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

NCT ID: NCT01751646

Last Updated: 2019-03-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 214 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2016-06-30

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.

Detailed Description

This is a 48 week randomized double-blind, placebo-controlled prospective cohort study of adolescents and young adults with HIV infection in the ATN who are currently being treated with cART that includes TDF as one component of the regimen that includes at least three Food and Drug Administration (FDA)-approved ARVs for at least 180 days. Subjects must have at least one documented viral load that is below 200 copies/mL that is collected following initiation of TDF containing cART and greater than 90 days prior to randomization; no 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.

Treatment assignments will be balanced by subject sex at birth, age (<20 years vs. >=20 years), and race (African American vs. other). Enrolled subjects will be randomized to receive vitamin D3 50000 IU or matching placebo, given orally every four weeks by DOT. In addition to the randomized study agent, all subjects will receive a MVI to be taken orally once daily. This "standard" MVI will contain ingredients not to exceed 600 IU of vitamin D3 and 200 mg Ca.

Dual energy x-ray absorptiometry (DXA) measurement of bone mineral content (BMC)/bone mineral density (BMD) of whole body, spine, and hip, will be performed at baseline and study weeks 24 and 48. Blood and urine sampling to assess the Ca-phosphorous (PO4) axis, parathyroid hormone (PTH)-FGF23-vitamin D signaling, bone turnover, and renal glomerular and tubular function will occur at baseline and study weeks 12, 24, and 48. Blood samples to measure Gluc homeostasis will be drawn at baseline and week 48, and will be run by batch analysis.

Safety, measured by serum calcium (SCa) and serum creatinine (SCr), will be monitored by subject's record review at study sites since these labs will generally be measured as a part of routine clinical care. The Adolescent Medicine Trials Network for HIV/AIDS Interventions 109 (ATN 109) study will use the SCa and SCr values obtained within 10 weeks at the time of the visit beginning at the baseline visit. If these evaluations were not performed within the prior 10 weeks they will be drawn at the time of each visit. Viral load and cluster of differentiation 4 (CD4) cell count results will be recorded for this study, ATN 109, at screening, baseline and study weeks 12, 24, 48, and Post-Week 48 provided the evaluations were done within the protocol specified timeframe. If the evaluations were not performed within the protocol specified timeframes they will be drawn at the time of the visit.

Conditions

HIV Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: TRIPLE

Study Groups

Group A: Vitamin D3 50,000 IU

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.

Group Type: EXPERIMENTAL

Vitamin D3 50,000 IU

Intervention Type: DIETARY_SUPPLEMENT

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

Group B: Vitamin D3 placebo

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.

Group Type: PLACEBO_COMPARATOR

Vitamin D3 placebo

Intervention Type: DIETARY_SUPPLEMENT

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

Interventions

Vitamin D3 50,000 IU

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

Intervention Type: DIETARY_SUPPLEMENT

Vitamin D3 placebo

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

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

Vitamin D3; Placebo

Eligibility Criteria

Inclusion Criteria

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)

Exclusion Criteria

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.

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 24 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Peter Havens, MD

Role: STUDY_CHAIR

MACC Fund Research Center

Locations

Children's Hopsital of Los Angeles

Los Angeles, California, United States

University of Southern California - NICHD Westat Site

Los Angeles, California, United States

Childrens National Medical Center

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

Children's Diagnostic and Treatment Center - NICHD Westat Site

Fort Lauderdale, Florida, United States

University of Miami School of Medicine

Miami, Florida, United States

University of South Florida

Tampa, Florida, United States

Stroger Hospital and the CORE Center

Chicago, Illinois, United States

Tulane Medical Center

New Orleans, Louisiana, United States

Johns Hopkins University - NICHD Westat Site

Baltimore, Maryland, United States

Johns Hopkins University

Baltimore, Maryland, United States

Fenway Institute

Boston, Massachusetts, United States

Wayne State University

Detroit, Michigan, United States

Montefiore Medical Center

The Bronx, New York, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

St. Jude Childrens Research Hospital

Memphis, Tennessee, United States

Baylor College of Medicine

Houston, Texas, United States

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

San Juan, , Puerto Rico

Countries

United States; Puerto Rico

References

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.

Reference Type: RESULT

PMID: 29020329 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30260797 (View on PubMed)

Related Links

http://www.atnonline.org

ATN website

Other Identifiers

ATN 109 Version 2.0

Identifier Type: -

Identifier Source: org_study_id