Clinical trial NCT01656070: Vitamin D Supplementation in HIV-infected Youth
Official title: Vitamin D Status and T Cell Phenotype in HIV-infected Youth Supplemented With Cholecalciferol: a Randomized Clinical Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Disease
Vitamin D Deficiency
Hypovitaminosis D
Hyperparathyroidism
Keywords: HIV
children
adolescents
Vitamin D
immunity
T cell phenotype
Lead sponsor: University of Milan
Sponsor class: OTHER
First posted: 2012-08-02
Enrollment: 50
Sex: ALL
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Along with its effects on bone metabolism, vitamin D is an important modulator of the immune system. Experimental studies have shown that the active metabolite of vitamin D \[1,25(OH)2D\] is able to skew the T cell compartment into a more anti-inflammatory state, with inhibition of Th1 and Th17 cells and promotion of Th2 and T regulatory subsets.

In the context of HIV infection, in which Th1 subpopulations are devoted to inhibit viral replication, any alteration of the Th1/Th2 balance would be of concern.

The aim of this Randomized Controlled Trial is to test wether oral supplementation with cholecalciferol could be able: 1) to improve vitamin D status and, 2) to play an immunomodulatory role, in vertically HIV-infected children and young adults with hypovitaminosis D.

Detailed description: There is increasing evidence that hypovitaminosis D is common in the general population.

Low dietary intake of vitamin D and reduced exposure to sunlight are probably the major risk factors. A high prevalence of hypovitaminosis D has been described in HIV-infected adults, and children. HIV infection itself and antiretroviral (ARV) treatment may be responsible for alteration of vitamin D metabolism. For instance, studies have shown a significant decrease in serum 25-hydroxyvitamin-D \[25(OH)D\] concentration in adults receiving non-nucleoside reverse transcriptase inhibitors (NNRTIs). Whatever the cause(s) of hypovitaminosis D, because of the importance of vitamin D in bone health, randomized controlled trials (RCT) have been performed to test whether vitamin D supplementation can improve vitamin D status and bone mineral metabolism in HIV-infected children and adolescents.

Along with its effects on bone metabolism, vitamin D is an important modulator of the immune system. The vitamin D receptor (VDR) is found in high concentrations in activated T lymphocytes, in small amounts in monocyte/macrophage cells while B lymphocytes do not contain detectable amounts of VDR.

Experimental studies have shown that the active di-hydroxylated metabolite of vitamin D \[1,25(OH)2D\] is able to skew the T cell compartment into a more anti-inflammatory state, with inhibition of Th1 and Th17 cells and promotion of Th2 and T regulatory (Treg) subsets.

In the context of HIV infection, in which Th1 subpopulations are devoted to inhibit viral replication, 16 any alteration of the Th1/Th2 balance would be of concern.

Although all the biological effects of vitamin D are mediated by the 1,25(OH)2D, it is the 25(OH)D to be routinely quantified because of its longer half-life.17 However, HIV-infected subjects may have a defective 1α-hydroxylation of 25(OH)D. Thus, it is important to evaluate the effects of vitamin D supplementation both in terms of 25(OH)D and 1,25(OH)2D responses.

This repeated-measures parallel-group RCT is aimed to test wether a 12-month oral supplementation with cholecalciferol (vitamin D3) is able: 1) to increase serum 25(OH)D and 1,25(OH)2D levels and, 2) to affect T-cell phenotype in vertically HIV-infected children and young adults with hypovitaminosis D and stable HIV-disease.

Main outcome: to determine the frequency of hypovitaminosis D at 12-month of follow-up among subjects supplemented with oral cholecalciferol versus subjects receiving placebo.

Secondary outcome: to investigate correlations - if any - between serum vitamin D concentration and markers of immune activation (i.e. Th1-, Th2-, Th17- and Treg-lymphocytes count, T-lymphocyte VDR expression)

Eligibility criteria: Inclusion Criteria:

* Vertically acquired HIV infection
* age \< 30 years
* serum 25(OH)D concentration \< 30 ng/mL
* signed written informed consent

Exclusion Criteria:

* hyperparathyroidism, as detected by an intact serum parathyroid hormone (PTH) ≥ 65 pg/mL
* Black ethnic group
* any supplementation with vitamin D in the previous 12 months
* use of any treatment known to alter vitamin D status in the previous 6 months (excluding ARV)
* any concomitant severe illness.

Primary outcomes:
measure: frequency of Hypovitaminosis D [serum 25(OH)D < 30 ng/mL] in the Vitamin D receiving group vs placebo group
timeFrame: 12 months
Secondary outcomes:
measure: Effect of oral cholecalciferol supplementation on T cell phenotype in vertically HIV-infected youth with stable HIV diseases
timeFrame: 12 months
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Department of Paediatrics - L. Sacco Hospital
Study officials:
affiliation: Department of Paediatrics, L. Sacco Hospital, University of Milan, Milan, Italy
name: Gian Vincenzo Zuccotti, Professor
role: PRINCIPAL_INVESTIGATOR
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