Vitamin A DeficiencyPhase 2NNVASNCT01476358
Effect of Vitamin A Supplementation on Immune Responses in Human Neonates
A Phase 2 study testing Vitamin A (retinyl palmitate). in people with Vitamin A Deficiency, run by London School of Hygiene and Tropical Medicine at 1 site in The Gambia.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 5 to 48 hoursHealthy volunteers can take part
- Conditions the study is for
- Vitamin A Deficiency
- What is being tested?
- Vitamin A (retinyl palmitate).
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 200 participants
- Where
- 1 siteThe Gambia
- Study dates
- Nov 2011to Jun 2013
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 48 hours
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized Controlled Trial in Human Neonates to Determine the Effect of Vitamin A Supplementation on Immune Responses
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.
- Conditions
- Vitamin A Deficiency
- Being tested
- Vitamin A (retinyl palmitate).
- Medical subject headings
- Vitamin A Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin A (retinyl palmitate).Dietary supplement
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
| Study group | Role | What they receive |
|---|---|---|
| Vitamin A | Active comparator | 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. Receives: Dietary Supplement: Vitamin A (retinyl palmitate). |
| Placebo | Placebo comparator | 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. Receives: Dietary Supplement: Vitamin A (retinyl palmitate). |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of circulating Tregs expressing gut homing receptors in infant participants.
Measured: 17 week post-supplementation
Secondary outcomes (3)
Difference in Thymus size in infant participants
Assessed by ultrasonic analysis.
Measured: 1, 6, 12 and 17 weeks
Difference in B cell immune responses after routine vaccination in infant participants
Assessed as an increase in B cell numbers and activation status.
Measured: 6 and 17 weeks
Improved mucosal barrier function in infant participants
Assessed by quantifying bacterial translocation into the blood.
Measured: 6 and 17 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2011 (estimated)
- Study startNov 2011
- Primary completionJun 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Vitamin A DeficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- London School of Hygiene and Tropical Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- World Health Organization
- Responsible party
- Sponsor
- Investigators
- Suzanna LR McDonald, BSc (Hons) MSc PhD, Principal investigator, London School of Hygiene and Tropical Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01476358
- Sponsor's protocol ID
- RPC389
- Acronym
- NNVAS
- Status last verified
- Nov 2012
- First submitted
- 9 Nov 2011
- Last updated
- 14 Nov 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
McDonald SL, Savy M, Fulford AJ, Kendall L, Flanagan KL, Prentice AM. A double blind randomized controlled trial in neonates to determine the effect of vitamin A supplementation on immune responses: The Gambia protocol. BMC Pediatr. 2014 Apr 4;14:92. doi: 10.1186/1471-2431-14-92.
PubMed 24708735
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Trial in Human Neonates to Determine the Effect of Vitamin A Supplementation on Immune Responses
- ClinicalTrials.gov ID
- NCT01476358
- Acronym / sponsor ID
- NNVAS / RPC389
- Conditions
- Vitamin A Deficiency
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- London School of Hygiene and Tropical MedicineUniversity, hospital or other
- Collaborators
- World Health Organization
- Study start
- Nov 2011
- Primary completion
- Jun 2013 (estimated)
- First posted
- 22 Nov 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vitamin A | Active comparator | Dietary Supplement: Vitamin A (retinyl palmitate).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. |
| Placebo | Placebo comparator | Dietary Supplement: Vitamin A (retinyl palmitate).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. |
Who may qualify
- Ages
- 5 to 48 hours
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (6 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | Dietary supplement | Placebo, Vitamin A |
Primary outcome
Frequency of circulating Tregs expressing gut homing receptors in infant participants.
Time frame: 17 week post-supplementation
3 secondary outcomes
Difference in Thymus size in infant participants
Time frame: 1, 6, 12 and 17 weeks
Difference in B cell immune responses after routine vaccination in infant participants
Time frame: 6 and 17 weeks
Improved mucosal barrier function in infant participants
Time frame: 6 and 17 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2012.
- Derived from this study: PubMed 24708735McDonald SL, Savy M, Fulford AJ, Kendall L, Flanagan KL, Prentice AM. A double blind randomized controlled trial in neonates to determine the effect of vitamin A supplementation on immune responses: The Gambia protocol. BMC Pediatr. 2014 Apr 4;14:92. doi: 10.1186/1471-2431-14-92.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Suzanna LR McDonald, BSc (Hons) MSc PhD principal investigator
London School of Hygiene and Tropical Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Vitamin A (retinyl palmitate). in people with Vitamin A Deficiency, run by London School of Hygiene and Tropical Medicine at 1 site in The Gambia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 14 Nov 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in The Gambia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Frequency of circulating Tregs expressing gut homing receptors in infant participants. (time frame: 17 week post-supplementation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01476358, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2012.