Vitamin D Supplementation in HIV-infected Youth

University of Milan

Status and phase: Completed; Phase 2

Conditions: HIV Disease; Vitamin D Deficiency; Hyperparathyroidism; Hypovitaminosis D

Treatments: Drug: Placebo; Drug: oral cholecalciferol 1000000 UI (vitamin D3)

Study type: Interventional

Funder types: Other

Identifiers

NCT01656070

HLS02/2011-1.0-09-11-2010

2011-000593-54 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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)

Enrollment: 50 patients

Sex: All

Ages: Under 30 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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50 participants in 2 patient groups, including a placebo group

Vitamin D

Experimental group

Description:

oral cholecalciferol 1000000 UI (vitamin D3). At 0, 3, 6 and 9 months, the vitamin D group received orally 100000 IU of cholecalciferol suspended in 2 mL of olive oil in sealed plastic syringes labeled with the unique identification numbers.

Treatment:

Drug: oral cholecalciferol 1000000 UI (vitamin D3)

placebo

Placebo Comparator group

Description:

placebo At 0, 3, 6 and 9 months, the placebo group received 2 mL of olive oil, in sealed plastic syringes labeled with the unique identification numbers.

Treatment:

Drug: Placebo