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WithdrawnNCT03549689ReNewUpdated Mar 15, 2021

Effect of Reducing Nucleotide Exposure on Bone Health (ReNew)

A Phase 2 interventional study of Dolutegravir (DTG) 50MG/lamivudine (3TC) 300MG FIXED DOSE COMBINATION (FDC) and Current tenofovir alafenamide (TAF)-containing ART regimen in HIV/AIDS, HIV-1-infection and Osteopenia, sponsored by Philip Grant. Withdrawn at 10 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-03-15.

Sponsored by Philip Grant · Phase 2, Interventional, and Treatment

Why this study was withdrawn
Withdrawn by drug manufacturer
Phase
Phase 2
Study type
Interventional
Enrollment
0
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

This is an open-label, randomized pilot study to assess the effect on bone mineral density (BMD) of a switch from a tenofovir alafenamide-containing antiretroviral regimen to dolutegravir/lamivudine vs. a continuation of the tenofovir alafenamide-containing regimen.

02

Conditions studied

  • HIV/AIDS
  • HIV-1-infection
  • Osteopenia
03

In context

Bone Diseases, Metabolic

470 studies on the registry are indexed under Bone Diseases, Metabolic; 71 are open to participants now.

Browse Bone Diseases, Metabolic studies →

Lead sponsor

Philip Grant is the lead sponsor of 2 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. HIV-1 infection, as documented by a positive 4th generation assay or by any licensed ELISA test kit confirmed by Western blot at any time prior to study entry.
  2. Age ≥18 years
  3. HIV-1 RNA BLQ (e.g., \<20 copies/mL or other threshold based on the local viral load assay used) for at least 12 months prior to study entry excluding blips (i.e., a single measurement \<200 copies/mL preceded and followed by measurements BLQ)
  4. On a stable TAF-containing ART that also includes at least 2 other antiretrovirals, with no changes in the 12 months prior to entry (except for a switch to a co-formulated tablet from the component tablets or a switch from ritonavir to cobicistat)
  5. Lumbar spine, femoral neck or total hip BMD T-score ≤-1.0 from a DXA scan within the past 48 weeks
  6. If receiving testosterone or estrogen replacement therapy, on a stable dose for ≥3 months prior to enrollment without plan to change dose during the study period.

  7. Acceptable blood laboratory values at screening visit:

    • CD4+ T-cell count ≥200 cells/µL
    • Phosphate ≥2mg/dL
    • 25-hydroxyvitamin D level ≥10 ng/ml

    • Calculated creatinine clearance (CrCl) ≥50 mL/min as estimated by the Cockcroft-Gault equation*:

      • For men = CrCl (mL/min) = (140 - age in years) x (body weight in kg) ÷ (serum creatinine in mg/dL x 72)

    For women, multiply the above result by 0.85

  8. For women of reproductive potential, negative serum or urine pregnancy test prior to screening and a negative urine pregnancy test at the entry visit prior to randomization and agreeable to using a contraceptive of choice during the study period.

"Women of reproductive potential" are defined as women who have not been post-menopausal for at least 24 consecutive months (i.e., who have had menses within the preceding 24 months) and have not undergone surgical sterilization (i.e., hysterectomy, bilateral oophorectomy, or tubal ligation; participant report sufficient)

Exclusion criteria

Exclusion Criteria:

  1. Current systemic glucocorticoid use
  2. Lumbar spine, femoral neck or total hip BMD T-score \<-3.0
  3. Previous, current pharmacologic treatment, or plan for initiation of therapy for osteoporosis (i.e., bisphosphonates, teriparatide, denosumab, tamoxifen or raloxifene)
  4. Previous fragility fracture (i.e., any fall from a standing height or less that resulted in a fracture)
  5. History of genotypic resistance or phenotypic resistance to either DTG or 3TC. The interpretation of genotypic resistance is based on output from the Stanford HIV Resistance Database (available at https://hivdb.stanford.edu). Isolates with an interpretation of low-level resistance or higher are considered resistant.
  6. History of virologic failure (i.e., confirmed HIV-1 RNA level ≥200 copies/mL after over 6 months of therapy) while on an integrase inhibitor (i.e., raltegravir, elvitegravir, bictegravir, or dolutegravir) or on lamivudine/emtricitabine prior to study enrollment. Any antiretroviral history (even before routine virologic monitoring became standard of care) that would suggest the presence of the M184V mutation should be considered exclusionary
  7. ALT ≥5 X ULN, OR ALT ≥3xULN and bilirubin ≥1.5xULN (with >35% direct bilirubin)
  8. Severe hepatic impairment (Child Pugh Class C)
  9. Anticipated need for antiviral therapy for HCV
  10. Hepatitis B surface antigen positive or Hepatitis B DNA positive
  11. Weight >300 pounds, precluding safe DXA testing
  12. Breastfeeding, pregnancy, or plans to become pregnant during the study
  13. Known allergy/sensitivity to DTG or 3TC.
  14. Receipt or planned receipt of prohibited concomitant medications (See section 5.4)
  15. Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study procedures and treatment.
  16. Any serious medical or psychiatric illness that, in the opinion of the site investigator, precludes safe participation or adherence to study procedures.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
0 participants (actual)

Study arms

  • Experimental
    Switch

    Dolutegravir (DTG) 50MG/ lamivuidne (3TC) 300MG FIXED_DOSE COMBINATION (FDC) DAILY at randomization for 96 weeks

    Drug: Dolutegravir (DTG) 50MG/lamivudine (3TC) 300MG FIXED DOSE COMBINATION (FDC)

  • Active comparator
    Continuation

    Continue current tenofovir alafenamide (TAF)-containing ART regimen from weeks 0 to 96.

    Drug: Current tenofovir alafenamide (TAF)-containing ART regimen

Interventions

  • DrugDolutegravir (DTG) 50MG/lamivudine (3TC) 300MG FIXED DOSE COMBINATION (FDC)

    Participants randomized to the Switch Arm will take DTG 50mg/3TC 300mg FDC once daily with or without food at approximately the same time each day.

  • DrugCurrent tenofovir alafenamide (TAF)-containing ART regimen

    Continuation of current TAF-containing ART for 96 weeks.

06

What researchers measure

Primary outcomes

  1. Percent change in lumbar spine Bone Mineral Density (BMD) at 96 weeks

    Compare the percentage change from entry to 96 weeks in lumbar spine BMD in those randomized to DTG/3TC vs. those continuing a TAF-based regimen

    Time frame: Baseline and 96 weeks

Secondary outcomes

  1. Percentage change in lumbar spine BMD at 48 weeks

    Compare the percentage change from entry to 48 weeks in lumbar spine BMD in those randomized to DTG/3TC vs. those continuing a TAF-based regimen

    Time frame: Baseline and 48 weeks

  2. Percentage change in total hip BMD at 48 weeks

    Compare the percentage change from entry to 48 weeks in total hip BMD in those randomized to DTG/3TC vs. those continuing a TAF-based regimen

    Time frame: Baseline, 48 weeks

  3. Percentage change in total hip BMD at 96 weeks

    Compare the percentage change from entry to 96 weeks in total hip BMD in those randomized to DTG/3TC vs. those continuing a TAF-based regimen

    Time frame: Baseline, 96 weeks

  4. Change in CTX (a bone resorption marker)

    Compare the changes in CTX from entry to 12, 48, and 96 weeks

    Time frame: Baseline, 12 weeks, 48 weeks, and 96 weeks

  5. Change in P1NP (a bone deposition marker)

    Compare the changes in P1NP from entry to 12, 48, and 96 weeks

    Time frame: Baseline, 12 weeks, 48 weeks, and 96 weeks

  6. Change in urine β2-microglobulin (renal tubular marker)

    Compare the changes in urine β2-microglobulin from entry to 48 weeks and 96 weeks.

    Time frame: Baseline, 48 weeks, and 96 weeks

  7. Change in urine RBP (renal tubular marker)

    Compare the changes in RBP from entry to 48 weeks and 96 weeks.

    Time frame: Baseline, 48 weeks, and 96 weeks

  8. Change in urine protein

    Compare the changes in protein from entry to 48 weeks and 96 weeks.

    Time frame: Baseline, 48 weeks, and 96 weeks

  9. Change in urine albumin

    Compare the changes in urine albumin from entry to 48 weeks and 96 weeks.

    Time frame: Baseline, 48 weeks, and 96 weeks

  10. Change in fractional excretion in phosphate

    Compare the changes in fractional excretion of phosphate from entry to 48 weeks and 96 weeks.

    Time frame: Baseline, 48 weeks, and 96 weeks

  11. Percentage change in total lean mass

    Compare the percentage change from entry to 48 weeks and 96 weeks in total lean mass (as measured by whole body DXA)

    Time frame: Baseline, 48 weeks, and 96 weeks

  12. Percentage change in trunk fat

    Compare the percentage change from entry to 48 weeks and 96 weeks in trunk fat (as measured by whole body DXA)

    Time frame: Baseline, 48 weeks, and 96 weeks

  13. Percentage change in limb fat

    Compare the percentage change from entry to 48 weeks and 96 weeks in limb fat (as measured by DXA)

    Time frame: Baseline, 48 weeks, and 96 weeks

  14. Maintenance of HIV RNA level

    Compare the levels of HIV RNA \<50 copies/mL and below the limit of quantification (BLQ) at 48 weeks and 96 weeks using the FDA snapshot algorithm

    Time frame: 48 weeks and 96 weeks

  15. Grade 3 or 4 adverse events

    Compare rates of grade 3 or 4 adverse events experienced by participants through 96 weeks

    Time frame: 96 weeks

  16. Treatment discontinuation of study medication due to adverse effect

    Compare treatment discontinuation of study medication due to adverse effect experienced by participants through 96 weeks

    Time frame: 96 weeks

  17. Change in fasting lipids

    Compare changes in fasting lipids (total cholesterol, LDL, HDL, and triglycerides) at entry, 48 weeks, and 96 weeks

    Time frame: Entry, 48 weeks, and 96 weeks

07

Study locations

10 sites
  • University of Alabama Birmingham
    Birmingham, Alabama 35233, United States
  • Stanford University
    Palo Alto, California 94305, United States
  • University of Colorado
    Aurora, Colorado 80045, United States
  • Emory
    Atlanta, Georgia 75440, United States
  • Northwestern
    Chicago, Illinois 60611, United States
  • Johns Hopkins
    Baltimore, Maryland 21287, United States
  • Columbia
    New York, New York 10032, United States
  • Penn
    Philadelphia, Pennsylvania 19104, United States
  • Dallas VA Medical Center
    Dallas, Texas 75216, United States
  • UT Houston
    Houston, Texas 77030, United States
08

References and documents

Individual participant data

Plan to share: Undecided

No publications or documents are linked to this record.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 15, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT03549689
Lead sponsor
Philip Grant
Responsible party
Philip Grant (Assistant Professor, Stanford University) — Sponsor-investigator
First posted
Jun 8, 2018
Start date
Aug 1, 2019 (estimated)
Primary completion
Jul 1, 2021 (estimated)
Completion
Jul 1, 2021 (estimated)
Last update
Mar 15, 2021

Study contacts

Philip Grant, MD
principal investigator · Stanford University

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is withdrawn, as verified in Mar 2021. You cannot join it, but the record below documents what was studied.

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