Vitamin D Supplementation in HIV-infected Youth

August 1, 2012 updated by: Gian Vincenzo Zuccotti, University of Milan

Vitamin D Status and T Cell Phenotype in HIV-infected Youth Supplemented With Cholecalciferol: a Randomized Clinical Trial.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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)

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Milan, Italy, 20157
        • Department of Paediatrics - L. Sacco Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 30 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Vitamin D

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.
Drug: oral cholecalciferol 1000000 UI (vitamin D3)
Other Names:
  • DIBASE - ABIOGEN PHARMA Spa
PLACEBO_COMPARATOR: placebo

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.
Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
frequency of Hypovitaminosis D [serum 25(OH)D < 30 ng/mL] in the Vitamin D receiving group vs placebo group
Time Frame: 12 months
Vertically HIV-infected patients aged <30 years and with serum 25(OH)D < 30 ng/mL were randomized into the vitamin D or placebo group. At baseline (0 months), 3, 6 and 9 months, the intervention group received orally 100000 IU of cholecalciferol. Serum 25(OH)D, 1,25(OH)2D, PTH and CD4+ T cells were assessed 3 months before baseline, at 0, 3, 6, 9 and 12 months, while Th1-, Th2-, Th17- and Treg-subsets and T-lymphocyte vitamin D receptor at 0, 3 and 12 months
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effect of oral cholecalciferol supplementation on T cell phenotype in vertically HIV-infected youth with stable HIV diseases
Time Frame: 12 months
Vertically HIV-infected patients aged <30 years and with serum 25(OH)D < 30 ng/mL were randomized into the vitamin D or placebo group. At baseline (0 months), 3, 6 and 9 months, the intervention group received orally 100000 IU of cholecalciferol. CD4+ T-cells were assessed 3 months before enrollment (-3 months), at baseline (0 months) and at each visit thereafter (3, 6, 9 and 12 months). T-lymphocyte VDR expression and Th1-, Th2-, Th17- and Treg-lymphocytes were measured at 0, 3 and 12 months.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Milan

Investigators

  • Principal Investigator: Gian Vincenzo Zuccotti, Professor, Department of Paediatrics, L. Sacco Hospital, University of Milan, Milan, Italy

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2011

Primary Completion (ACTUAL)

July 1, 2012

Study Completion (ACTUAL)

July 1, 2012

Study Registration Dates

First Submitted

July 31, 2012

First Submitted That Met QC Criteria

August 1, 2012

First Posted (ESTIMATE)

August 2, 2012

Study Record Updates

Last Update Posted (ESTIMATE)

August 2, 2012

Last Update Submitted That Met QC Criteria

August 1, 2012

Last Verified

August 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HLS02/2011-1.0-09-11-2010
  • 2011-000593-54 (EUDRACT_NUMBER)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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