HIV InfectionNCT01751646
Vitamin D Absorption in HIV Infected Young Adults Being Treated With Tenofovir Containing cART
A study testing Vitamin D3 50,000 IU in people with HIV Infection, run by University of North Carolina, Chapel Hill at 17 sites in 2 countries.
Trial summary
This is a 48 week randomized double-blind, placebo-controlled prospective cohort study of adolescents and young adults with HIV infection in the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) who are currently being treated with cART that includes tenofovir disoproxil fumarate (TDF) as one… Read more about this study
- Who is it for?
- Ages 16 to 24 years
- Conditions the study is for
- HIV Infection
- What is being tested?
- Vitamin D3 50,000 IU
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 214 participants
- Where
- 17 sitesin 2 countries
- Study dates
- Oct 2012to Jun 2016
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 24 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- To be considered eligible for enrollment, an individual must meet the criteria listed below at the time of randomization:
- NOTE: If the DXA scan is scheduled prior to randomization, all eligibility criteria must be met prior to performing the DXA scan.
- Age 16 years and 0 days to 24 years and 364 days;
- Behaviorally infected with HIV (e.g., sexual contact, injection drug use; not infected by perinatal transmission, blood transfusion, or at age younger than 9 years);
- HIV-1 infection as documented in subject's medical record by at least one of the following criteria:
- reactive HIV screening test result with an antibody based FDA-licensed assay followed by a positive supplemental assay (e.g., HIV-1 Western Blot, HIV-1 Indirect Immunofluorescence, Antibody Differentiation Assay (Multispot)); or
Show all 15Show fewer
- positive HIV-1 DNA polymerase chain reaction (PCR) assay; or
- plasma HIV-1 quantitative RNA assay >1,000 copies/mL; or
- positive plasma HIV-1 RNA qualitative assay
- Subjects must have at least one documented HIV viral load that is below 200 copies/mL collected following initiation of TDF containing cART and greater than 90 days prior to randomization; no HIV viral load above 200 copies/mL if measured within the 90 days prior to randomization; and an HIV viral load obtained at screening that is below 200 copies/mL.
- Currently being treated for at least 180 days by the time of randomization with a TDF containing cART with at least 2 other FDA approved ARVs (NOTE: This may include a TDF-containing fixed drug combination medication);
- Negative serum hepatitis B surface antigen (HBsAg) at screening or by history within 4 weeks prior to screening (see section 7.1.3);
- Willingness and ability to remain on the same cART regimen for the duration of study participation;
- Willingness and ability to participate in the study, follow all study procedures for the duration of study participation, and provide written informed consent or assent with parental permission, if applicable; and
- For females of child-bearing potential, agreement to use a minimum of one proven-effective method of birth control and willingness to postpone pregnancy for the duration of study participation (see section 5.3.2 for permitted hormonal contraceptives)
Who cannot join
- To be considered eligible for enrollment, an individual must not meet any of the criteria listed below at the time of randomization:
- NOTE: If the DXA scan is scheduled prior to randomization, all eligibility criteria must be met prior to performing the DXA scan.
- Prior hypersensitivity to vitamin D;
- History of sarcoidosis, arteriosclerosis, renal stones, glomerulonephritis, interstitial kidney disease, nephrotic syndrome, hypercalcemia, osteoporosis and/or other bone diseases, clinical diagnosis of hypoparathyroidism or hyperparathyroidism;
- Lactation or pregnancy currently or within the past 24 weeks;
- Chemotherapy or radiation therapy for malignancy within the past 12 months;
Show all 14Show fewer
- Known presence of GI disease that, in the opinion of the clinician, would interfere with study agent administration or absorption (e.g. Crohn's, Colitis);
- For subjects ≥ 18 years, confirmed creatinine clearance < 70 ml/min (estimated glomerular filtration rate (GFR) from SCr using Cockcroft and Gault (CG) equation) and for subjects <18 years, confirmed creatinine clearance < 70ml/min/1.73m2 (estimated GFR from SCr using Schwartz formula (see section 3.5). (Estimated GFR may be calculated using the formulae programmed on the ATN website);
- SCa > Upper Limit Normal (ULN) for local laboratory values (see section 7.1.3);
- Active Grade 3 or higher clinical or laboratory toxicity except atazanavir (ATV) associated indirect hyperbilirubinemia (see section 9.5.2.2);
- Weight is > 350 pounds (lbs) or 159 kilograms (kgs);
- Positive hepatitis C antibody by history or at screening (see section 7.1.3); and
- Use of any medications as specified in sections 5.3.1, 5.3.3 and 5.4.
- Females Only: Use of certain hormonal contraceptives as specified in the protocol.
Trial locations and contacts
17 sites in 2 countries.
17 sites in 2 countries
United States16 sites
Johns Hopkins University - NICHD Westat Site
Baltimore, Maryland, 21287
Johns Hopkins University
Baltimore, Maryland, 21287
Fenway Institute
Boston, Massachusetts, 02215
Stroger Hospital and the CORE Center
Chicago, Illinois, 60612
Wayne State University
Detroit, Michigan, 48201
Children's Diagnostic and Treatment Center - NICHD Westat Site
Fort Lauderdale, Florida, 33316
Baylor College of Medicine
Houston, Texas, 77030
Children's Hopsital of Los Angeles
Los Angeles, California, 90027
University of Southern California - NICHD Westat Site
Los Angeles, California, 90033
St. Jude Childrens Research Hospital
Memphis, Tennessee, 38105
University of Miami School of Medicine
Miami, Florida, 33101
Tulane Medical Center
New Orleans, Louisiana, 70112
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
University of South Florida
Tampa, Florida, 33606
Montefiore Medical Center
The Bronx, New York, 10467
Childrens National Medical Center
Washington D.C., District of Columbia, 20010
Puerto Rico1 site
San Juan City Hospital (Puerto Rico) - NICHD Westat Site
San Juan, 00936-5067
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled Trial of the Safety and Effectiveness of Vitamin D3 50,000 IU Every 4 Weeks to Increase Bone Mineral Density and Decrease Tenofovir-Induced Hyperparathyroidism in Youth With HIV Infection Being Treated With Tenofovir-Containing Combination Antiretroviral Therapy (cART)
This is a 48 week randomized double-blind, placebo-controlled prospective cohort study of adolescents and young adults with HIV infection in the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) who are currently being treated with cART that includes tenofovir disoproxil fumarate (TDF) as one component of the regimen that includes at least three Food and Drug Administration (FDA)-approved antiretroviral (ARV) drugs for at least 180 days.
Read the detailed description
This is a 48 week randomized double-blind, placebo-controlled prospective cohort study of adolescents and young adults with HIV infection in the ATN who are currently being treated with cART that includes TDF as one component of the regimen that includes at least three Food and Drug Administration (FDA)-approved ARVs for at least 180 days. Subjects must have at least one documented viral load that is below 200 copies/mL that is collected following initiation of TDF containing cART and greater than 90 days prior to randomization; no viral load above 200 copies/mL if measured within the 90 days prior to randomization; and an HIV viral load obtained at screening that is below 200 copies/mL.
Treatment assignments will be balanced by subject sex at birth, age (<20 years vs. >=20 years), and race (African American vs. other). Enrolled subjects will be randomized to receive vitamin D3 50000 IU or matching placebo, given orally every four weeks by DOT. In addition to the randomized study agent, all subjects will receive a MVI to be taken orally once daily. This "standard" MVI will contain ingredients not to exceed 600 IU of vitamin D3 and 200 mg Ca.
Dual energy x-ray absorptiometry (DXA) measurement of bone mineral content (BMC)/bone mineral density (BMD) of whole body, spine, and hip, will be performed at baseline and study weeks 24 and 48. Blood and urine sampling to assess the Ca-phosphorous (PO4) axis, parathyroid hormone (PTH)-FGF23-vitamin D signaling, bone turnover, and renal glomerular and tubular function will occur at baseline and study weeks 12, 24, and 48. Blood samples to measure Gluc homeostasis will be drawn at baseline and week 48, and will be run by batch analysis.
Safety, measured by serum calcium (SCa) and serum creatinine (SCr), will be monitored by subject's record review at study sites since these labs will generally be measured as a part of routine clinical care. The Adolescent Medicine Trials Network for HIV/AIDS Interventions 109 (ATN 109) study will use the SCa and SCr values obtained within 10 weeks at the time of the visit beginning at the baseline visit. If these evaluations were not performed within the prior 10 weeks they will be drawn at the time of each visit. Viral load and cluster of differentiation 4 (CD4) cell count results will be recorded for this study, ATN 109, at screening, baseline and study weeks 12, 24, 48, and Post-Week 48 provided the evaluations were done within the protocol specified timeframe. If the evaluations were not performed within the protocol specified timeframes they will be drawn at the time of the visit.
- Conditions
- HIV Infection
- Being tested
- Vitamin D3 50,000 IU, Vitamin D3 placebo
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin D3 50,000 IUDietary supplement
Also called Vitamin D3
Group A: Vitamin D3 50,000 IU orally every four weeks by DOT
Vitamin D3 placeboDietary supplement
Also called Placebo
Group B: Vitamin D3 placebo orally every four weeks by DOT
| Study group | Role | What they receive |
|---|---|---|
| Group A: Vitamin D3 50,000 IU | Experimental | Subjects randomized to Group A will receive Vitamin D3 50,000 IU orally every four weeks by directly observed therapy (DOT). In addition all subjects receive a multivitamin (MVI) that contains ingredients not to exceed 600 IU of vitamin D3 and 200 mg of Calcium (Ca). Subjects will self-administer one MVI tablet orally once daily. Receives: Dietary Supplement: Vitamin D3 50,000 IU |
| Group B: Vitamin D3 placebo | Placebo comparator | Subjects randomized to Group B will receive Vitamin D3 placebo orally every four weeks by DOT. In addition all subjects receive a MVI that contains ingredients not to exceed 600 IU of vitamin D3 and 200 mg of Ca. Subjects will self-administer one MVI tablet orally once daily. Receives: Dietary Supplement: Vitamin D3 placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change From Baseline to Week 48 in Dual Energy X-ray Absorptiometry (DXA)-Measured BMD at the Spine for the Randomized Study Groups
Percent change from baseline to week (wk) 48 in DXA-measured BMD at the spine for the randomized study groups.
Lumbar spine BMD (L1 - L4) (g/cm2) change from Baseline to wk 48 visit.
Measured: Baseline and wk 48
Secondary outcomes (71)
Percent Change From Baseline to Week 24 of BMC of Whole Body for the Randomized Study Groups
Measured: Baseline and week 24
Percent Change From Baseline to Week 48 of BMC of Whole Body for the Randomized Study Groups
Measured: Baseline and week 48
Percent Change From Baseline to Week 24 of Lumbar Spine (L1-L4) BMD for the Randomized Study Groups
Measured: Baseline and week 24
Change From Baseline to Week 24 of Lumbar Spine (L1-L4) BMD Z-score for the Randomized Study Groups
The Z-score is the standard deviation around mean bone mineral density in the lumbar spine, adjusted for sex, age, and race/ethnicity. An average Z-score of zero would be expected to be seen in healthy populations. A negative Z-score indicates lower than average bone mineral density. Low bone mineral density is a frequent finding in HIV-infected individuals, including adolescents and young adults.
Measured: Baseline and week 24
Change From Baseline to Week 48 of Lumbar Spine (L1-L4) BMD Z-score for the Randomized Study Groups
The Z-score is the standard deviation around mean bone mineral density in the lumbar spine, adjusted for sex, age, and race/ethnicity. An average Z-score of zero would be expected to be seen in healthy populations. A negative Z-score indicates lower than average bone mineral density. Low bone mineral density is a frequent finding in HIV-infected individuals, including adolescents and young adults.
Measured: Baseline and week 48
Percent Change From Baseline to Week 24 of Femoral Neck BMD for the Randomized Study Groups
Measured: Baseline and week 24
Percent Change From Baseline to Week 48 of Femoral Neck BMD for the Randomized Study Groups
Measured: Baseline and week 48
Change From Baseline to Week 24 of Femoral Neck BMD Z-score for the Randomized Study Groups
The Z-score is the standard deviation around mean bone mineral density in the femoral neck, adjusted for sex, age, and race/ethnicity. An average Z-score of zero would be expected to be seen in healthy populations. A negative Z-score indicates lower than average bone mineral density. Low bone mineral density is a frequent finding in HIV-infected individuals, including adolescents and young adults.
Measured: Baseline and week 24
Change From Baseline to Week 48 of Femoral Neck BMD Z-score for the Randomized Study Groups
The Z-score is the standard deviation around mean bone mineral density in the femoral neck, adjusted for sex, age, and race/ethnicity. An average Z-score of zero would be expected to be seen in healthy populations. A negative Z-score indicates lower than average bone mineral density. Low bone mineral density is a frequent finding in HIV-infected individuals, including adolescents and young adults.
Measured: Baseline and week 48
Percent Change From Baseline to Week 24 of Total Hip BMD for the Randomized Study Groups
Measured: Baseline and week 24
Percent Change From Baseline to Week 48 of Total Hip BMD for the Randomized Study Groups
Measured: Baseline and week 48
Change From Baseline to Week 24 of Total Hip BMD Z-score for the Randomized Study Groups
The Z-score is the standard deviation around mean bone mineral density in the total hip, adjusted for sex, age, and race/ethnicity. An average Z-score of zero would be expected to be seen in healthy populations. A negative Z-score indicates lower than average bone mineral density. Low bone mineral density is a frequent finding in HIV-infected individuals, including adolescents and young adults.
Measured: Baseline and week 24
Change From Baseline to Week 48 of Total Hip BMD Z-score for the Randomized Study Groups
The Z-score is the standard deviation around mean bone mineral density in the total hip, adjusted for sex, age, and race/ethnicity. An average Z-score of zero would be expected to be seen in healthy populations. A negative Z-score indicates lower than average bone mineral density. Low bone mineral density is a frequent finding in HIV-infected individuals, including adolescents and young adults.
Measured: Baseline and week 48
Change in SCr From Baseline to Week 12.
To assess renal glomerular safety by measuring change in SCr from baseline to week 12 by randomized study group;
Measured: Baseline and week 12
Change in SCr From Baseline to Week 24.
To assess renal glomerular safety by measuring change in SCr from baseline to week 24 by randomized study group;
Measured: Baseline and week 24
Change in SCr From Baseline to Week 48.
To assess renal glomerular safety by measuring change in SCr from baseline to week 48 by randomized study group;
Measured: Baseline and week 48
Change From Baseline to Week 48 in Glucose Homeostasis (Fasting Insulin)
Measured: Baseline and 48 weeks
Change From Baseline to Week 48 in Glucose Homeostasis (Fasting Glucose)
Measured: Baseline and week 48
Change From Baseline to Week 48 in Glucose Homeostasis (Homeostasis Model Assessment of Insulin Resistance (HOMA-IR))
HOMA-IR is calculated as fasting glucose (mg/dL) X fasting glucose (uIU/mL) / 405. An increase in HOMA-IR means that an individual has become more resistant (less sensitive) to the effects of insulin and thus would be a negative outcome. A reduction in HOMA-IR means that an individual has become more sensitive to the effects of insulin and would be considered a positive outcome.There are no set minimum or maximum scores for HOMA-IR, since it is based on measurements of insulin and glucose, the assays for which may vary. Several studies suggest a cut-off of >2 for any insulin resistance, but "normal" values appear to vary greatly by population (https://www.mdcalc.com/homa-ir-homeostatic-model-assessment-insulin-resistance).
Measured: Baseline and week 48
Change From Baseline to Week 12 in Serum Calcium (SCa)
Measured: Baseline and wk 12
Change From Baseline to Week 24 in Serum Calcium (SCa)
Measured: 24 weeks
Change From Baseline to Week 48 in Serum Calcium (SCa)
Measured: Baseline and wk 48
Change From Baseline to Week 12 in CTX
Measured: Baseline and week 12
Change From Baseline to Week 24 in CTX
Measured: Baseline and week 24
Change From Baseline to Week 48 in CTX
Measured: Baseline and week 48
Change From Baseline to Week 12 in OC
Measured: Baseline and week 12
Change From Baseline to Week 24 in OC
Measured: Baseline and week 24
Change From Baseline to Week 48 in OC
Measured: Baseline and wk 48
Change From Baseline to Week 12 in BAP
Measured: Baseline and wk 12
Change From Baseline to Week 24 in BAP
Measured: Baseline and wk 24
Change From Baseline to Week 48 in BAP
Measured: Baseline and wk 48
Change From Baseline to Week 12 in FGF23
Measured: Baseline and wk 12
Change From Baseline to Week 24 in FGF23
Measured: Baseline and wk 24
Change From Baseline to Week 48 in FGF23
Measured: Baseline and wk 48
Change From Baseline to Week 12 in PTH
Measured: Baseline and wk 12
Change From Baseline to Week 24 in PTH
Measured: Baseline and wk 24
Change From Baseline to Week 48 in PTH
Measured: Baseline and wk 48
Change From Baseline to Week 12 in Actual Free 1,25-OHD
Vitamin D serum concentration (1,25 (OH)DTotal) (pmol/L) multiplied by F times 1,000, where F is defined as F = 1/(1 + Kd * [VDBP] + Ka *[albumin]) where the binding constant for VDBP = Kd = 4.2 x 107 M-1, and for albumin is Ka = 5.4 x 104 M-1 and the concentrations of VDBP and albumin are in moles/L
Measured: Baseline and wk 12
Change From Baseline to Week 24 in Actual Free 1,25-OHD
Vitamin D serum concentration (1,25 (OH)DTotal) (pmol/L) multiplied by F times 1,000, where F is defined as F = 1/(1 + Kd * [VDBP] + Ka *[albumin]) where the binding constant for VDBP = Kd = 4.2 x 107 M-1, and for albumin is Ka = 5.4 x 104 M-1 and the concentrations of VDBP and albumin are in moles/L
Measured: Baseline and wk 24
Change From Baseline to Week 48 in Actual Free 1,25-OHD
Vitamin D serum concentration (1,25 (OH)DTotal) (pmol/L) multiplied by F times 1,000, where F is defined as F = 1/(1 + Kd * [VDBP] + Ka *[albumin]) where the binding constant for VDBP = Kd = 4.2 x 107 M-1, and for albumin is Ka = 5.4 x 104 M-1 and the concentrations of VDBP and albumin are in moles/L
Measured: Baseline and wk 48
Change From Baseline to Week 12 in 1,25-OHD
Measured: Baseline and wk 12
Change From Baseline to Week 24 in 1,25-OHD
Measured: Baseline and wk 24
Change From Baseline to Week 48 in 1,25-OHD
Measured: Baseline and wk 48
Change From Baseline to Week 12 in 25-OHD
Measured: Baseline and wk 12
Change From Baseline to Week 24 in 25-OHD
Measured: Baseline and wk 24
Change From Baseline to Week 48 in 25-OHD
Measured: Baseline and wk 48
Change From Baseline to Week 12 in TRP %
Measured: Baseline and wk 12
Change From Baseline to Week 24 in TRP %
Measured: Baseline and wk 24
Change From Baseline to Week 48 in TRP %
Measured: Baseline and wk 48
Change From Baseline to Week 12 in SPO4
Measured: Baseline and wk 12
Change From Baseline to Week 24 in SPO4
Measured: Baseline and wk 24
Change From Baseline to Week 48 in SPO4
Measured: Baseline and wk 48
Change From Baseline to Week 12 in UCa/Ucr
Measured: Baseline and wk 12
Change From Baseline to Week 24 in UCa/Ucr
Measured: Baseline and wk 24
Change From Baseline to Week 48 in UCa/Ucr
Measured: Baseline and wk 48
Change in Estimated GFR From Baseline to Week 12.
To assess renal glomerular safety by measuring change in estimated GFR from baseline to week 12 by randomized study group.
eGFR calculated by the CKD-Epi equation for subjects >=18 years of age, and by bedside Schwartz formula for subjects <18 years of age
Measured: Baseline and wk 12
Change in Estimated GFR From Baseline to Week 24.
To assess renal glomerular safety by measuring change in estimated GFR from baseline to week 24 by randomized study group;
Measured: Baseline and wk 24
Change in Estimated GFR From Baseline to Week 48.
To assess renal glomerular safety by measuring change in estimated GFR from baseline to week 48 by randomized study group;
Measured: Baseline and wk 48
Change in UGluc From Baseline to Week 48
To assess renal tubular function by measuring change in urine glucose (UGluc) by randomized study group;
Measured: Baseline and wk 48
Change in URBP/UCr Ratio From Baseline to Week 48
To assess renal tubular function by measuring change in urine retinol binding protein to urine creatinine (URBP/UCr) ratio by randomized study group;
Measured: Baseline and wk 48
Change in UB2MG From Baseline to Week 48
To assess renal tubular function by measuring change in urine beta-2 microglobulin (UB2MG) by randomized study group;
Measured: Baseline and wk 48
Change in UProt/ UCr Ratio From Baseline to Week 48
To assess renal tubular function by measuring change in urinary protein to creatinine ratio by randomized study group;
Measured: Baseline and wk 48
25-OHD Serum Concentration by Randomized Study Group at Week 12
Measured: Week 12
25-OHD Serum Concentration by Randomized Study Group at Week 24
Measured: Week 24
25-OHD Serum Concentration by Randomized Study Group at Week 48
Measured: Week 48
Effect of Concurrent Treatment With Efavirenz on 25-OHD Serum Concentration: Concentration at Baseline by Efavirenz Use
Mean Vitamin D serum concentration (25-(OH)D) Total) in those with efavirenz use vs. those without efavirenz use
Measured: Baseline
Effect of Concurrent Treatment With Efavirenz on 25-OHD Serum Concentration: Concentration at Week 48 by Efavirenz Use
Mean Vitamin D serum concentration (25-(OH)D) Total) in those with efavirenz use vs. those without efavirenz use
Measured: Week 48
Effect of Concurrent Treatment With Efavirenz on 25-OHD Serum Concentration: Change in Concentration From Baseline to Week 48 by Efavirenz Use
Mean Vitamin D serum concentration (25-(OH)D) Total) in those with efavirenz use vs. those without efavirenz use
Measured: Baseline and wk 48
Effect of Concurrent Treatment With Ritonavir on 25-OHD Serum Concentration: Concentration at Baseline by Ritonavir Use
Mean Vitamin D serum concentration (25-(OH)D) Total) in those with ritonavir use vs. those without ritonavir use
Measured: Baseline
Effect of Concurrent Treatment With Ritonavir on 25-OHD Serum Concentration: Concentration at Week 48 by Ritonavir Use
Mean Vitamin D serum concentration (25-(OH)D) Total) in those with ritonavir use vs. those without ritonavir use
Measured: Week 48
Effect of Concurrent Treatment With Ritonavir on 25-OHD Serum Concentration: Change in Concentration From Baseline to Week 48 by Ritonavir Use
Mean Vitamin D serum concentration (25-(OH)D) Total) in those with ritonavir use vs. those without ritonavir use
Measured: Baseline and wk 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2012 (estimated)
- Study startOct 2012
- Primary completionJun 2016
- Study completionJun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 214 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute on Drug Abuse (NIDA), National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- Peter Havens, MD, Study chair, MACC Fund Research Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01751646
- Sponsor's protocol ID
- ATN 109 Version 2.0
- Status last verified
- Nov 2018
- First submitted
- 14 Dec 2012
- Last updated
- 27 Mar 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Havens PL, Stephensen CB, Van Loan MD, Schuster GU, Woodhouse LR, Flynn PM, Gordon CM, Pan CG, Rutledge B, Harris DR, Price G, Baker A, Meyer WA 3rd, Wilson CM, Hazra R, Kapogiannis BG, Mulligan K; Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) 109 Study Team. Vitamin D3 Supplementation Increases Spine Bone Mineral Density in Adolescents and Young Adults With Human Immunodeficiency Virus Infection Being Treated With Tenofovir Disoproxil Fumarate: A Randomized, Placebo-Controlled Trial. Clin Infect Dis. 2018 Jan 6;66(2):220-228. doi: 10.1093/cid/cix753.
PubMed 29020329Havens PL, Long D, Schuster GU, Gordon CM, Price G, Wilson CM, Kapogiannis BG, Mulligan K, Stephensen CB; Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) 117 and 109 study teams. Tenofovir disoproxil fumarate appears to disrupt the relationship of vitamin D and parathyroid hormone. Antivir Ther. 2018;23(7):623-628. doi: 10.3851/IMP3269. Epub 2018 Sep 27.
PubMed 30260797
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled Trial of the Safety and Effectiveness of Vitamin D3 50,000 IU Every 4 Weeks to Increase Bone Mineral Density and Decrease Tenofovir-Induced Hyperparathyroidism in Youth With HIV Infection Being Treated With Tenofovir-Containing Combination Antiretroviral Therapy (cART)
- ClinicalTrials.gov ID
- NCT01751646
- Acronym / sponsor ID
- ATN 109 Version 2.0
- Conditions
- HIV Infection
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 214 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute on Drug Abuse (NIDA), National Institute of Mental Health (NIMH)
- Study start
- Oct 2012
- Primary completion
- Jun 2016 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 18 Dec 2012 (estimated)
- Results
- Posted 11 Mar 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a 48 week randomized double-blind, placebo-controlled prospective cohort study of adolescents and young adults with HIV infection in the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) who are currently being treated with cART that includes tenofovir disoproxil fumarate (TDF) as one component of the regimen that includes at least three Food and Drug Administration (FDA)-approved antiretroviral (ARV) drugs for at least 180 days.
Detailed description
This is a 48 week randomized double-blind, placebo-controlled prospective cohort study of adolescents and young adults with HIV infection in the ATN who are currently being treated with cART that includes TDF as one component of the regimen that includes at least three Food and Drug Administration (FDA)-approved ARVs for at least 180 days. Subjects must have at least one documented viral load that is below 200 copies/mL that is collected following initiation of TDF containing cART and greater than 90 days prior to randomization; no viral load above 200 copies/mL if measured within the 90 days prior to randomization; and an HIV viral load obtained at screening that is below 200 copies/mL.
Treatment assignments will be balanced by subject sex at birth, age (<20 years vs. >=20 years), and race (African American vs. other). Enrolled subjects will be randomized to receive vitamin D3 50000 IU or matching placebo, given orally every four weeks by DOT. In addition to the randomized study agent, all subjects will receive a MVI to be taken orally once daily. This "standard" MVI will contain ingredients not to exceed 600 IU of vitamin D3 and 200 mg Ca.
Dual energy x-ray absorptiometry (DXA) measurement of bone mineral content (BMC)/bone mineral density (BMD) of whole body, spine, and hip, will be performed at baseline and study weeks 24 and 48. Blood and urine sampling to assess the Ca-phosphorous (PO4) axis, parathyroid hormone (PTH)-FGF23-vitamin D signaling, bone turnover, and renal glomerular and tubular function will occur at baseline and study weeks 12, 24, and 48. Blood samples to measure Gluc homeostasis will be drawn at baseline and week 48, and will be run by batch analysis.
Safety, measured by serum calcium (SCa) and serum creatinine (SCr), will be monitored by subject's record review at study sites since these labs will generally be measured as a part of routine clinical care. The Adolescent Medicine Trials Network for HIV/AIDS Interventions 109 (ATN 109) study will use the SCa and SCr values obtained within 10 weeks at the time of the visit beginning at the baseline visit. If these evaluations were not performed within the prior 10 weeks they will be drawn at the time of each visit. Viral load and cluster of differentiation 4 (CD4) cell count results will be recorded for this study, ATN 109, at screening, baseline and study weeks 12, 24, 48, and Post-Week 48 provided the evaluations were done within the protocol specified timeframe. If the evaluations were not performed within the protocol specified timeframes they will be drawn at the time of the visit.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A: Vitamin D3 50,000 IU | Experimental | Dietary Supplement: Vitamin D3 50,000 IUSubjects randomized to Group A will receive Vitamin D3 50,000 IU orally every four weeks by directly observed therapy (DOT). In addition all subjects receive a multivitamin (MVI) that contains ingredients not to exceed 600 IU of vitamin D3 and 200 mg of Calcium (Ca). Subjects will self-administer one MVI tablet orally once daily. |
| Group B: Vitamin D3 placebo | Placebo comparator | Dietary Supplement: Vitamin D3 placeboSubjects randomized to Group B will receive Vitamin D3 placebo orally every four weeks by DOT. In addition all subjects receive a MVI that contains ingredients not to exceed 600 IU of vitamin D3 and 200 mg of Ca. Subjects will self-administer one MVI tablet orally once daily. |
Who may qualify
- Ages
- 16 to 24 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (15 listed)
- To be considered eligible for enrollment, an individual must meet the criteria listed below at the time of randomization:
- NOTE: If the DXA scan is scheduled prior to randomization, all eligibility criteria must be met prior to performing the DXA scan.
- Age 16 years and 0 days to 24 years and 364 days;
- Behaviorally infected with HIV (e.g., sexual contact, injection drug use; not infected by perinatal transmission, blood transfusion, or at age younger than 9 years);
- HIV-1 infection as documented in subject's medical record by at least one of the following criteria:
Key exclusion criteria (14 listed)
- To be considered eligible for enrollment, an individual must not meet any of the criteria listed below at the time of randomization:
- NOTE: If the DXA scan is scheduled prior to randomization, all eligibility criteria must be met prior to performing the DXA scan.
- Prior hypersensitivity to vitamin D;
- History of sarcoidosis, arteriosclerosis, renal stones, glomerulonephritis, interstitial kidney disease, nephrotic syndrome, hypercalcemia, osteoporosis and/or other bone diseases, clinical diagnosis of hypoparathyroidism or hyperparathyroidism;
- Lactation or pregnancy currently or within the past 24 weeks;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vitamin D3 50,000 IUAlso: Vitamin D3Group A: Vitamin D3 50,000 IU orally every four weeks by DOT | Dietary supplement | Group A: Vitamin D3 50,000 IU |
| Vitamin D3 placeboAlso: PlaceboGroup B: Vitamin D3 placebo orally every four weeks by DOT | Dietary supplement | Group B: Vitamin D3 placebo |
Primary outcome
Percent Change From Baseline to Week 48 in Dual Energy X-ray Absorptiometry (DXA)-Measured BMD at the Spine for the Randomized Study Groups
Time frame: Baseline and wk 48
Percent change from baseline to week (wk) 48 in DXA-measured BMD at the spine for the randomized study groups. Lumbar spine BMD (L1 - L4) (g/cm2) change from Baseline to wk 48 visit.
71 secondary outcomes
Percent Change From Baseline to Week 24 of BMC of Whole Body for the Randomized Study Groups
Time frame: Baseline and week 24
Percent Change From Baseline to Week 48 of BMC of Whole Body for the Randomized Study Groups
Time frame: Baseline and week 48
Percent Change From Baseline to Week 24 of Lumbar Spine (L1-L4) BMD for the Randomized Study Groups
Time frame: Baseline and week 24
Change From Baseline to Week 24 of Lumbar Spine (L1-L4) BMD Z-score for the Randomized Study Groups
Time frame: Baseline and week 24
Change From Baseline to Week 48 of Lumbar Spine (L1-L4) BMD Z-score for the Randomized Study Groups
Time frame: Baseline and week 48
Percent Change From Baseline to Week 24 of Femoral Neck BMD for the Randomized Study Groups
Time frame: Baseline and week 24
Percent Change From Baseline to Week 48 of Femoral Neck BMD for the Randomized Study Groups
Time frame: Baseline and week 48
Change From Baseline to Week 24 of Femoral Neck BMD Z-score for the Randomized Study Groups
Time frame: Baseline and week 24
Change From Baseline to Week 48 of Femoral Neck BMD Z-score for the Randomized Study Groups
Time frame: Baseline and week 48
Percent Change From Baseline to Week 24 of Total Hip BMD for the Randomized Study Groups
Time frame: Baseline and week 24
Percent Change From Baseline to Week 48 of Total Hip BMD for the Randomized Study Groups
Time frame: Baseline and week 48
Change From Baseline to Week 24 of Total Hip BMD Z-score for the Randomized Study Groups
Time frame: Baseline and week 24
Change From Baseline to Week 48 of Total Hip BMD Z-score for the Randomized Study Groups
Time frame: Baseline and week 48
Change in SCr From Baseline to Week 12.
Time frame: Baseline and week 12
Change in SCr From Baseline to Week 24.
Time frame: Baseline and week 24
Change in SCr From Baseline to Week 48.
Time frame: Baseline and week 48
Change From Baseline to Week 48 in Glucose Homeostasis (Fasting Insulin)
Time frame: Baseline and 48 weeks
Change From Baseline to Week 48 in Glucose Homeostasis (Fasting Glucose)
Time frame: Baseline and week 48
Change From Baseline to Week 48 in Glucose Homeostasis (Homeostasis Model Assessment of Insulin Resistance (HOMA-IR))
Time frame: Baseline and week 48
Change From Baseline to Week 12 in Serum Calcium (SCa)
Time frame: Baseline and wk 12
Change From Baseline to Week 24 in Serum Calcium (SCa)
Time frame: 24 weeks
Change From Baseline to Week 48 in Serum Calcium (SCa)
Time frame: Baseline and wk 48
Change From Baseline to Week 12 in CTX
Time frame: Baseline and week 12
Change From Baseline to Week 24 in CTX
Time frame: Baseline and week 24
Change From Baseline to Week 48 in CTX
Time frame: Baseline and week 48
Change From Baseline to Week 12 in OC
Time frame: Baseline and week 12
Change From Baseline to Week 24 in OC
Time frame: Baseline and week 24
Change From Baseline to Week 48 in OC
Time frame: Baseline and wk 48
Change From Baseline to Week 12 in BAP
Time frame: Baseline and wk 12
Change From Baseline to Week 24 in BAP
Time frame: Baseline and wk 24
Change From Baseline to Week 48 in BAP
Time frame: Baseline and wk 48
Change From Baseline to Week 12 in FGF23
Time frame: Baseline and wk 12
Change From Baseline to Week 24 in FGF23
Time frame: Baseline and wk 24
Change From Baseline to Week 48 in FGF23
Time frame: Baseline and wk 48
Change From Baseline to Week 12 in PTH
Time frame: Baseline and wk 12
Change From Baseline to Week 24 in PTH
Time frame: Baseline and wk 24
Change From Baseline to Week 48 in PTH
Time frame: Baseline and wk 48
Change From Baseline to Week 12 in Actual Free 1,25-OHD
Time frame: Baseline and wk 12
Change From Baseline to Week 24 in Actual Free 1,25-OHD
Time frame: Baseline and wk 24
Change From Baseline to Week 48 in Actual Free 1,25-OHD
Time frame: Baseline and wk 48
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 29020329Havens PL, Stephensen CB, Van Loan MD, Schuster GU, Woodhouse LR, Flynn PM, Gordon CM, Pan CG, Rutledge B, Harris DR, Price G, Baker A, Meyer WA 3rd, Wilson CM, Hazra R, Kapogiannis BG, Mulligan K; Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) 109 Study Team. Vitamin D3 Supplementation Increases Spine Bone Mineral Density in Adolescents and Young Adults With Human Immunodeficiency Virus Infection Being Treated With Tenofovir Disoproxil Fumarate: A Randomized, Placebo-Controlled Trial. Clin Infect Dis. 2018 Jan 6;66(2):220-228. doi: 10.1093/cid/cix753.
- Derived from this study: PubMed 30260797Havens PL, Long D, Schuster GU, Gordon CM, Price G, Wilson CM, Kapogiannis BG, Mulligan K, Stephensen CB; Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) 117 and 109 study teams. Tenofovir disoproxil fumarate appears to disrupt the relationship of vitamin D and parathyroid hormone. Antivir Ther. 2018;23(7):623-628. doi: 10.3851/IMP3269. Epub 2018 Sep 27.
- ATN websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter Havens, MD study chair
MACC Fund Research Center
17 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Vitamin D3 50,000 IU in people with HIV Infection, run by University of North Carolina, Chapel Hill at 17 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Mar 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change From Baseline to Week 48 in Dual Energy X-ray Absorptiometry (DXA)-Measured BMD at the Spine for the Randomized Study Groups (time frame: Baseline and wk 48). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01751646, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2019.