Trial record 1 of 1 for:    NCT01476358
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Effect of Vitamin A Supplementation on Immune Responses in Human Neonates (NNVAS)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
World Health Organization
Information provided by (Responsible Party):
London School of Hygiene and Tropical Medicine
ClinicalTrials.gov Identifier:
NCT01476358
First received: November 9, 2011
Last updated: November 12, 2012
Last verified: November 2012
  Purpose

Vitamin A supplementation (VAS) significantly reduces all-cause mortality when given after 6 months of age, but has a null or detrimental effect when given between 1-5 months. Studies of neonatal VAS (NNVAS) have produced conflicting findings. These age-pattern variations might result from immunological interactions between VAS and vaccines. The potential efficacy of NNVAS is being retested in 3 large new intervention trials with mortality as endpoint. Complementary mechanistic studies in animals and in human infants in The Gambia (this proposal) and Bangladesh have been commissioned to run in parallel.

The investigators will use a 2-arm double blind RCT to test whether NNVAS modulates the early ontogeny of human immune development. Neonates, recruited through a peri-urban clinic in The Gambia, will receive either 50,000 International Units (IU) VAS orally within 48 hours of birth (intervention group, n=100) or a placebo (control group, n=100). Male and female neonates will be randomized separately at enrolment for later analyses by sex. All infants will be followed up from birth to age 1 year. A broad panel of immunological outcomes will examine whether NNVAS: a). normalises thymic development (thymic index by ultrasound); b). skews mycobacterial and recall antigen responses towards a Th2 profile; c). diminishes Th1 and Th17 reactivity to mycobacterial and recall antigens; d). diminishes the tuberculin skin test (TST) response; e). causes increased innate immune reactivity; f). increases the frequency of circulating regulatory T cells (Tregs) expressing gut homing receptors; g). enhances B cell immune responses after routine vaccination (increase of B cell numbers and activation status); h). increases circulating IgA in mucosal immune compartment, especially oral polio vaccine (OPV) specific IgA post-vaccination; i). decreases bacterial translocation, by improving mucosal barrier function; and j). decreases markers of infection or inflammation. Growth and morbidity will also be assessed.


Condition Intervention Phase
Vitamin A Deficiency
Dietary Supplement: Vitamin A (retinyl palmitate).
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Official Title: A Randomized Controlled Trial in Human Neonates to Determine the Effect of Vitamin A Supplementation on Immune Responses

Resource links provided by NLM:


Further study details as provided by London School of Hygiene and Tropical Medicine:

Primary Outcome Measures:
  • Frequency of circulating Tregs expressing gut homing receptors in infant participants. [ Time Frame: 17 week post-supplementation ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Difference in Thymus size in infant participants [ Time Frame: 1, 6, 12 and 17 weeks ] [ Designated as safety issue: No ]
    Assessed by ultrasonic analysis.

  • Difference in B cell immune responses after routine vaccination in infant participants [ Time Frame: 6 and 17 weeks ] [ Designated as safety issue: No ]
    Assessed as an increase in B cell numbers and activation status.

  • Improved mucosal barrier function in infant participants [ Time Frame: 6 and 17 weeks ] [ Designated as safety issue: No ]
    Assessed by quantifying bacterial translocation into the blood.


Estimated Enrollment: 200
Study Start Date: November 2011
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Vitamin A
Capsule containing oil vehicle with Vitamin A (retinyl palmitate). Capsules are prepared by the manufacturer (Strides Arcolab Limited, India) and assigned blinded codes by World Health Organization officials.
Dietary Supplement: Vitamin A (retinyl palmitate).

Active Comparator (Vitamin A): 1 capsule containing oil carrier and 50,000IU Vitamin A, within 48hs of birth

Placebo Comparator: 1 capsule containing oil carrier and 0IU Vitamin A, within 48hs of birth

Placebo Comparator: Placebo
Capsule containing oil vehicle withOUT Vitamin A (retinyl palmitate). Capsules are prepared by the manufacturer (Strides Arcolab Limited, India) and assigned blinded codes by World Health Organization officials.
Dietary Supplement: Vitamin A (retinyl palmitate).

Active Comparator (Vitamin A): 1 capsule containing oil carrier and 50,000IU Vitamin A, within 48hs of birth

Placebo Comparator: 1 capsule containing oil carrier and 0IU Vitamin A, within 48hs of birth


  Eligibility

Ages Eligible for Study:   up to 48 Hours
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • singleton birth,
  • birth weight ≥1,500g,
  • mother over 18 years willing to participate and residency within the study area.
  • Birth vaccinations and vitamin A supplement must be administered within 48 hours of birth.

Exclusion Criteria:

  • Infants having a congenital disease,
  • a serious infection at birth
  • an inability to feed (initially assessed by the lack of the suck reflex),
  • mothers who are seriously ill at time of enrolment (defined as bed bound for more than 24 hours),
  • mother participating in other studies,
  • mothers who are HIV positive.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01476358

Locations
Gambia
Medical Research Council, The Gambia Unit
Fajara, Gambia
Sponsors and Collaborators
London School of Hygiene and Tropical Medicine
World Health Organization
Investigators
Principal Investigator: Suzanna LR McDonald, BSc (Hons) MSc PhD London School of Hygiene and Tropical Medicine
  More Information

No publications provided by London School of Hygiene and Tropical Medicine

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: London School of Hygiene and Tropical Medicine
ClinicalTrials.gov Identifier: NCT01476358     History of Changes
Other Study ID Numbers: RPC389
Study First Received: November 9, 2011
Last Updated: November 12, 2012
Health Authority: Gambia: Department of State for Health and Social Welfare

Additional relevant MeSH terms:
Vitamin A Deficiency
Night Blindness
Avitaminosis
Deficiency Diseases
Malnutrition
Nutrition Disorders
Vision Disorders
Eye Diseases
Vitamin A
Vitamins
Retinol palmitate
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Anticarcinogenic Agents
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 20, 2014