status.
• Total IgE [ Time Frame: Month 6 ]
  Plasma total IgE concentration will be measured by microparticle immunoassay (IMx analyzer, Abbott Laboratories, Abbott Park, IL) and ELISA to follow the change from baseline in total IgE at month 6.
• Allergen-specific IgE [ Time Frame: Month 0 ]
  Plasma allergen-specific IgE will be measured by BioIC ®.

Current Secondary Outcome Measures (submitted: November 30, 2022)

• Children's Somatic Symptoms Inventory (CSSI) [ Time Frame: Month 0 to Month 6 ]
  CSSI. Range (0-4); lower scores indicate better health
• KINDL questionnaire [ Time Frame: Month 0 to Month 6 ]
  For assessing Health-Related Quality of Life in children and adolescents aged 3 years and older.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: The Roles of Vitamin D and Microbiome in Children With Post-acute COVID-19 Syndromes (PACS) and Long COVID
• Official Title: The Roles of Vitamin D and Microbiome in Children With Post-acute COVID-19 Syndromes (PACS) and Long COVID
• Brief Summary: A double-blind study to evaluate the role of human microbiome and vitamin D in the development of long COVID and PACS in children.
• Detailed Description: Children worldwide are at risk of SARS-CoV-2 infection because of a lack of approved vaccines for children aged 0-4 years. Moreover, SARS-CoV-2 infected children also suffered with long term sequels of virus infection, which involved multiple organs, such as fatigue, post-exercise malaise, skeletal muscular pains, headache, palpitation and insomnia. In fact, there is limited evidence available on the long-term impact of SARS-CoV-2 infection in children. Recent studies have shown critical-ill COVID-19 patients suffered with low vitamin D concentration and microbiome dysbiosis in their respiratory and gastrointestinal system. Vitamin D has been known to counteract several respiratory virus infections as well as beneficial functions in multiple organs. Also, commensal microbiota in lung and intestinal tracts exert protective functions against virus infections and, through its metabolite and axis links, has anti-inflammatory actions and homeostasis in multiple organs. Hence, in this study, the investigators hypothesis that long COVID or post-acute COVID syndrome (PACS) in children is due to the effect of post-virus infection on the immuno-metabolism change (vitamin D deficiency) and perturbation of gut microbiota (microbiome dysbiosis), therefore our study aims are first, make the comparisons of vitamin D levels and respiratory and gut microbiome between symptomatic and non-symptomatic post-COVID children using cross-sectional study. Next, for interventional study, patients will be divided in two groups to receive supplementation of vitamin D or placebo for 6 months to evaluate the effect of vitamin D on the symptoms relieve and improvement of microbiome dysbiosis in post-acute COVID syndrome (PACS) children. The investigators expect through this study, the investigators can learn more on the pathogenesis and the effect of vitamin D and microbiota in long COVID and PACS in children.
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Post-acute COVID-19 Syndromes

Intervention

• Other: Vitamin D
  Vitamin D (2000IU/day) for 6 months
• Other: Placebo
  Placebo

Study Arms

• Experimental: Experimental: Treatment group
  Vitamin D (2000IU/day) for 6 months
  Intervention: Other: Vitamin D
• Placebo Comparator: Placebo Comparator: Control group
  placebo
  Intervention: Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 30, 2022): 150
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 30, 2025
• Estimated Primary Completion Date: September 30, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Children aged 0-18 years
2. The child sought/needed primary or secondary medical care for COVID-19
3. Laboratory (RT-PCR, COVID-19 antigen tests or SARS-CoV-2 antibody testing) or physician confirmed SARS-CoV-2 infection based on classic clinical symptoms and/or ground-glass opacification on CT imaging.
4. 28 days - 3 months from the onset of COVID-19 symptoms
5. Parent's/carer's/guardians consent to participate

Exclusion Criteria:

1. Recruit patients who have used antibiotics, systemic steroids, and immunosuppressants in the previous month.
2. Patients with C1 esterase inhibitor deficiency, lymphocytopenia, thrombocytopenia, severe diseases involving heart, liver, or kidney, metabolic disease, or autoimmune disease.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 0 Years to 18 Years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Jiu-Yao Wang, MD; 886422052121 ext 4131; aim.cmuh@gmail.com

• Listed Location Countries: Taiwan

Administrative Information

• NCT Number: NCT05633472
• Other Study ID Numbers: CMUH111-REC2-122
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: China Medical University Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: China Medical University Hospital
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: China Medical University Hospital
• Verification Date: February 2024