Clinical trial NCT01403051: High Dose Vitamin D and Calcium for Bone Health in Individuals Initiating HAART
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV-1 Infection
Lead sponsor: Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
Sponsor class: NETWORK
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2011-07-27
Enrollment: 167
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility 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.

Primary outcomes:
measure: The Percent Change From Baseline in Bone Mineral Density (BMD) at Total Hip
timeFrame: Weeks 0 and 48
Secondary outcomes:
measure: The Percent Change From Baseline in Bone Mineral Density (BMD) at Spine
timeFrame: Weeks 0 and 48
measure: Number of Participants With Primary Adverse Events
timeFrame: From first study treatment to week 48
measure: The Change in Total 25-OH Vitamin D Level From Baseline to Weeks 24 and 48
timeFrame: Weeks 0, 24, and 48
measure: The Changes From Baseline in IL-6 to Weeks 24 and 48
timeFrame: Weeks 0, 24 and 48
measure: The Changes From Baseline in sCD14 to Weeks 24 and 48
timeFrame: Weeks 0, 24 and 48
measure: The Changes From Baseline in P1NP to Weeks 24 and 48
timeFrame: Weeks 0, 24 and 48
measure: The Changes From Baseline in CTX to Weeks 24 and 48
timeFrame: Weeks 0, 24 and 48
measure: The Changes From Baseline in HOMA-IR to Weeks 24 and 48
timeFrame: Weeks 0, 24 and 48
measure: The Changes From Baseline in Fasting Total Cholesterol to Weeks 24 and 48
timeFrame: Weeks 0, 24 and 48
measure: The Changes From Baseline in Fasting LDL to Weeks 24 and 48
timeFrame: Weeks 0, 24 and 48
measure: The Changes From Baseline in Urinary Phosphate Excretion to Weeks 24 and 48
timeFrame: Weeks 0, 24 and 48
measure: The Changes From Baseline in CD4 to Weeks 4, 12, 24 and 48
timeFrame: Weeks 0, 4, 12, 24 and 48
measure: The Changes From Baseline in iPTH to Weeks 24 and 48
timeFrame: Weeks 0, 24 and 48
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Therapeutics CRS (5801)
state: Alabama
city: Los Angeles
country: United States
facility: Usc Crs (1201)
state: California
city: Los Angeles
country: United States
facility: UCLA CARE Center CRS (601)
state: California
city: Palo Alto
country: United States
facility: Stanford CRS (501)
state: California
city: San Diego
country: United States
facility: Ucsd, Avrc Crs (701)
state: California
city: San Francisco
country: United States
facility: Ucsf Aids Crs (801)
state: California
city: Torrance
country: United States
facility: Harbor-UCLA Med. Ctr. CRS (603)
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital CRS (6101)
state: Colorado
city: Washington
country: United States
facility: Georgetown University CRS (GU CRS) (1008)
state: District of Columbia
city: Atlanta
country: United States
facility: The Ponce de Leon Ctr. CRS (5802)
state: Georgia
city: Chicago
country: United States
facility: Northwestern University CRS (2701)
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center (2702)
state: Illinois
city: Baltimore
country: United States
facility: IHV Baltimore Treatment CRS (4651)
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital ACTG CRS (101)
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hosp. ACTG CRS (107)
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Med. Ctr., ACTG CRS (103)
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University CRS (2101)
state: Missouri
city: Newark
country: United States
facility: New Jersey Medical School-Adult Clinical Research Ctr. CRS (31477)
state: New Jersey
city: Bronx
country: United States
facility: Bronx-Lebanon Hosp. Ctr. CRS (31469)
state: New York
city: New York
country: United States
facility: Cornell CRS (7804)
state: New York
city: New York
country: United States
facility: NY Univ. HIV/AIDS CRS (401)
state: New York
city: New York
country: United States
facility: HIV Prevention & Treatment CRS (30329)
state: New York
city: Rochester
country: United States
facility: AIDS Care CRS (1108)
state: New York
city: Rochester
country: United States
facility: University of Rochester ACTG CRS (1101)
state: New York
city: Chapel Hill
country: United States
facility: Unc Aids Crs (3201)
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center Adult CRS (1601)
state: North Carolina
city: Greensboro
country: United States
facility: Regional Center for Infectious Disease, Wendover Medical Center CRS (3203)
state: North Carolina
city: Cincinnati
country: United States
facility: Univ. of Cincinnati CRS (2401)
state: Ohio
city: Cleveland
country: United States
facility: Case CRS (2501)
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth CRS (2503)
state: Ohio
city: Columbus
country: United States
facility: The Ohio State Univ. AIDS CRS (2301)
state: Ohio
city: Philadelphia
country: United States
facility: Hosp. of the Univ. of Pennsylvania CRS (6201)
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Pittsburgh CRS (1001)
state: Pennsylvania
city: Providence
country: United States
facility: The Miriam Hosp. ACTG CRS (2951)
state: Rhode Island
city: Nashville
country: United States
facility: Vanderbilt Therapeutics CRS (3652)
state: Tennessee
city: Dallas
country: United States
facility: Trinity Health and Wellness Center CRS (31443)
state: Texas
city: Houston
country: United States
facility: Houston AIDS Research Team CRS (31473)
state: Texas
city: Seattle
country: United States
facility: University of Washington AIDS CRS (1401)
state: Washington
city: San Juan
country: Puerto Rico
facility: Puerto Rico-AIDS CRS (5401)
Study officials:
affiliation: Alabama Therapeutics CRS
name: Edgar (Turner) Overton, MD
role: STUDY_CHAIR
affiliation: HIV Prevention & Treatment CRS
name: Michael T Yin, MD, MS
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.