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

NCT01403051 | Completed Phase 2 Results DMC

• 2 other identifiers: ACTG A52801U01AI068636
• Study Type: interventional
• Target: 167
• Locations: 2 countries
• Sites: 39

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).

Conditions

HIV-1 Infection

Outcome Measures

Primary Outcomes (1)

• The Percent Change From Baseline in Bone Mineral Density (BMD) at Total Hip

  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)

  Weeks 0 and 48

Secondary Outcomes (13)

• The Percent Change From Baseline in Bone Mineral Density (BMD) at Spine

  Weeks 0 and 48

• Number of Participants With Primary Adverse Events

  From first study treatment to week 48

• The Change in Total 25-OH Vitamin D Level From Baseline to Weeks 24 and 48

  Weeks 0, 24, and 48

• The Changes From Baseline in IL-6 to Weeks 24 and 48

  Weeks 0, 24 and 48

• The Changes From Baseline in sCD14 to Weeks 24 and 48

  Weeks 0, 24 and 48

Study Arms (2)

Arm A: EFV/FTC/TDF plus vitamin D3 and calcium carbonate

EXPERIMENTAL

Participants were administered FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla), calcium carbonate and vitamin D3 4000 IU.

Drug: EFV/FTC/TDF; Drug: Calcium Carbonate; Drug: Vitamin D3

Arm B: EFV/FTC/TDF plus vitamin D placebo and calcium placebo

EXPERIMENTAL

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; Drug: Placebo for calcium carbonate; Drug: Placebo for vitamin D3

Interventions

EFV/FTC/TDF DRUG

FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla) 600 mg/200 mg/ 300 mg tablet taken orally once daily at bedtime on an empty stomach.

Also known as: Atripla

Arm A: EFV/FTC/TDF plus vitamin D3 and calcium carbonate; Arm B: EFV/FTC/TDF plus vitamin D placebo and calcium placebo

Calcium Carbonate DRUG

Calcium carbonate 500 mg tablet taken orally twice daily with food for 48 weeks.

Arm A: EFV/FTC/TDF plus vitamin D3 and calcium carbonate

Vitamin D3 DRUG

One Vitamin D3 4000 IU capsule taken orally once daily with food for 48 weeks.

Arm A: EFV/FTC/TDF plus vitamin D3 and calcium carbonate

Placebo for calcium carbonate DRUG

A placebo for calcium carbonate twice daily taken orally as one x 0 mg tablets with food for 48 weeks

Arm B: EFV/FTC/TDF plus vitamin D placebo and calcium placebo

Placebo for vitamin D3 DRUG

A placebo for vitamin D3 once daily taken orally as one capsule with food for 48 weeks.

Arm B: EFV/FTC/TDF plus vitamin D placebo and calcium placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV-1 infection
• 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.
• OH vitamin D \>=10 ng/mL and \<75 ng/mL.
• Ability and willingness of subject or legally authorized representative to provide informed consent.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (39)

Alabama Therapeutics CRS (5801)

Birmingham, Alabama, 35294, United States

Location

Usc Crs (1201)

Los Angeles, California, 90033, United States

Location

UCLA CARE Center CRS (601)

Los Angeles, California, 90095, United States

Location

Stanford CRS (501)

Palo Alto, California, 94304, United States

Location

Ucsd, Avrc Crs (701)

San Diego, California, 92103, United States

Location

Ucsf Aids Crs (801)

San Francisco, California, 94110, United States

Location

Harbor-UCLA Med. Ctr. CRS (603)

Torrance, California, 90502, United States

Location

University of Colorado Hospital CRS (6101)

Aurora, Colorado, 80045, United States

Location

Georgetown University CRS (GU CRS) (1008)

Washington D.C., District of Columbia, 20007, United States

Location

The Ponce de Leon Ctr. CRS (5802)

Atlanta, Georgia, 30308, United States

Location

Northwestern University CRS (2701)

Chicago, Illinois, 60611, United States

Location

Rush University Medical Center (2702)

Chicago, Illinois, 60612, United States

Location

IHV Baltimore Treatment CRS (4651)

Baltimore, Maryland, 21201, United States

Location

Massachusetts General Hospital ACTG CRS (101)

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hosp. ACTG CRS (107)

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Med. Ctr., ACTG CRS (103)

Boston, Massachusetts, 02215, United States

Location

Washington University CRS (2101)

St Louis, Missouri, 63110, United States

Location

New Jersey Medical School-Adult Clinical Research Ctr. CRS (31477)

Newark, New Jersey, 07103, United States

Location

Cornell CRS (7804)

New York, New York, 10011, United States

Location

NY Univ. HIV/AIDS CRS (401)

New York, New York, 10016, United States

Location

HIV Prevention & Treatment CRS (30329)

New York, New York, 10032, United States

Location

AIDS Care CRS (1108)

Rochester, New York, 14642, United States

Location

University of Rochester ACTG CRS (1101)

Rochester, New York, 14642, United States

Location

Bronx-Lebanon Hosp. Ctr. CRS (31469)

The Bronx, New York, 10457, United States

Location

Unc Aids Crs (3201)

Chapel Hill, North Carolina, 27514, United States

Location

Duke University Medical Center Adult CRS (1601)

Durham, North Carolina, 27710, United States

Location

Regional Center for Infectious Disease, Wendover Medical Center CRS (3203)

Greensboro, North Carolina, 27401, United States

Location

Univ. of Cincinnati CRS (2401)

Cincinnati, Ohio, 45267, United States

Location

Case CRS (2501)

Cleveland, Ohio, 44106, United States

Location

MetroHealth CRS (2503)

Cleveland, Ohio, 44109, United States

Location

The Ohio State Univ. AIDS CRS (2301)

Columbus, Ohio, 43210, United States

Location

Hosp. of the Univ. of Pennsylvania CRS (6201)

Philadelphia, Pennsylvania, 19104, United States

Location

Pittsburgh CRS (1001)

Pittsburgh, Pennsylvania, 15213, United States

Location

The Miriam Hosp. ACTG CRS (2951)

Providence, Rhode Island, 02906, United States

Location

Vanderbilt Therapeutics CRS (3652)

Nashville, Tennessee, 37232, United States

Location

Trinity Health and Wellness Center CRS (31443)

Dallas, Texas, 75208, United States

Location

Houston AIDS Research Team CRS (31473)

Houston, Texas, 77030, United States

Location

University of Washington AIDS CRS (1401)

Seattle, Washington, 98104, United States

Location

Puerto Rico-AIDS CRS (5401)

San Juan, 00935, Puerto Rico

Location

Related Publications (3)

• Yin MT, Chan ES, Brown TT, Kinslow J, Martinson J, Landay A, Melbourne KM, Ribaudo HJ, Overton ET; A5280 Study Team. Vitamin D does not modulate immune-mediated bone loss during ART initiation. Antivir Ther. 2019;24(5):355-362. doi: 10.3851/IMP3316.

  PMID: 31085814 DERIVED

• Yin MT, Chan ES, Brown TT, Tebas P, McComsey GA, Melbourne KM, Napoli A, Hardin WR, Ribaudo HJ, Overton ET; A5280 Study Team. Racial differences in calculated bioavailable vitamin D with vitamin D/calcium supplementation. AIDS. 2017 Nov 13;31(17):2337-2344. doi: 10.1097/QAD.0000000000001621.

  PMID: 28832406 DERIVED

• 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.

  PMID: 26075752 DERIVED

MeSH Terms

Interventions

Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Calcium Carbonate; Cholecalciferol

Intervention Hierarchy (Ancestors)

Tenofovir; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Drug Combinations; Pharmaceutical Preparations; Calcium Compounds; Inorganic Chemicals; Carbonates; Carbonic Acid; Carbon Compounds, Inorganic; Minerals; Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Results Point of Contact

• Title: ACTG ClinicalTrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.

ACTGCT.Gov@s-3.com

(301) 628-3313

Study Officials

• Edgar (Turner) Overton, MD

  Alabama Therapeutics CRS

  STUDY CHAIR

• Michael T Yin, MD, MS

  HIV Prevention & Treatment CRS

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2011
• First Posted: July 27, 2011
• Study Start: September 1, 2011
• Primary Completion: February 1, 2013
• Study Completion: February 1, 2013
• Last Updated: October 12, 2018
• Results First Posted: March 19, 2014

Record last verified: 2018-09

Locations

US (38); PR (1)