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High Dose Vitamin D and Calcium for Bone Health in Individuals Initiating HAART

This study has been completed.
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT01403051
First received: July 25, 2011
Last updated: December 22, 2015
Last verified: December 2015

July 25, 2011
December 22, 2015
September 2011
February 2013   (final data collection date for primary outcome measure)
The Percent Change From Baseline in Bone Mineral Density (BMD) at Total Hip [ Time Frame: Weeks 0 and 48 ] [ Designated as safety issue: No ]
The efficacy endpoint is the percent change from baseline to week 48 in bone mineral density (BMD) at total hip (as measured by DXA scan)
Efficacy endpoint [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
The efficacy endpoint is the percent change from baseline in bone mineral density (BMD) at total hip (as measured by DXA scan) at 48 weeks
Complete list of historical versions of study NCT01403051 on ClinicalTrials.gov Archive Site
  • The Percent Change From Baseline in Bone Mineral Density (BMD) at Spine [ Time Frame: Weeks 0 and 48 ] [ Designated as safety issue: No ]
    The percent change from baseline to week 48 in bone mineral density (BMD) at spine as measured by DXA scan
  • Number of Participants With Primary Adverse Events [ Time Frame: From first study treatment to week 48 ] [ Designated as safety issue: Yes ]
    Primary adverse events include all SAEs defined according to ICH guidelines and targeted protocol events, which include all diagnoses of hypercalcemia, hypophoatemia, and nephrolithiasis as well as signs and symptoms grade 2 or higher that may be associated with hypercalcemia and all laboratory toxicities grade 2 or higher defined by the 2004 DAIDS grading table
  • The Change in Total 25-OH Vitamin D Level From Baseline to Weeks 24 and 48 [ Time Frame: Weeks 0, 24, and 48 ] [ Designated as safety issue: No ]

    Changes in total 25-OH vitamin D from baseline to weeks 24 and 48 ( [week 24-baseline] and [week 48 - baseline], respectively).

    Total 25-OH vitamin D is the sum of vitamin 25-OH D2 and D3 levels. All 25-OH vitamin D2 or D3 values below the lower limit of 1.25 ng/mL were imputed to 0 ng/mL

  • The Changes From Baseline in IL-6 to Weeks 24 and 48 [ Time Frame: Weeks 0, 24 and 48 ] [ Designated as safety issue: No ]
    Interleukin 6 (IL-6) changes from baseline to weeks 24 and 48 ( [week 24-baseline] and [week 48 - baseline], respectively).
  • The Changes From Baseline in sCD14 to Weeks 24 and 48 [ Time Frame: Weeks 0, 24 and 48 ] [ Designated as safety issue: No ]
    Soluble cluster of differentiation 14 (sCD14) changes from baseline to weeks 24 and 48 ( [week 24-baseline] and [week 48 - baseline], respectively).
  • The Changes From Baseline in P1NP to Weeks 24 and 48 [ Time Frame: Weeks 0, 24 and 48 ] [ Designated as safety issue: No ]
    P1NP (marker of bone formation) changes from baseline to weeks 24 and 48 ( [week 24-baseline] and [week 48 - baseline], respectively).
  • The Changes From Baseline in CTX to Weeks 24 and 48 [ Time Frame: Weeks 0, 24 and 48 ] [ Designated as safety issue: No ]
    CTX (marker of bone resorption) changes from baseline to weeks 24 and 48 ( [week 24-baseline] and [week 48 - baseline], respectively).
  • The Changes From Baseline in HOMA-IR to Weeks 24 and 48 [ Time Frame: Weeks 0, 24 and 48 ] [ Designated as safety issue: No ]
    Homeostatic model assessment insulin resistance (HOMA-IR) changes from baseline to weeks 24 and 48 ( [week 24-baseline] and [week 48 - baseline], respectively).
  • The Changes From Baseline in Fasting Total Cholesterol to Weeks 24 and 48 [ Time Frame: Weeks 0, 24 and 48 ] [ Designated as safety issue: No ]
    Fasting total cholesterol changes from baseline to weeks 24 and 48 ( [week 24-baseline] and [week 48 - baseline], respectively).
  • The Changes From Baseline in Fasting LDL to Weeks 24 and 48 [ Time Frame: Weeks 0, 24 and 48 ] [ Designated as safety issue: No ]
    Fasting LDL cholesterol changes from baseline to weeks 24 and 48 ( [week 24-baseline] and [week 48 - baseline], respectively).
  • The Changes From Baseline in Urinary Phosphate Excretion to Weeks 24 and 48 [ Time Frame: Weeks 0, 24 and 48 ] [ Designated as safety issue: No ]

    Fractional excretion of phosphate changes from baseline to weeks 24 and 48 ( [week 24-baseline] and [week 48 - baseline], respectively).

    Fractional Excretion of Phosphate (in %) is defined as:

    [Urine Phosphate x Serum Creatinine] / [Urine Creatinine x Serum Phosphate] x 100%

  • The Changes From Baseline in CD4 to Weeks 4, 12, 24 and 48 [ Time Frame: Weeks 0, 4, 12, 24 and 48 ] [ Designated as safety issue: No ]
    Total CD4 count changes from baseline to weeks 4, 12, 24 and 48 [week 4/12/24/48 - baseline].
  • The Changes From Baseline in iPTH to Weeks 24 and 48 [ Time Frame: Weeks 0, 24 and 48 ] [ Designated as safety issue: No ]
    iPTH (Parathyroid Hormone, intact) changes from baseline to weeks 24 and 48 ( [week 24-baseline] and [week 48 - baseline], respectively).
  • The percent change from baseline in bone mineral density (BMD) at at spine (as measured by DXA scan) at 48 weeks [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • The change from baseline in vitamin D level at 24 and 48 weeks [ Time Frame: Weeks 24 and 48 ] [ Designated as safety issue: No ]
  • The changes from baseline in markers of bone turnover (osteocalcin, bone alkaline phosphatase, serum C-telopeptide, interleukin-6, and high-sensitivity C-reactive protein) at 24 and 48 weeks. [ Time Frame: Weeks 24 and 48 ] [ Designated as safety issue: No ]
  • The changes from baseline in markers of inflammation at 24 and 48 weeks [ Time Frame: Weeks 24 and 48 ] [ Designated as safety issue: No ]
  • The change from baseline in insulin sensitivity (HOMA-IR) at 24 and 48 weeks [ Time Frame: Weeks 24 and 48 ] [ Designated as safety issue: No ]
  • The changes from baseline in total cholesterol and LDL cholesterol at 24 and 48 weeks [ Time Frame: Weeks 24 and 48 ] [ Designated as safety issue: No ]
  • The change from baseline in urinary phosphate excretion at 12, 24, and 48 weeks [ Time Frame: Weeks 12, 24 and 48 ] [ Designated as safety issue: No ]
  • The change from baseline in CD4+ count at 4, 12, 24 and 48 weeks [ Time Frame: Weeks 4, 12, 24 and 48 ] [ Designated as safety issue: No ]
  • Occurrence of Grade ≥ 3 adverse events and selected Grade ≥ 2 adverse events related to hypercalcemia [ Time Frame: Week 48 ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
High Dose Vitamin D and Calcium for Bone Health in Individuals Initiating HAART
A Prospective, Randomized, Double-Blind Phase II Trial of High-Dose Vitamin D and Calcium for Bone Health in HIV-Infected Individuals Initiating Highly Active Antiretroviral Therapy (HAART)
This study was done with people who were infected with HIV and needed to start treatment for their HIV disease. The purpose of this study is to see if taking vitamin D and calcium will help prevent the bone loss that sometimes happens when people start HIV treatment. For this study, the following HIV treatment (or HAART) were provided in the form of a single tablet that contains three different drugs: efavirenz/emtricitabine/tenofovir (EFV/FTC/TDF). These drugs are approved by the FDA to treat HIV infection. The HIV treatment provided is common for people who are taking HIV drugs for the first time. The risks seen with this HIV treatment are the same that you would encounter when taking these drugs outside of the study. The lists of risks of this HIV treatment are included in this document because the drugs are provided by the study, not because the drugs are being tested. The purpose of the study is only to look at the impact of high doses of vitamin D and calcium in preventing bone loss. There are no study objectives related to HIV treatment (EFV/FTC/TDF).
Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
HIV-1 Infection
  • Drug: EFV/FTC/TDF
    FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla) 600 mg/200 mg/ 300 mg tablet taken orally once daily at bedtime on an empty stomach.
    Other Name: Atripla
  • Drug: Calcium Carbonate
    Calcium carbonate 500 mg tablet taken orally twice daily with food for 48 weeks.
  • Drug: Vitamin D3
    One Vitamin D3 4000 IU capsule taken orally once daily with food for 48 weeks.
  • Drug: Placebo for calcium carbonate
    A placebo for calcium carbonate twice daily taken orally as one x 0 mg tablets with food for 48 weeks
  • Drug: Placebo for vitamin D3
    A placebo for vitamin D3 once daily taken orally as one capsule with food for 48 weeks.
  • Experimental: Arm A: EFV/FTC/TDF plus vitamin D3 and calcium carbonate
    Participants were administered FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla), calcium carbonate and vitamin D3 4000 IU.
    Interventions:
    • Drug: EFV/FTC/TDF
    • Drug: Calcium Carbonate
    • Drug: Vitamin D3
  • Experimental: Arm B: EFV/FTC/TDF plus vitamin D placebo and calcium placebo
    Participants were administered FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla), a placebo for calcium carbonate, and a placebo for vitamin D3.
    Interventions:
    • Drug: EFV/FTC/TDF
    • Drug: Placebo for calcium carbonate
    • Drug: Placebo for vitamin D3
Overton ET, Chan ES, Brown TT, Tebas P, McComsey GA, Melbourne KM, Napoli A, Hardin WR, Ribaudo HJ, Yin MT. Vitamin D and Calcium Attenuate Bone Loss With Antiretroviral Therapy Initiation: A Randomized Trial. Ann Intern Med. 2015 Jun 16;162(12):815-24. doi: 10.7326/M14-1409.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
167
February 2013
February 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • HIV-1 infection
  • No evidence of any exclusionary resistance mutations based on results from any genotype assay from any laboratory that has a CLIA (Clinical Laboratory Improvement Amendments) certification or its equivalent. Results must be available from testing any time in the past or must be obtained prior to entry and reviewed by the site investigator.
  • ARV drug-naïve (<=10 days of ART at any time prior to entry) and no ARV drugs taken within the past 30 days.
  • CD4+ cell count of any value obtained within 90 days prior to study entry at any laboratory that has a CLIA certification or its equivalent.
  • HIV-1 RNA >1000 copies/mL obtained within 90 days prior to study entry at any laboratory that has a CLIA certification or its equivalent.
  • Certain laboratory values obtained within 30 days prior to entry (as indicated in section 4.1.6 of the protocol.
  • Serum calcium < 10.5 mg/dL within 30 days prior to entry.
  • For women of reproductive potential, negative serum or urine pregnancy test within 48 hours prior to initiating study medications.
  • Subjects must refrain from participating in a conception process (i.e., active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization) and if participating in sexual activity that could lead to pregnancy, the subject/partner must use at least two of the reliable forms of contraceptive listed in section 4.1.9 of the protocol.
  • 25-OH vitamin D >=10 ng/mL and <75 ng/mL.
  • Ability and willingness of subject or legally authorized representative to provide informed consent.

Exclusion Criteria:

  • Current or prior use of bisphosphonate therapy.
  • Use of vitamin D supplements greater than 800 IU/day within 30 days prior to entry.
  • Use of calcium supplements greater than 500 mg/day within 30 days prior to entry.
  • Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulations.
  • Any oral, intravenous, or inhaled steroids within the 30 days prior to enrollment(intranasal steroid use is allowed).
  • Use of androgenic hormones or growth hormones.
  • Receipt of systemic cytotoxic chemotherapy within 30 days prior to entry.
  • Pregnancy or currently breastfeeding.
  • Documentation of acute opportunistic infections within 30 days prior to entry.
  • Serious illness requiring systemic treatment and/or hospitalization until subject either completes therapy or is clinically stable on therapy, in the opinion of the site investigator, for at least 7 days prior to entry.
  • Weight >300 lbs (exceeds weight limit of DXA scanners).
  • History of nephrolithiasis (kidney stones).
  • History of osteoporosis (as documented by DXA scan) or fragility fracture.
  • Clinically active thyroid disease (use of thyroid hormone replacement therapy permitted but TSH must be in normal range).
  • Current imprisonment or involuntary incarceration in a medical facility for psychiatric illness.
  • Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
  • Any condition that, in the opinion of the site investigator, would compromise the subject's ability to participate in the study.
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Puerto Rico
 
NCT01403051
ACTG A5280, 1U01AI068636
Yes
Not Provided
Not Provided
AIDS Clinical Trials Group
AIDS Clinical Trials Group
National Institute of Allergy and Infectious Diseases (NIAID)
Study Chair: Edgar (Turner) Overton, MD Alabama Therapeutics CRS
Study Chair: Michael T Yin, MD, MS HIV Prevention & Treatment CRS
AIDS Clinical Trials Group
December 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP