Vitamin D Absorption in HIV Infected Young Adults Being Treated With Tenofovir Containing cART

NCT01751646 | Completed Results DMC

• 1 other identifier: ATN 109 Version 2.0
• Study Type: interventional
• Target: 214
• Locations: 2 countries
• Sites: 17

Brief Summary

This is a 48 week randomized double-blind, placebo-controlled prospective cohort study of adolescents and young adults with HIV infection in the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) who are currently being treated with cART that includes tenofovir disoproxil fumarate (TDF) as one component of the regimen that includes at least three Food and Drug Administration (FDA)-approved antiretroviral (ARV) drugs for at least 180 days.

Conditions

HIV Infection

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline to Week 48 in Dual Energy X-ray Absorptiometry (DXA)-Measured BMD at the Spine for the Randomized Study Groups

  Percent change from baseline to week (wk) 48 in DXA-measured BMD at the spine for the randomized study groups. Lumbar spine BMD (L1 - L4) (g/cm2) change from Baseline to wk 48 visit.

  Baseline and wk 48

Secondary Outcomes (71)

• Percent Change From Baseline to Week 24 of BMC of Whole Body for the Randomized Study Groups

  Baseline and week 24

• Percent Change From Baseline to Week 48 of BMC of Whole Body for the Randomized Study Groups

  Baseline and week 48

• Percent Change From Baseline to Week 24 of Lumbar Spine (L1-L4) BMD for the Randomized Study Groups

  Baseline and week 24

• Change From Baseline to Week 24 of Lumbar Spine (L1-L4) BMD Z-score for the Randomized Study Groups

  Baseline and week 24

• Change From Baseline to Week 48 of Lumbar Spine (L1-L4) BMD Z-score for the Randomized Study Groups

  Baseline and week 48

Study Arms (2)

Group A: Vitamin D3 50,000 IU

EXPERIMENTAL

Subjects randomized to Group A will receive Vitamin D3 50,000 IU orally every four weeks by directly observed therapy (DOT). In addition all subjects receive a multivitamin (MVI) that contains ingredients not to exceed 600 IU of vitamin D3 and 200 mg of Calcium (Ca). Subjects will self-administer one MVI tablet orally once daily.

Dietary Supplement: Vitamin D3 50,000 IU

Group B: Vitamin D3 placebo

PLACEBO COMPARATOR

Subjects randomized to Group B will receive Vitamin D3 placebo orally every four weeks by DOT. In addition all subjects receive a MVI that contains ingredients not to exceed 600 IU of vitamin D3 and 200 mg of Ca. Subjects will self-administer one MVI tablet orally once daily.

Dietary Supplement: Vitamin D3 placebo

Interventions

Vitamin D3 50,000 IU DIETARY_SUPPLEMENT

Group A: Vitamin D3 50,000 IU orally every four weeks by DOT

Also known as: Vitamin D3

Group A: Vitamin D3 50,000 IU

Vitamin D3 placebo DIETARY_SUPPLEMENT

Group B: Vitamin D3 placebo orally every four weeks by DOT

Also known as: Placebo

Group B: Vitamin D3 placebo

Eligibility Criteria

• Age: 16 Years - 24 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• To be considered eligible for enrollment, an individual must meet the criteria listed below at the time of randomization:
• NOTE: If the DXA scan is scheduled prior to randomization, all eligibility criteria must be met prior to performing the DXA scan.
• Age 16 years and 0 days to 24 years and 364 days;
• Behaviorally infected with HIV (e.g., sexual contact, injection drug use; not infected by perinatal transmission, blood transfusion, or at age younger than 9 years);
• HIV-1 infection as documented in subject's medical record by at least one of the following criteria:
• reactive HIV screening test result with an antibody based FDA-licensed assay followed by a positive supplemental assay (e.g., HIV-1 Western Blot, HIV-1 Indirect Immunofluorescence, Antibody Differentiation Assay (Multispot)); or
• positive HIV-1 DNA polymerase chain reaction (PCR) assay; or
• plasma HIV-1 quantitative RNA assay \>1,000 copies/mL; or
• positive plasma HIV-1 RNA qualitative assay
• Subjects must have at least one documented HIV viral load that is below 200 copies/mL collected following initiation of TDF containing cART and greater than 90 days prior to randomization; no HIV viral load above 200 copies/mL if measured within the 90 days prior to randomization; and an HIV viral load obtained at screening that is below 200 copies/mL.
• Currently being treated for at least 180 days by the time of randomization with a TDF containing cART with at least 2 other FDA approved ARVs (NOTE: This may include a TDF-containing fixed drug combination medication);
• Negative serum hepatitis B surface antigen (HBsAg) at screening or by history within 4 weeks prior to screening (see section 7.1.3);
• Willingness and ability to remain on the same cART regimen for the duration of study participation;
• Willingness and ability to participate in the study, follow all study procedures for the duration of study participation, and provide written informed consent or assent with parental permission, if applicable; and
• For females of child-bearing potential, agreement to use a minimum of one proven-effective method of birth control and willingness to postpone pregnancy for the duration of study participation (see section 5.3.2 for permitted hormonal contraceptives)

You may not qualify if:

• To be considered eligible for enrollment, an individual must not meet any of the criteria listed below at the time of randomization:
• NOTE: If the DXA scan is scheduled prior to randomization, all eligibility criteria must be met prior to performing the DXA scan.
• Prior hypersensitivity to vitamin D;
• History of sarcoidosis, arteriosclerosis, renal stones, glomerulonephritis, interstitial kidney disease, nephrotic syndrome, hypercalcemia, osteoporosis and/or other bone diseases, clinical diagnosis of hypoparathyroidism or hyperparathyroidism;
• Lactation or pregnancy currently or within the past 24 weeks;
• Chemotherapy or radiation therapy for malignancy within the past 12 months;
• Known presence of GI disease that, in the opinion of the clinician, would interfere with study agent administration or absorption (e.g. Crohn's, Colitis);
• For subjects ≥ 18 years, confirmed creatinine clearance \< 70 ml/min (estimated glomerular filtration rate (GFR) from SCr using Cockcroft and Gault (CG) equation) and for subjects \<18 years, confirmed creatinine clearance \< 70ml/min/1.73m2 (estimated GFR from SCr using Schwartz formula (see section 3.5). (Estimated GFR may be calculated using the formulae programmed on the ATN website);
• SCa \> Upper Limit Normal (ULN) for local laboratory values (see section 7.1.3);
• Active Grade 3 or higher clinical or laboratory toxicity except atazanavir (ATV) associated indirect hyperbilirubinemia (see section 9.5.2.2);
• Weight is \> 350 pounds (lbs) or 159 kilograms (kgs);
• Positive hepatitis C antibody by history or at screening (see section 7.1.3); and
• Use of any medications as specified in sections 5.3.1, 5.3.3 and 5.4.
• Females Only: Use of certain hormonal contraceptives as specified in the protocol.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• National Institute on Drug Abuse (NIDA): collaborator
• National Institute of Mental Health (NIMH): collaborator

Study Sites (17)

Children's Hopsital of Los Angeles

Los Angeles, California, 90027, United States

Location

University of Southern California - NICHD Westat Site

Los Angeles, California, 90033, United States

Location

Childrens National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Children's Diagnostic and Treatment Center - NICHD Westat Site

Fort Lauderdale, Florida, 33316, United States

Location

University of Miami School of Medicine

Miami, Florida, 33101, United States

Location

University of South Florida

Tampa, Florida, 33606, United States

Location

Stroger Hospital and the CORE Center

Chicago, Illinois, 60612, United States

Location

Tulane Medical Center

New Orleans, Louisiana, 70112, United States

Location

Johns Hopkins University - NICHD Westat Site

Baltimore, Maryland, 21287, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Fenway Institute

Boston, Massachusetts, 02215, United States

Location

Wayne State University

Detroit, Michigan, 48201, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

St. Jude Childrens Research Hospital

Memphis, Tennessee, 38105, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

San Juan City Hospital (Puerto Rico) - NICHD Westat Site

San Juan, 00936-5067, Puerto Rico

Location

Related Publications (2)

• Havens PL, Stephensen CB, Van Loan MD, Schuster GU, Woodhouse LR, Flynn PM, Gordon CM, Pan CG, Rutledge B, Harris DR, Price G, Baker A, Meyer WA 3rd, Wilson CM, Hazra R, Kapogiannis BG, Mulligan K; Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) 109 Study Team. Vitamin D3 Supplementation Increases Spine Bone Mineral Density in Adolescents and Young Adults With Human Immunodeficiency Virus Infection Being Treated With Tenofovir Disoproxil Fumarate: A Randomized, Placebo-Controlled Trial. Clin Infect Dis. 2018 Jan 6;66(2):220-228. doi: 10.1093/cid/cix753.

  PMID: 29020329 RESULT

• Havens PL, Long D, Schuster GU, Gordon CM, Price G, Wilson CM, Kapogiannis BG, Mulligan K, Stephensen CB; Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) 117 and 109 study teams. Tenofovir disoproxil fumarate appears to disrupt the relationship of vitamin D and parathyroid hormone. Antivir Ther. 2018;23(7):623-628. doi: 10.3851/IMP3269. Epub 2018 Sep 27.

  PMID: 30260797 DERIVED

Related Links

• ATN website

MeSH Terms

Conditions

HIV Infections

Interventions

Cholecalciferol

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Limitations and Caveats

The analysis by efavirenz use and ritonavir use after baseline do not adjust for treatment group (secondary outcome measures 68, 69, 71, and 72). Results post-baseline may differ based on treatment group.

Results Point of Contact

• Title: Dr. Bob Harris
• Organization: Westat

bobharris@westat.com

301-251-1500

Study Officials

• Peter Havens, MD

  MACC Fund Research Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2012
• First Posted: December 18, 2012
• Study Start: October 1, 2012
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: March 27, 2019
• Results First Posted: March 11, 2019

Record last verified: 2018-11

Locations

US (16); PR (1)