Source: AGRICULTURAL RESEARCH SERVICE submitted to
RANDOMIZED, PLACEBO-CONTROLLED TRIAL OF THE SAFETY AND EFFECTIVENESS OF VITAMIN D SUPPLEMENT
Sponsoring Institution
Agricultural Research Service/USDA
Project Status
TERMINATED
Funding Source
Reporting Frequency
Annual
Accession No.
0412300
Grant No.
(N/A)
Project No.
5306-51530-018-10R
Proposal No.
(N/A)
Multistate No.
(N/A)
Program Code
(N/A)
Project Start Date
Oct 1, 2007
Project End Date
Feb 28, 2011
Grant Year
(N/A)
Project Director
STEPHENSEN C B
Recipient Organization
AGRICULTURAL RESEARCH SERVICE
800 BUCHANAN ST, RM 2020
BERKELEY,CA 94710-1105
Performing Department
(N/A)
Non Technical Summary
(N/A)
Animal Health Component
0%
Research Effort Categories
Basic
100%
Applied
0%
Developmental
0%
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
70260101010100%
Goals / Objectives
Our interest in this study stems from its use of vitamin D as an intervention to treat probable vitamin D insufficiency and deficiency in African American adolescents. This poor vitamin D status is hypothesized to be a principal contributor to altered calcium metabolism that is negatively affecting bone health in these subjects. In addition to poor vitamin D status, the chronic inflammation of HIV is also postulated to have a detrimental effect on bone turnover in these subjects. In addition, some subjects in the study will be taking an antriretroviral drug (Tenovovir) that appears to have a detrimental effect on vitamin D metabolism, replicating what is seen in non-HIV-infected subjects with impaired kidney function. Thus examination of the interaction of kidney function and inflammation on vitamin D homeostasis in subjects with vitamin D insufficiency is a useful model to predict how subjects with other chronic inflammatory conditions (e.g., metabolic syndrome, type II diabetes) may benefit from vitamin D supplementation. The principal goal of the study is to determine if vitamin D supplements to treat vitamin D deficiency or insufficiency decrease bone turnover associated with chronic inflammation and a drug regimen with toxicity for kidney tubular epithelial cells, where 25OH vitamin D is converted to its active metabolite, calcitriol, for regulation of calcium homeostasis. The subjects in the study are primarily African American adolescents and are at increased risk of vitamin D insufficiency or deficiency due to skin pigmentation, low milk intake, and (possibly) low sun exposure.
Project Methods
This is a multi-center study with the Aids Trial Network, a group Dr. Stephensen has worked with previously (when it was known as the REACH network). This is a randomized, placebo-controlled intervention with vitamin D to examine the impact of an ÿ¿adolescent friendlyÿ¿ vitamin D supplementation regimen (50,000 IU per month in a single dose) to improve vitamin D status. If successful, this might be a useful approach for subjects at high risk of vitamin D insufficiency or deficiency for whom daily supplements or increased dietary intake of vitamin D are not anticipated to be effective in improving vitamin D status. This study may thus be useful in planning population-based strategies for dealing with the high prevalence of vitamin D deficiency in the US population, particularly in African Americans. Documents Trust with University of Alabama (National Institute of Child Health and Human Development). Log 33840. Formerly 5306-51530-013-09R (10/09).

Progress 10/01/07 to 02/28/11

Outputs
Progress Report Objectives (from AD-416) Our interest in this study stems from its use of vitamin D as an intervention to treat probable vitamin D insufficiency and deficiency in African American adolescents. This poor vitamin D status is hypothesized to be a principal contributor to altered calcium metabolism that is negatively affecting bone health in these subjects. In addition to poor vitamin D status, the chronic inflammation of HIV is also postulated to have a detrimental effect on bone turnover in these subjects. In addition, some subjects in the study will be taking an antriretroviral drug (Tenovovir) that appears to have a detrimental effect on vitamin D metabolism, replicating what is seen in non-HIV-infected subjects with impaired kidney function. Thus examination of the interaction of kidney function and inflammation on vitamin D homeostasis in subjects with vitamin D insufficiency is a useful model to predict how subjects with other chronic inflammatory conditions (e.g., metabolic syndrome, type II diabetes) may benefit from vitamin D supplementation. The principal goal of the study is to determine if vitamin D supplements to treat vitamin D deficiency or insufficiency decrease bone turnover associated with chronic inflammation and a drug regimen with toxicity for kidney tubular epithelial cells, where 25OH vitamin D is converted to its active metabolite, calcitriol, for regulation of calcium homeostasis. The subjects in the study are primarily African American adolescents and are at increased risk of vitamin D insufficiency or deficiency due to skin pigmentation, low milk intake, and (possibly) low sun exposure. Approach (from AD-416) This is a multi-center study with the Aids Trial Network, a group the ARS scientist and principal investigator has worked with previously (when it was known as the REACH network). This is a randomized, placebo- controlled intervention with vitamin D to examine the impact of an �adolescent friendly� vitamin D supplementation regimen (50,000 IU per month in a single dose) to improve vitamin D status. If successful, this might be a useful approach for subjects at high risk of vitamin D insufficiency or deficiency for whom daily supplements or increased dietary intake of vitamin D are not anticipated to be effective in improving vitamin D status. This study may thus be useful in planning population-based strategies for dealing with the high prevalence of vitamin D deficiency in the US population, particularly in African Americans. Documents Trust with University of Alabama (National Institute of Child Health and Human Development). Log 33840. Formerly 5306-51530-013-09R (10/09). Enrollment and subject follow-up is complete. Laboratory analysis is now complete, data analysis is in progress and one manuscript has been submitted for publication. The principal objective of the study was to determine the effect of vitamin D supplementation on kidney function, using tubular reabsorption of phosphate as a marker (TRP), serum parathyroid hormone levels (PTH), and on bone metabolism, using serum levels of bone-specific alkaline phosphatase (BAP), and C-telopeptide (CTX) as markers, in HIV-infected youth receiving and not receiving tenofovir-containing antiretroviral therapy (TDF). This was a randomized, double blind, placebo-controlled multicenter trial. HIV-infected youth 18-24 years of age with relatively low plasma viral loads (<5,000 copies/mL), were enrolled based on stable treatment therapy containing TDF (N=118) or not containing TDF (noTDF; N=85). Subjects were randomized within those groups to Vitamin D3 50,000 IU (N=102) or placebo (PL; N=101) with dosing at 0, 4, and 8 weeks. Outcome measures included change in TRP, PTH, BAP, and CTX from baseline to week 12. Results of the trial will be reported upon acceptance of the manuscript by an appropriate journal.

Impacts
(N/A)

Publications


    Progress 10/01/09 to 09/30/10

    Outputs
    Progress Report Objectives (from AD-416) Our interest in this study stems from its use of vitamin D as an intervention to treat probable vitamin D insufficiency and deficiency in African American adolescents. This poor vitamin D status is hypothesized to be a principal contributor to altered calcium metabolism that is negatively affecting bone health in these subjects. In addition to poor vitamin D status, the chronic inflammation of HIV is also postulated to have a detrimental effect on bone turnover in these subjects. In addition, some subjects in the study will be taking an antriretroviral drug (Tenovovir) that appears to have a detrimental effect on vitamin D metabolism, replicating what is seen in non-HIV-infected subjects with impaired kidney function. Thus examination of the interaction of kidney function and inflammation on vitamin D homeostasis in subjects with vitamin D insufficiency is a useful model to predict how subjects with other chronic inflammatory conditions (e.g., metabolic syndrome, type II diabetes) may benefit from vitamin D supplementation. The principal goal of the study is to determine if vitamin D supplements to treat vitamin D deficiency or insufficiency decrease bone turnover associated with chronic inflammation and a drug regimen with toxicity for kidney tubular epithelial cells, where 25OH vitamin D is converted to its active metabolite, calcitriol, for regulation of calcium homeostasis. The subjects in the study are primarily African American adolescents and are at increased risk of vitamin D insufficiency or deficiency due to skin pigmentation, low milk intake, and (possibly) low sun exposure. Approach (from AD-416) This is a multi-center study with the Aids Trial Network, a group Dr. Stephensen has worked with previously (when it was known as the REACH network). This is a randomized, placebo-controlled intervention with vitamin D to examine the impact of an �adolescent friendly� vitamin D supplementation regimen (50,000 IU per month in a single dose) to improve vitamin D status. If successful, this might be a useful approach for subjects at high risk of vitamin D insufficiency or deficiency for whom daily supplements or increased dietary intake of vitamin D are not anticipated to be effective in improving vitamin D status. This study may thus be useful in planning population-based strategies for dealing with the high prevalence of vitamin D deficiency in the US population, particularly in African Americans. Documents Trust with University of Alabama (National Institute of Child Health and Human Development). Log 33840. Formerly 5306-51530-013-09R (10/09). There were a total of 203 participants. Laboratory analysis is now complete for 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D, serum calcium, urine calcium, serum parathyroid hormone, serum alkaline phosphatase, serum c-terminal peptide of collagen, serum creatinine, urine creatinine, urine beta-2 microglobulin.

    Impacts
    (N/A)

    Publications


      Progress 10/01/08 to 09/30/09

      Outputs
      Progress Report Objectives (from AD-416) Our interest in this study stems from its use of vitamin D as an intervention to treat probable vitamin D insufficiency and deficiency in African American adolescents. This poor vitamin D status is hypothesized to be a principal contributor to altered calcium metabolism that is negatively affecting bone health in these subjects. In addition to poor vitamin D status, the chronic inflammation of HIV is also postulated to have a detrimental effect on bone turnover in these subjects. In addition, some subjects in the study will be taking an antriretroviral drug (Tenovovir) that appears to have a detrimental effect on vitamin D metabolism, replicating what is seen in non-HIV-infected subjects with impaired kidney function. Thus examination of the interaction of kidney function and inflammation on vitamin D homeostasis in subjects with vitamin D insufficiency is a useful model to predict how subjects with other chronic inflammatory conditions (e.g., metabolic syndrome, type II diabetes) may benefit from vitamin D supplementation. The principal goal of the study is to determine if vitamin D supplements to treat vitamin D deficiency or insufficiency decrease bone turnover associated with chronic inflammation and a drug regimen with toxicity for kidney tubular epithelial cells, where 25OH vitamin D is converted to its active metabolite, calcitriol, for regulation of calcium homeostasis. The subjects in the study are primarily African American adolescents and are at increased risk of vitamin D insufficiency or deficiency due to skin pigmentation, low milk intake, and (possibly) low sun exposure. Approach (from AD-416) This is a multi-center study with the Aids Trial Network, a group Dr. Stephensen has worked with previously (when it was known as the REACH network). This is a randomized, placebo-controlled intervention with vitamin D to examine the impact of an �adolescent friendly� vitamin D supplementation regimen (50,000 IU per month in a single dose) to improve vitamin D status. If successful, this might be a useful approach for subjects at high risk of vitamin D insufficiency or deficiency for whom daily supplements or increased dietary intake of vitamin D are not anticipated to be effective in improving vitamin D status. This study may thus be useful in planning population-based strategies for dealing with the high prevalence of vitamin D deficiency in the US population, particularly in African Americans. Documents Trust with University of Alabama (National Institute of Child Health and Human Development). Log 33840. Significant Activities that Support Special Target Populations Investigators at the WHNRC continue to collaborate on the implementation of this study, which is still enrolling subjects at multiple clinic sites around the US. Samples are being shipped to the WHNRC for analysis of serum 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D, bone metabolism markers and markers of inflammation and calcium status.

      Impacts
      (N/A)

      Publications


        Progress 10/01/07 to 09/30/08

        Outputs
        Progress Report Objectives (from AD-416) Our interest in this study stems from its use of vitamin D as an intervention to treat probable vitamin D insufficiency and deficiency in African American adolescents. This poor vitamin D status is hypothesized to be a principal contributor to altered calcium metabolism that is negatively affecting bone health in these subjects. In addition to poor vitamin D status, the chronic inflammation of HIV is also postulated to have a detrimental effect on bone turnover in these subjects. In addition, some subjects in the study will be taking an antriretroviral drug (Tenovovir) that appears to have a detrimental effect on vitamin D metabolism, replicating what is seen in non-HIV-infected subjects with impaired kidney function. Thus examination of the interaction of kidney function and inflammation on vitamin D homeostasis in subjects with vitamin D insufficiency is a useful model to predict how subjects with other chronic inflammatory conditions (e.g., metabolic syndrome, type II diabetes) may benefit from vitamin D supplementation. The principal goal of the study is to determine if vitamin D supplements to treat vitamin D deficiency or insufficiency decrease bone turnover associated with chronic inflammation and a drug regimen with toxicity for kidney tubular epithelial cells, where 25OH vitamin D is converted to its active metabolite, calcitriol, for regulation of calcium homeostasis. The subjects in the study are primarily African American adolescents and are at increased risk of vitamin D insufficiency or deficiency due to skin pigmentation, low milk intake, and (possibly) low sun exposure. Approach (from AD-416) This is a multi-center study with the Aids Trial Network, a group Dr. Stephensen has worked with previously (when it was known as the REACH network). This is a randomized, placebo-controlled intervention with vitamin D to examine the impact of an �adolescent friendly� vitamin D supplementation regimen (50,000 IU per month in a single dose) to improve vitamin D status. If successful, this might be a useful approach for subjects at high risk of vitamin D insufficiency or deficiency for whom daily supplements or increased dietary intake of vitamin D are not anticipated to be effective in improving vitamin D status. This study may thus be useful in planning population-based strategies for dealing with the high prevalence of vitamin D deficiency in the US population, particularly in African Americans. Documents Trust with University of Alabama (National Institute of Child Health and Human Development). Log 33840. Significant Activities that Support Special Target Populations This is a multi-center study with the Aids Trial Network, a group Dr. Stephensen has worked with previously (when it was known as the REACH network). This is a randomized, placebo-controlled intervention with vitamin D to examine the impact of an �adolescent friendly� vitamin D supplementation regimen (50,000 IU per month in a single dose) to improve vitamin D status. If successful, this might be a useful approach for subjects at high risk of vitamin D insufficiency or deficiency for whom daily supplements or increased dietary intake of vitamin D are not anticipated to be effective in improving vitamin D status. This study may thus be useful in planning population-based strategies for dealing with the high prevalence of vitamin D deficiency in the US population, particularly in African Americans. NP107, Component 5, Health Promoting Properties of Plant and Animal Foods.

        Impacts
        (N/A)

        Publications