Renal, Endocrine, and Bone Changes in Response to FTC/TDF in Uninfected Young Men Who Have Sex With Men (YMSM).

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT01769469
First received: January 14, 2013
Last updated: May 8, 2014
Last verified: May 2014
  Purpose

This is a prospective observational cohort sub-study of subjects enrolled in ATN 110 or ATN 113, which is a prospective interventional trial.


Condition Intervention
HIV Infection
Drug: FTC/TDF (Truvada®)

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Renal, Endocrine, and Bone Changes in Response to Treatment With Coformulated Emtricitabine-Tenofovir for Pre-Exposure HIV Prophylaxis (PrEP) in HIV Uninfected Young Men Who Have Sex With Men. Sub-Study of Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) 110 and/or ATN 113

Resource links provided by NLM:


Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Primary Outcome Measures:
  • Magnitude of change in parathyroid hormone (PTH) from baseline to week 48 [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]
    The magnitude of change in PTH will be measured between Baseline and Week 48. The magnitude of change is the fold change compared to the baseline value. (If multiplied by 100 would be the percent change from baseline.)


Secondary Outcome Measures:
  • Change in renal-endocrine-bone biochemistry and pathophysiology [ Time Frame: Baseline, Weeks 4, 8, 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
    Change from baseline to week 48 in fibroblast growth factor 23 (FGF23), 1,25 dihydroxy vitamin D (1,25-OHD), tubular reabsorption of phosphate (TRP), and glomerular filtration rate (GFR); magnitude of fold change from baseline to weeks 4, 8, 12, 24, 36, and 48; most extreme fold change from baseline to weeks 4, 8, 12, 24, 36, and 48.

  • Time to most extreme fold change in PTH, FGF23, 1,25-OHD, TRP and serum creatinine (SCr) [ Time Frame: Baseline, Weeks 4, 8, 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
    Time to most extreme fold change in PTH, FGF23, 1,25-OHD, TRP, and SCr.

  • Change in renal-endocrine-bone biochemistry and pathophysiology (PTH, FGF23, 1,25-OHD, and TRP) [ Time Frame: Baseline, Weeks 4, 8, 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
    Time to most extreme fold change; slope between baseline and the most extreme fold change for PTH, FGF23, 1,25-OHD, and TRP.

  • Change in renal-endocrine-bone biochemistry and pathophysiology (PTH, FGF23, 1,25-OHD, and TRP) [ Time Frame: Baseline, Weeks 4, 8, 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
    Change from baseline, magnitude of most extreme fold change, and time to most extreme fold change from baseline in PTH, FGF23, 1,25-OHD, and TRP by race and baseline vitamin D status (25-OHD serum concentration).

  • Change in urine and serum calcium and phosphate (SCa, urine calcium (UCa)/urine creatinine (UCr), serum phosphate (SPO4), TRP) [ Time Frame: Baseline, Weeks 4, 8, 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
    Change from baseline, magnitude of most extreme, and time to most extreme fold change from baseline in urine and serum calcium and phosphate (SCa, UCa/UCr, SPO4, TRP).

  • Change in UCa/ UCr, SPO4, TRP versus changes in PTH, FGF23, 1,25-OHD [ Time Frame: Baseline, Weeks 4, 8, 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
    The association between (1) the time to most extreme fold change and slope of the curve of baseline to most extreme fold change in urine and serum calcium and phosphate (SCa, UCa/UCr, SPO4, TRP) and (2) the time to most extreme fold change and slope of the curve of baseline to most extreme fold change in PTH, FGF23, 1,25-OHD.

  • Change in glomerular and renal tubular function, urine retinol binding protein (URBP)/UCr, urine beta-2 microglobulin (UB2MG), urine protein (UProt)/Ucr. [ Time Frame: Baseline, Weeks 4, 8, 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
    Change from baseline, magnitude of most extreme fold change, and time to most extreme fold change, and slope of the curve of baseline to most extreme fold change in glomerular function (change in SCr from baseline) and renal tubular function (urine glucose (UGluc), URBP/UCr, UB2MG, UProt/UCr).

  • Change of TRP and markers of renal tubular function and endocrine change [ Time Frame: Baseline, Weeks 4, 8, 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
    Association between (1) change from baseline, magnitude of most extreme fold change, time to most extreme fold change, and slope of the curve of baseline to most extreme fold change of TRP and (2) markers of renal tubular function (UGluc, URBP/UCr, UB2MG, UProt/UCr) and markers of endocrine change (PTH, FGF23).

  • Change in renal-endocrine-bone biochemistry and pathophysiology [Bone alkaline phosphatase (BAP), osteocalcin (OC), C-telopeptide (CTX)] [ Time Frame: Baseline, Weeks 4, 8, 12, 24, and 48 ] [ Designated as safety issue: No ]
    Change from baseline, magnitude of most extreme fold change, time to most extreme fold change from baseline, and slope of the curve of baseline to most extreme fold change in markers of bone turnover (BAP, OC, CTX); association of these changes with endocrine controllers of calcium-phosphate balance (PTH, FGF23, 1,25-OHD), UCa/UCr, and TRP.

  • Change in renal-endocrine-bone biochemistry and pathophysiology (25-OHD, 1,25-OHD) [ Time Frame: Baseline, Weeks 4, 8, 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
    Association between (1) baseline values, changes from baseline, magnitude of most extreme fold change, and time to most extreme fold change from baseline, and slope of the curve of baseline to most extreme fold change for PTH, FGF23, 1,25-OHD, BAP, OC, CTX, SCr, UCa/UCr ratio, and TRP and (2) 25-OHD and 1,25-OHD serum concentrations.

  • Change in bone mass density (BMD) and bone mineral content (BMC) [ Time Frame: Baseline, Weeks 4, 24, and 48 ] [ Designated as safety issue: No ]
    Association between (1) the baseline values, magnitude of most extreme fold change, and time to most extreme fold change from baseline of the markers of bone turnover (BAP, OC, CTX) and endocrine controllers of calcium-phosphate balance (PTH, FGF23, 1,25-OHD) to the baseline values and (2) the magnitude of change in BMD/BMC from baseline to weeks 24 and 48.

  • Changes in markers of renal, endocrine, bone metabolism, and medication adherence [plasma or dried blood spot (DBS) emtricitabine (FTC), plasma or DBS tenofovir (TFV), red blood cell (RBC) tenofovir diphosphate (TFV-DP)] [ Time Frame: Baseline, Weeks, 4, 8, 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
    Association between (1) changes in concentration of markers of renal, endocrine, and bone metabolism and (2) markers of medication adherence.

  • Area under the drug concentration by time curve (AUC) for plasma or DBS FTC, plasma or DBS TFV, RBC TFV-DP; change from baseline to weeks 24 and 48 in PTH, FGF23, 1,25-OHD, BAP, OC, CTX, SCr, TRP, UCa/UCr ratio, UB2MG, UGluc, URBP/UCr ratio and BMD/BMC. [ Time Frame: Baseline, Weeks 4, 8, 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
    Association of AUC (over study duration) between (1) serum FTC, serum TFV, and RBC TFV-DP and change from baseline to weeks 24 and 48 in PTH, FGF23, 1,25-OHD, BAP, OC, CTX, SCr, TRP, UCa/UCr ratio, UB2MG, UGluc, URBP/UCr ratio and BMD/BMC.

  • Changes in PTH, FGF23, 1,25-OHD, BAP, OC, CTX, SCr, TRP, UCa/UCr ratio, UB2MG, UGluc, URBP/UCr ratio and BMD/BMC. [ Time Frame: Weeks 48, 72, and 96 ] [ Designated as safety issue: No ]
    For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit).


Biospecimen Retention:   Samples Without DNA

Blood and urine samples to measure:

Calcium-Phosphate Balance: Parathyroid hormone (PTH), Serum Calcium (SCa), Urine Calcium (UCa), Urine Creatinine (UCr), Serum Creatinine (SCr), Serum phosphate (SPO4), urine phosphate (UPO4), serum Fibroblast Growth Factor 23 (FGF23), vit D metabolites 25-OHD, 1,25-OHD, albumin, and magnesium (Mg).

Bone Turnover: Bone alkaline phosphatase (BAP), Osteocalcin (OC) and C-telopeptide (CTX) Renal Glomerular Function: SCr to calculate glomerular filtration rate (GFR) Renal Tubular Function: Urine Glucose (UGluc), Urine Retinol Binding Protein (URBP, Urine Beta-2 Microglobulin (UB2MG), Urine Protein (UProt) Dried blood spots (DBS) for FTC and Tenofovir (TFV)concentrations; red blood cell (RBC) for TFV-diphosphate (DP); plasma for FTC, TFV; peripheral blood mononuclear cells (PBMC) for TFV-DP and FTC-triphosphate (TP) collected as part of ATN 110 and ATN 113 will be used in the ATN 117 analysis.


Estimated Enrollment: 100
Study Start Date: November 2012
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Subjects Enrolled in ATN 110 or ATN 113
A subset of 100 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study.
Drug: FTC/TDF (Truvada®)
There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.
Other Name: Truvada®

Detailed Description:

This is a prospective observational cohort sub-study of subjects enrolled in the ATN 110 or ATN 113 study. All subjects will be followed for at least 48 weeks. Subjects who meet specific bone or renal criteria at Week 48 of the ATN 110 or ATN 113 study will be followed for an additional 48 weeks in the Extension Phase of ATN 110 or ATN 113 and ATN 117. The maximum duration of participation will be 96 weeks.

There is no therapeutic intervention specific to this sub-study, and there are no extra study visits required for participation in this sub-study. Questionnaires will be administered and blood and urine samples for laboratory evaluation of potential emtricitabine (FTC)/tenofovir (TDF) (Truvada®) toxicities will be obtained for this sub-study at visits that are required by the ATN 110 or ATN 113 study. Measurement of bone mineral density (BMD) and bone mineral content (BMC) by dual-energy X-ray absorptiometry (DXA) scan are planned as a part of the ATN 110 and ATN 113 studies, and results will be utilized for the analysis in this study. This study does not require extra BMD or BMC measurements.

  Eligibility

Ages Eligible for Study:   15 Years to 22 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Individuals between the ages 15 years 0 days to 22 years 364 days, who are enrolled in ATN 110 or ATN 113, and agree to enter this sub-study at the same time they begin ATN 110 or ATN 113.

Criteria

Inclusion Criteria:

  • Has been enrolled in ATN 110 or ATN 113, and
  • Willing and able to provide written informed consent

Exclusion Criteria:

-Subjects exempted from undergoing DXA scans in ATN 110 or ATN 113 are not eligible to enroll in ATN 117.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01769469

Locations
United States, California
Children's Hopsital of Los Angeles
Los Angeles, California, United States, 90027
United States, Colorado
Children's Hospital of Denver
Aurora, Colorado, United States, 80045
United States, Florida
University of Miami
Miami, Florida, United States, 33101
University of South Florida
Tampa, Florida, United States, 33606
United States, Illinois
Stroger Hospital and the CORE Center
Chicago, Illinois, United States, 60612
United States, Louisiana
Tulane University
New Orleans, Louisiana, United States, 70112
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Fenway Institute
Boston, Massachusetts, United States, 02215
United States, Michigan
Wayne State University
Detroit, Michigan, United States, 48201
United States, Pennsylvania
Children's Hopsital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
St. Jude Childrens Research Hospital
Memphis, Tennessee, United States, 38105
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
Sponsors and Collaborators
Investigators
Study Chair: Peter Havens, MD MACC Fund Research Center
  More Information

Additional Information:
No publications provided

Responsible Party: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier: NCT01769469     History of Changes
Other Study ID Numbers: ATN 117 version 2.0
Study First Received: January 14, 2013
Last Updated: May 8, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):
Tenofovir
Emtricitabine
Truvada
Renal, endocrine, bone changes
HIV prevention
PrEP

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Tenofovir
Emtricitabine
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on July 24, 2014