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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT01403051
First received: July 25, 2011
Last updated: March 18, 2014
Last verified: March 2014
  Purpose

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).


Condition Intervention Phase
HIV-1 Infection
Drug: EFV/FTC/TDF
Drug: Calcium Carbonate
Drug: Vitamin D3
Drug: Placebo for calcium carbonate
Drug: Placebo for vitamin D3
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by AIDS Clinical Trials Group:

Primary Outcome Measures:
  • 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)


Secondary Outcome Measures:
  • 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 From Baseline in 25-OH Vitamin D Level [ Time Frame: Weeks 0, 24, and 48 ] [ Designated as safety issue: No ]
    25-OH Vitamin D includes D2, D3, and total Vitamin D levels

  • The Changes From Baseline in Markers of Bone Turnover [ Time Frame: Weeks 0, 24 and 48 ] [ Designated as safety issue: No ]
    Markers of bone turnover includes procollagen type 1 N propeptide (P1NP) and serum C-telopeptide (CTX)

  • The Changes From Baseline in Markers of Inflammation [ Time Frame: Weeks 0, 24, and 48 ] [ Designated as safety issue: No ]
    Markers of inflammation include Interleukin-6 (IL6), Tumor Necrosis Factor-α Receptor 1 (TNFr1), Tumor Necrosis Factor-α Receptor 2 (TNFr2), and soluble CD14 (sCD14)

  • The Changes From Baseline in Fasting Lipids [ Time Frame: Weeks 0, 24, and 48 ] [ Designated as safety issue: No ]
    fasting lipids include fasting total cholesterol and fasting calculated LDL (low-density lipoprotein)

  • The Change From Baseline in Urinary Phosphate Excretion [ Time Frame: Weeks 0, 24, and 48 ] [ Designated as safety issue: No ]

    Urinary phosphate excretion is defined as:

    serum phosphate - (urine phosphate x serum creatinine / urine creatinine)


  • The Change From Baseline in CD4+ Count [ Time Frame: Weeks 0, 24, and 48 ] [ Designated as safety issue: No ]
  • The Change From Baseline in Intact Parathyroid Hormone (iPTH) Levels [ Time Frame: Weeks 0, 24, and 48 ] [ Designated as safety issue: No ]

Enrollment: 167
Study Start Date: September 2011
Study Completion Date: February 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.
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.
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: 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01403051

  Hide Study Locations
Locations
United States, Alabama
Alabama Therapeutics CRS (5801)
Birmingham, Alabama, United States, 35294
United States, California
UCLA CARE Center CRS (601)
Los Angeles, California, United States, 90095
Usc Crs (1201)
Los Angeles, California, United States, 90033
Stanford CRS (501)
Palo Alto, California, United States, 94304
Ucsd, Avrc Crs (701)
San Diego, California, United States, 92103
Ucsf Aids Crs (801)
San Francisco, California, United States, 94110
Harbor-UCLA Med. Ctr. CRS (603)
Torrance, California, United States, 90502
United States, Colorado
University of Colorado Hospital CRS (6101)
Aurora, Colorado, United States, 80045
United States, District of Columbia
Georgetown University CRS (GU CRS) (1008)
Washington, District of Columbia, United States, 20007
United States, Georgia
The Ponce de Leon Ctr. CRS (5802)
Atlanta, Georgia, United States, 30308
United States, Illinois
Rush University Medical Center (2702)
Chicago, Illinois, United States, 60612
Northwestern University CRS (2701)
Chicago, Illinois, United States, 60611
United States, Maryland
IHV Baltimore Treatment CRS (4651)
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Massachusetts General Hospital ACTG CRS (101)
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Med. Ctr., ACTG CRS (103)
Boston, Massachusetts, United States, 02215
Brigham and Women's Hosp. ACTG CRS (107)
Boston, Massachusetts, United States, 02115
United States, Missouri
Washington University CRS (2101)
St. Louis, Missouri, United States, 63110
United States, New Jersey
New Jersey Medical School-Adult Clinical Research Ctr. CRS (31477)
Newark, New Jersey, United States, 07103
United States, New York
Bronx-Lebanon Hosp. Ctr. CRS (31469)
Bronx, New York, United States, 10457
HIV Prevention & Treatment CRS (30329)
New York, New York, United States, 10032
Cornell CRS (7804)
New York, New York, United States, 10011
NY Univ. HIV/AIDS CRS (401)
New York, New York, United States, 10016
AIDS Care CRS (1108)
Rochester, New York, United States, 14642
University of Rochester ACTG CRS (1101)
Rochester, New York, United States, 14642
United States, North Carolina
Unc Aids Crs (3201)
Chapel Hill, North Carolina, United States, 27514
Duke University Medical Center Adult CRS (1601)
Durham, North Carolina, United States, 27710
Regional Center for Infectious Disease, Wendover Medical Center CRS (3203)
Greensboro, North Carolina, United States, 27401
United States, Ohio
Univ. of Cincinnati CRS (2401)
Cincinnati, Ohio, United States, 45267
Case CRS (2501)
Cleveland, Ohio, United States, 44106
MetroHealth CRS (2503)
Cleveland, Ohio, United States, 44109
The Ohio State Univ. AIDS CRS (2301)
Columbus, Ohio, United States, 43210
United States, Pennsylvania
Hosp. of the Univ. of Pennsylvania CRS (6201)
Philadelphia, Pennsylvania, United States, 19104
Pittsburgh CRS (1001)
Pittsburgh, Pennsylvania, United States, 15213
United States, Rhode Island
The Miriam Hosp. ACTG CRS (2951)
Providence, Rhode Island, United States, 02906
United States, Tennessee
Vanderbilt Therapeutics CRS (3652)
Nashville, Tennessee, United States, 37232
United States, Texas
Trinity Health and Wellness Center CRS (31443)
Dallas, Texas, United States, 75208
Houston AIDS Research Team CRS (31473)
Houston, Texas, United States, 77030
United States, Washington
University of Washington AIDS CRS (1401)
Seattle, Washington, United States, 98104
Puerto Rico
Puerto Rico-AIDS CRS (5401)
San Juan, Puerto Rico, 00935
Sponsors and Collaborators
AIDS Clinical Trials Group
Investigators
Study Chair: Edgar (Turner) Overton, MD Alabama Therapeutics CRS
Study Chair: Michael T Yin, MD, MS HIV Prevention & Treatment CRS
  More Information

No publications provided

Responsible Party: AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT01403051     History of Changes
Other Study ID Numbers: ACTG A5280, 1U01AI068636
Study First Received: July 25, 2011
Results First Received: February 5, 2014
Last Updated: March 18, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Calcium Carbonate
Calcium, Dietary
Cholecalciferol
Efavirenz, emtricitabine, tenofovir disoproxil fumarate drug combination
Ergocalciferols
Tenofovir
Tenofovir disoproxil
Vitamin D
Vitamins
Antacids
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Bone Density Conservation Agents
Enzyme Inhibitors
Growth Substances
Micronutrients
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014