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

HIV-1 Infection Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01403051
• Other study ID #: ACTG A5280
• Secondary ID: 1U01AI068636
• Status: Completed
• Phase: Phase 2
• Start date: September 2011
• Est. completion date: February 2013

Study information

• Verified date: September 2018
• Source: AIDS Clinical Trials Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 167
• Est. completion date: February 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• HIV-1 Infection

Intervention

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.
• Calcium Carbonate
Calcium carbonate 500 mg tablet taken orally twice daily with food for 48 weeks.
• Vitamin D3
One Vitamin D3 4000 IU capsule taken orally once daily with food for 48 weeks.
• Placebo for calcium carbonate
A placebo for calcium carbonate twice daily taken orally as one x 0 mg tablets with food for 48 weeks
• Placebo for vitamin D3
A placebo for vitamin D3 once daily taken orally as one capsule with food for 48 weeks.

Locations

Country	Name	City	State
Puerto Rico	Puerto Rico-AIDS CRS (5401)	San Juan
United States	The Ponce de Leon Ctr. CRS (5802)	Atlanta	Georgia
United States	University of Colorado Hospital CRS (6101)	Aurora	Colorado
United States	IHV Baltimore Treatment CRS (4651)	Baltimore	Maryland
United States	Alabama Therapeutics CRS (5801)	Birmingham	Alabama
United States	Beth Israel Deaconess Med. Ctr., ACTG CRS (103)	Boston	Massachusetts
United States	Brigham and Women's Hosp. ACTG CRS (107)	Boston	Massachusetts
United States	Massachusetts General Hospital ACTG CRS (101)	Boston	Massachusetts
United States	Bronx-Lebanon Hosp. Ctr. CRS (31469)	Bronx	New York
United States	Unc Aids Crs (3201)	Chapel Hill	North Carolina
United States	Northwestern University CRS (2701)	Chicago	Illinois
United States	Rush University Medical Center (2702)	Chicago	Illinois
United States	Univ. of Cincinnati CRS (2401)	Cincinnati	Ohio
United States	Case CRS (2501)	Cleveland	Ohio
United States	MetroHealth CRS (2503)	Cleveland	Ohio
United States	The Ohio State Univ. AIDS CRS (2301)	Columbus	Ohio
United States	Trinity Health and Wellness Center CRS (31443)	Dallas	Texas
United States	Duke University Medical Center Adult CRS (1601)	Durham	North Carolina
United States	Regional Center for Infectious Disease, Wendover Medical Center CRS (3203)	Greensboro	North Carolina
United States	Houston AIDS Research Team CRS (31473)	Houston	Texas
United States	UCLA CARE Center CRS (601)	Los Angeles	California
United States	Usc Crs (1201)	Los Angeles	California
United States	Vanderbilt Therapeutics CRS (3652)	Nashville	Tennessee
United States	Cornell CRS (7804)	New York	New York
United States	HIV Prevention & Treatment CRS (30329)	New York	New York
United States	NY Univ. HIV/AIDS CRS (401)	New York	New York
United States	New Jersey Medical School-Adult Clinical Research Ctr. CRS (31477)	Newark	New Jersey
United States	Stanford CRS (501)	Palo Alto	California
United States	Hosp. of the Univ. of Pennsylvania CRS (6201)	Philadelphia	Pennsylvania
United States	Pittsburgh CRS (1001)	Pittsburgh	Pennsylvania
United States	The Miriam Hosp. ACTG CRS (2951)	Providence	Rhode Island
United States	AIDS Care CRS (1108)	Rochester	New York
United States	University of Rochester ACTG CRS (1101)	Rochester	New York
United States	Washington University CRS (2101)	Saint Louis	Missouri
United States	Ucsd, Avrc Crs (701)	San Diego	California
United States	Ucsf Aids Crs (801)	San Francisco	California
United States	University of Washington AIDS CRS (1401)	Seattle	Washington
United States	Harbor-UCLA Med. Ctr. CRS (603)	Torrance	California
United States	Georgetown University CRS (GU CRS) (1008)	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
AIDS Clinical Trials Group	National Institute of Allergy and Infectious Diseases (NIAID)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	The Percent Change From Baseline in Bone Mineral Density (BMD) at Spine	The percent change from baseline to week 48 in bone mineral density (BMD) at spine as measured by DXA scan	Weeks 0 and 48
Secondary	Number of Participants With Primary Adverse Events	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	From first study treatment to week 48
Secondary	The Change in Total 25-OH Vitamin D Level From Baseline to Weeks 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/mL	Weeks 0, 24, and 48
Secondary	The Changes From Baseline in IL-6 to Weeks 24 and 48	Interleukin 6 (IL-6) changes from baseline to weeks 24 and 48 ( [week 24-baseline] and [week 48 - baseline], respectively).	Weeks 0, 24 and 48
Secondary	The Changes From Baseline in sCD14 to Weeks 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).	Weeks 0, 24 and 48
Secondary	The Changes From Baseline in P1NP to Weeks 24 and 48	P1NP (marker of bone formation) changes from baseline to weeks 24 and 48 ( [week 24-baseline] and [week 48 - baseline], respectively).	Weeks 0, 24 and 48
Secondary	The Changes From Baseline in CTX to Weeks 24 and 48	CTX (marker of bone resorption) changes from baseline to weeks 24 and 48 ( [week 24-baseline] and [week 48 - baseline], respectively).	Weeks 0, 24 and 48
Secondary	The Changes From Baseline in HOMA-IR to Weeks 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).	Weeks 0, 24 and 48
Secondary	The Changes From Baseline in Fasting Total Cholesterol to Weeks 24 and 48	Fasting total cholesterol changes from baseline to weeks 24 and 48 ( [week 24-baseline] and [week 48 - baseline], respectively).	Weeks 0, 24 and 48
Secondary	The Changes From Baseline in Fasting LDL to Weeks 24 and 48	Fasting LDL cholesterol changes from baseline to weeks 24 and 48 ( [week 24-baseline] and [week 48 - baseline], respectively).	Weeks 0, 24 and 48
Secondary	The Changes From Baseline in Urinary Phosphate Excretion to Weeks 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%	Weeks 0, 24 and 48
Secondary	The Changes From Baseline in CD4 to Weeks 4, 12, 24 and 48	Total CD4 count changes from baseline to weeks 4, 12, 24 and 48 [week 4/12/24/48 - baseline].	Weeks 0, 4, 12, 24 and 48
Secondary	The Changes From Baseline in iPTH to Weeks 24 and 48	iPTH (Parathyroid Hormone, intact) changes from baseline to weeks 24 and 48 ( [week 24-baseline] and [week 48 - baseline], respectively).	Weeks 0, 24 and 48