High Dose Vitamin D and Calcium for Bone Health in Individuals Initiating HAART
- Conditions
- HIV-1 Infection
- Interventions
- Drug: EFV/FTC/TDFDrug: Placebo for calcium carbonateDrug: Calcium CarbonateDrug: Placebo for vitamin D3Drug: Vitamin D3
- Registration Number
- NCT01403051
- Lead Sponsor
- Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 167
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: EFV/FTC/TDF plus vitamin D3 and calcium carbonate EFV/FTC/TDF Participants were administered FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla), calcium carbonate and vitamin D3 4000 IU. Arm B: EFV/FTC/TDF plus vitamin D placebo and calcium placebo EFV/FTC/TDF Participants were administered FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla), a placebo for calcium carbonate, and a placebo for vitamin D3. Arm B: EFV/FTC/TDF plus vitamin D placebo and calcium placebo Placebo for calcium carbonate Participants were administered FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla), a placebo for calcium carbonate, and a placebo for vitamin D3. Arm B: EFV/FTC/TDF plus vitamin D placebo and calcium placebo Placebo for vitamin D3 Participants were administered FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla), a placebo for calcium carbonate, and a placebo for vitamin D3. Arm A: EFV/FTC/TDF plus vitamin D3 and calcium carbonate Calcium Carbonate Participants were administered FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla), calcium carbonate and vitamin D3 4000 IU. Arm A: EFV/FTC/TDF plus vitamin D3 and calcium carbonate Vitamin D3 Participants were administered FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla), calcium carbonate and vitamin D3 4000 IU.
- Primary Outcome Measures
Name Time Method The Percent Change From Baseline in Bone Mineral Density (BMD) at Total Hip Weeks 0 and 48 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)
- Secondary Outcome Measures
Name Time Method The Percent Change From Baseline in Bone Mineral Density (BMD) at Spine Weeks 0 and 48 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 From first study treatment to week 48 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 Weeks 0, 24, and 48 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/mLThe Changes From Baseline in IL-6 to Weeks 24 and 48 Weeks 0, 24 and 48 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 Weeks 0, 24 and 48 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 Weeks 0, 24 and 48 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 Weeks 0, 24 and 48 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 Weeks 0, 24 and 48 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 Weeks 0, 24 and 48 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 Weeks 0, 24 and 48 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 Weeks 0, 24 and 48 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 Weeks 0, 4, 12, 24 and 48 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 Weeks 0, 24 and 48 iPTH (Parathyroid Hormone, intact) changes from baseline to weeks 24 and 48 ( \[week 24-baseline\] and \[week 48 - baseline\], respectively).
Trial Locations
- Locations (39)
Hosp. of the Univ. of Pennsylvania CRS (6201)
🇺🇸Philadelphia, Pennsylvania, United States
Harbor-UCLA Med. Ctr. CRS (603)
🇺🇸Torrance, California, United States
Stanford CRS (501)
🇺🇸Palo Alto, California, United States
Unc Aids Crs (3201)
🇺🇸Chapel Hill, North Carolina, United States
The Miriam Hosp. ACTG CRS (2951)
🇺🇸Providence, Rhode Island, United States
Puerto Rico-AIDS CRS (5401)
🇵🇷San Juan, Puerto Rico
Alabama Therapeutics CRS (5801)
🇺🇸Birmingham, Alabama, United States
Bronx-Lebanon Hosp. Ctr. CRS (31469)
🇺🇸Bronx, New York, United States
Georgetown University CRS (GU CRS) (1008)
🇺🇸Washington, District of Columbia, United States
Regional Center for Infectious Disease, Wendover Medical Center CRS (3203)
🇺🇸Greensboro, North Carolina, United States
University of Colorado Hospital CRS (6101)
🇺🇸Aurora, Colorado, United States
AIDS Care CRS (1108)
🇺🇸Rochester, New York, United States
NY Univ. HIV/AIDS CRS (401)
🇺🇸New York, New York, United States
HIV Prevention & Treatment CRS (30329)
🇺🇸New York, New York, United States
New Jersey Medical School-Adult Clinical Research Ctr. CRS (31477)
🇺🇸Newark, New Jersey, United States
Washington University CRS (2101)
🇺🇸Saint Louis, Missouri, United States
Trinity Health and Wellness Center CRS (31443)
🇺🇸Dallas, Texas, United States
Usc Crs (1201)
🇺🇸Los Angeles, California, United States
Massachusetts General Hospital ACTG CRS (101)
🇺🇸Boston, Massachusetts, United States
Pittsburgh CRS (1001)
🇺🇸Pittsburgh, Pennsylvania, United States
UCLA CARE Center CRS (601)
🇺🇸Los Angeles, California, United States
Case CRS (2501)
🇺🇸Cleveland, Ohio, United States
MetroHealth CRS (2503)
🇺🇸Cleveland, Ohio, United States
The Ponce de Leon Ctr. CRS (5802)
🇺🇸Atlanta, Georgia, United States
Northwestern University CRS (2701)
🇺🇸Chicago, Illinois, United States
Rush University Medical Center (2702)
🇺🇸Chicago, Illinois, United States
Brigham and Women's Hosp. ACTG CRS (107)
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Med. Ctr., ACTG CRS (103)
🇺🇸Boston, Massachusetts, United States
IHV Baltimore Treatment CRS (4651)
🇺🇸Baltimore, Maryland, United States
Houston AIDS Research Team CRS (31473)
🇺🇸Houston, Texas, United States
Ucsd, Avrc Crs (701)
🇺🇸San Diego, California, United States
Univ. of Cincinnati CRS (2401)
🇺🇸Cincinnati, Ohio, United States
University of Washington AIDS CRS (1401)
🇺🇸Seattle, Washington, United States
Duke University Medical Center Adult CRS (1601)
🇺🇸Durham, North Carolina, United States
Ucsf Aids Crs (801)
🇺🇸San Francisco, California, United States
Vanderbilt Therapeutics CRS (3652)
🇺🇸Nashville, Tennessee, United States
University of Rochester ACTG CRS (1101)
🇺🇸Rochester, New York, United States
The Ohio State Univ. AIDS CRS (2301)
🇺🇸Columbus, Ohio, United States
Cornell CRS (7804)
🇺🇸New York, New York, United States