Vitamin D Supplementation in HIV-infected Youth

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gian Vincenzo Zuccotti, University of Milan
ClinicalTrials.gov Identifier:
NCT01656070
First received: July 31, 2012
Last updated: August 1, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention Phase
HIV Disease
Vitamin D Deficiency
Hypovitaminosis D
Hyperparathyroidism
Drug: oral cholecalciferol 1000000 UI (vitamin D3)
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Vitamin D Status and T Cell Phenotype in HIV-infected Youth Supplemented With Cholecalciferol: a Randomized Clinical Trial.

Resource links provided by NLM:


Further study details as provided by University of Milan:

Primary Outcome Measures:
  • frequency of Hypovitaminosis D [serum 25(OH)D < 30 ng/mL] in the Vitamin D receiving group vs placebo group [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    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


Secondary Outcome Measures:
  • Effect of oral cholecalciferol supplementation on T cell phenotype in vertically HIV-infected youth with stable HIV diseases [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 50
Study Start Date: April 2011
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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

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

Ages Eligible for Study:   up to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01656070

Locations
Italy
Department of Paediatrics - L. Sacco Hospital
Milan, Italy, 20157
Sponsors and Collaborators
University of Milan
Investigators
Principal Investigator: Gian Vincenzo Zuccotti, Professor Department of Paediatrics, L. Sacco Hospital, University of Milan, Milan, Italy
  More Information

Publications:
Ryan P. Random allocation of treatments in blocks. Stata Journal;8:594, 2008

Responsible Party: Gian Vincenzo Zuccotti, Gian Vincenzo Zuccotti, Associate Professor of Pediatrics, Chief of Department of Pediatrics at L. Sacco Hospital, University of Milan
ClinicalTrials.gov Identifier: NCT01656070     History of Changes
Other Study ID Numbers: HLS02/2011-1.0-09-11-2010, 2011-000593-54
Study First Received: July 31, 2012
Last Updated: August 1, 2012
Health Authority: Italy: The Italian Medicines Agency

Keywords provided by University of Milan:
HIV
children
adolescents
Vitamin D
immunity
T cell phenotype

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Hyperparathyroidism
Rickets
Vitamin D Deficiency
Avitaminosis
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Parathyroid Diseases
Endocrine System Diseases
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Calcium Metabolism Disorders
Metabolic Diseases
Deficiency Diseases
Malnutrition
Nutrition Disorders
Cholecalciferol
Vitamin D
Ergocalciferols
Vitamins
Micronutrients

ClinicalTrials.gov processed this record on April 17, 2014