Clinical trial NCT00063596: Vitamin A Supplementation in Preterm Infants
Official title: Vitamin A Therapy in Preterm Infants: Vaccine Response
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Infant, Premature
Keywords: Vitamin A
Hepatitis B vaccine
Immune responses
T-cell subsets
Chronic lung disease
Cytokines, intracytoplasmic
Antibodies, hepatitis B and tetanus toxoid
Lead sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Sponsor class: NIH
First posted: 2003-07-02
Enrollment: 220
Sex: ALL
Minimum age (years): 1
Maximum age (years): 3
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Extremely low birth weight infants have decreased blood levels of Vitamin A. This Vitamin A deficiency may increase the risk of infections and chronic lung disease in these infants. This study will examine the effects of Vitamin A supplementation in premature babies born weighing less than 1500 grams (3.3 lbs).

Detailed description: Vitamin A and its derivative retinoic acid (RA) have been recognized as important factors in potentiating the immune response and protecting against infection. In developing nations, Vitamin A deficiency is associated with infectious gastroenteritis and increased susceptibility to a number of infections, such as measles. RA is an important regulator of cell growth and differentiation and can augment IgM production from core blood mononuclear cells in response to a polyclonal B-cell activator. This augmentation in immunoglobulin secretion is mediated by the effects of RA on both T and B cells, in part through the production of certain cytokines (e.g., IL-6 and IL-10) important in the terminal differentiation of B-cells to plasma cells. In animal models, correction of Vitamin A deficiency improves immune response to vaccination.

Infants with extremely low birth weight have low plasma and tissue concentrations of Vitamin A. Vitamin A supplementation of pre-term infants reduces chronic lung disease and the risk of sepsis. Because the immune system of the pre-term infant is immature, the response of pre-term infants to Hepatitis B vaccine is diminished compared to full-term babies. This study will determine whether Vitamin A supplementation of pre-term infants will enhance the response of these infants to immunization with Hepatitis B vaccine. The study will also evaluate the effect of Vitamin A supplementation on survival, chronic lung disease, and infection rate.

Low birth weight pre-term infants will be randomized to receive either Vitamin A supplementation or placebo. The Vitamin A treatment group will receive 5,000 IU of Vitamin A (retinyl palmitate) by intramuscular injection 3 times weekly for 28 days starting on postnatal day 2. To avoid pain and discomfort, the placebo group will receive a sham procedure rather than a placebo saline injection. The staff of the neonatal intensive care unit will retain the responsibility for decisions regarding the use of other therapies, such as parental fluids, mechanical ventilation, glucocorticoids, hyperalimentation, and blood replacement. All infants will be assessed for potential Vitamin A toxicity. While in the neonatal intensive care unit, infants will have blood tests at Days 0, 14, 30, and 60. After discharge from the neonatal intensive care unit, patients return for clinic assessment and blood samples at Months 4, 6, and 9. Infants will be given Hepatitis B vaccine at 2, 4, and 6 months chronological age. Primary outcome measures will include Hepatitis B antibody levels, chronic lung disease, rate of infection while in the neonatal intensive care unit, and the incidence and severity of infections during the first 9 months of life.

Eligibility criteria: Inclusion Criteria

* Born at less than 32 weeks gestation
* Weigh less than 1500 g (3.3 lbs) and more than 500 g (1.1 lbs)

Primary outcomes:
measure: Response to Hepatitis B vaccine
Secondary outcomes:
measure: Chronic lung disease
measure: Length of hospital stay
measure: Respiratory and GI infections to 9 months of age
measure: T-cell cytokine production and development
measure: T-cell subset development
Other outcomes:
Locations:
city: Buffalo
country: United States
facility: Women's and Children's Hospital of Buffalo
state: New York
Study officials:
affiliation: State University of New York at Buffalo
name: Mark Ballow, MD
role: PRINCIPAL_INVESTIGATOR
References: