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: January 19, 2014
Last verified: January 2014

January 14, 2013
January 19, 2014
November 2012
November 2015   (final data collection date for primary outcome measure)
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.)
Same as current
Complete list of historical versions of study NCT01769469 on ClinicalTrials.gov Archive Site
  • 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).
  • 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 [serum emtricitabine (FTC), serum 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 serum FTC, serum 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, UB2MB, 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, UB2MB, UGluc, URBP/UCr ratio and BMD/BMC.
  • Changes in PTH, FGF23, 1,25-OHD, BAP, OC, CTX, SCr, TRP, UCa/UCr ratio, UB2MB, 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 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 study week 48 visit).
Not Provided
Not Provided
 
Renal, Endocrine, and Bone Changes in Response to FTC/TDF in Uninfected Young Men Who Have Sex With Men (YMSM).
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

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

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.

Observational
Observational Model: Cohort
Time Perspective: Prospective
Not Provided
Retention:   Samples Without DNA
Description:

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.

Non-Probability Sample

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.

HIV Infection
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®
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.
Intervention: Drug: FTC/TDF (Truvada®)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
100
November 2015
November 2015   (final data collection date for primary outcome measure)

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.

Male
15 Years to 22 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01769469
ATN 117 version 2.0
No
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Not Provided
Study Chair: Peter Havens, MD MACC Fund Research Center
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP