Clinical trial NCT02388516: Maternal Vitamin D for Acute Respiratory Infections in Infancy
Official title: Maternal Vitamin D for Acute Respiratory Infections in Infancy (MDARI): a Nested Sub-study in a Randomized Controlled Trial of Vitamin D Supplementation During Pregnancy and Lactation in Dhaka, Bangladesh
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Upper Respiratory Tract Infections
Lower Respiratory Tract Infections
Keywords: Bangladesh
Vitamin D
Acute Respiratory Infections
Infancy
Pregnancy
Lead sponsor: The Hospital for Sick Children
Sponsor class: OTHER
Collaborators: name: International Centre for Diarrhoeal Disease Research, Bangladesh
First posted: 2015-03-17
Enrollment: 1214
Sex: ALL
Minimum age (years): 1
Maximum age (years): 26
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: There is a growing body of data suggesting that vitamin D modulates the host's immune response to acute respiratory infection (ARI). The primary aim of this study is to determine whether maternal vitamin D3 supplementation versus placebo decreases the incidence rate of microbiologically confirmed viral-associated ARI among infants in Dhaka, Bangladesh. Secondary outcomes include: A) incidence of ARI associated with specific major pathogens, B) incidence of clinical ARI (without the need for positive microbiology), and C) quantitative density of pneumococcal carriage. Infants will be followed from birth until 6 months of life. Among infants who meet at least one of the specific case definitions for ARI (see 'Detailed Description' section), nasal swab specimens will be collected. Respiratory samples will be analyzed by real-time polymerase chain reaction (qPCR) to identify a 7-virus panel (influenza A and B, respiratory syncytial virus, human metapneumovirus, adenovirus, and parainfluenza types 1, 2, and 3) plus quantitative density of S. pneumonia.

Detailed description: In this study, an acute respiratory infection (URTI and/or LRTI) has been clinically defined as:

A) Upper respiratory tract infection (URTI)

A new-onset illness consisting of at least two of the following clinical criteria at any time during a surveillance week:

* Caregiver-reported cough;
* Caregiver-reported rhinorrhea;
* Caregiver-reported nasal congestion; and,
* Measured axillary temperature greater than or equal to 37.5°C.

B) Lower respiratory tract infection (LRTI)

1. New onset clinically-diagnosed LRTI:

   * Caregiver-reported cough AND/OR difficulty breathing during a surveillance week; AND,
   * Observed lower chest wall indrawing AND/OR elevated respiratory rate (60 breaths per minute or greater for infant up to 59 days of age, or 50 breaths per minute or greater for infant 60 days of age or older)
2. Hospitalized LRTI

   * Hospitalization with physician diagnosis of pneumonia or bronchiolitis

Eligibility criteria: Inclusion Criteria:

* Infants born to women enrolled in the MDIG trial (NCT01924013).
* Maternal inclusion criteria (at time of enrolment) will be:
* At least 18 years of age
* 17 to 24 completed weeks of gestation
* Intends to permanently reside in the trial catchment area for at least 18 months
* Family plans to reside in catchment area for the first 6 months postnatal
* Provides written informed consent for participation

Exclusion Criteria:

* Mother withdrawn from MDIG trial prior to delivery
* Failure to provide consent for participation in sub-study

Primary outcomes:
measure: Microbiologically confirmed viral acute respiratory infection (URTI and/or LRTI)
timeFrame: 0 to 6 months
Secondary outcomes:
measure: ARI with microbiologically confirmed influenza A or B
timeFrame: 0 to 6 months
measure: ARI with microbiologically confirmed RSV
timeFrame: 0 to 6 months
measure: Clinical URTI and/or LRTI (i.e., no microbiological confirmation)
timeFrame: 0 to 6 months
measure: Clinical URTI (i.e., no microbiological confirmation)
timeFrame: 0 to 6 months
measure: Clinical LRTI (i.e., no microbiological confirmation)
timeFrame: 0 to 6 months
measure: Quantitative S. pneumoniae nasal carriage density
timeFrame: 0 to 6 months
measure: Pneumonia (non-severe) and severe pneumonia or very severe disease
timeFrame: 2 to 6 months
Other outcomes:
Locations:
city: Dhaka
country: Bangladesh
facility: International Centre for Diarrhoeal Disease Research, Bangldesh
Study officials:
affiliation: The Hospital for Sick Children
name: Shaun K Morris, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: The Hospital for Sick Children
name: Daniel Roth, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Taghivand M, Pell LG, Rahman MZ, Mahmud AA, Ohuma EO, Pullangyeum EM, Ahmed T, Hamer DH, Zlotkin SH, Gubbay JB, Morris SK, Roth DE. Effect of maternal vitamin D supplementation on nasal pneumococcal acquisition, carriage dynamics and carriage density in infants in Dhaka, Bangladesh. BMC Infect Dis. 2022 Jan 13;22(1):52. doi: 10.1186/s12879-022-07032-y.
citation: Morris SK, Pell LG, Rahman MZ, Dimitris MC, Mahmud A, Islam MM, Ahmed T, Pullenayegum E, Kashem T, Shanta SS, Gubbay J, Papp E, Science M, Zlotkin S, Roth DE. Maternal vitamin D supplementation during pregnancy and lactation to prevent acute respiratory infections in infancy in Dhaka, Bangladesh (MDARI trial): protocol for a prospective cohort study nested within a randomized controlled trial. BMC Pregnancy Childbirth. 2016 Oct 13;16(1):309. doi: 10.1186/s12884-016-1103-9.