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Changes in Weight, Body Composition and Metabolic Parameters After Discontinuing Dolutegravir or Tenofovir Disproxil (AVERTAS-2)

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ClinicalTrials.gov Identifier: NCT04903847
Recruitment Status : Recruiting
First Posted : May 27, 2021
Last Update Posted : May 27, 2021
Sponsor:
Information provided by (Responsible Party):
Thomas Benfield, Hvidovre University Hospital

Brief Summary:
Randomized controlled parallel open-label study in persons living with HIV. The aim is to study weight changes in patients switching from a dolutegravir and tenofovir disoproxil containing regimen to either a dolutegravir or tenofovir disoproxil free regimen.

Condition or disease Intervention/treatment Phase
Hiv HIV Infections HIV Lipodystrophy Osteoporosis Renal Insufficiency Weight Gain Obesity Drug: Dolutegravir/Lamivudine 50 MG-300 MG Oral Tablet [DOVATO] Drug: Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate 100 MG-300 MG-300 MG Oral Tablet [DELSTRIGO] Phase 4

Detailed Description:

Randomized controlled parallel open-label study in persons living with HIV and at least 6 month of treatment with dolutegravir/abacavir/lamivudine prior to inclusion.

Participants (n=126) are randomized to continue 3 drug-regimen dolutegravir/tenofovir disoproxil/lamivudine (control) or switch to two-drug regimen with dolutegravir/lamivudine (intervention 1) or to three-drug regimen with doravirine/tenofovir disoproxil/lamivudine. Follow-up is 48 weeks. Data is collected at baseline and week 48.

Primary outcome is changes in weight from baseline of more than 2 kg.

Secondary outcomes are virus persistent viral suppression, changes in body composition and metabolism, changes in bone metabolisme and renal function, changes in liver elasticity and fat infiltration.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 126 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized controlled open-label superiority trial
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Changes in Weight After Switch to Dolutegravir/Lamivudine or Doravirine/Tenofovir/Lamivudine Compared to Continued Treatment With Dolutegravir/Tenofovir/Lamivudine for Virologically Suppressed HIV Infection. AVERTAS-2
Actual Study Start Date : February 2, 2021
Estimated Primary Completion Date : February 2, 2023
Estimated Study Completion Date : February 2, 2023


Arm Intervention/treatment
No Intervention: Dolutegravir/tenofovir disproxil/lamivudine
Continue dolutegravir 50 mg, tenofovir disproxil 245 mg, ,and lamivudine 300 mg once daily for 48 weeks.
Experimental: dolutegravir/lamivudine
dolutegravir 50 mg/lamivudine 300 mg once daily for 48 weeks
Drug: Dolutegravir/Lamivudine 50 MG-300 MG Oral Tablet [DOVATO]
Two-drug therapy
Other Name: Dovato

Experimental: doravirine/tenofovir disproxil/lamivudine
100 mg doravirin, 245 mg tenofovirdisoproxil and 300 mg lamivudine once daily for 48 weeks.
Drug: Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate 100 MG-300 MG-300 MG Oral Tablet [DELSTRIGO]
Three-drug therapy
Other Name: Delstrigo




Primary Outcome Measures :
  1. Body weight [ Time Frame: 48 Weeks ]
    Primary outcome is a change in body weight of more than 2 kg from


Secondary Outcome Measures :
  1. Virological control [ Time Frame: 48 weeks ]
    Plasma HIV-RNA <50 copies/ml

  2. Self-rated health [ Time Frame: 48 weeks ]
    Changes in 12-item Short Form Health Survey (SF-12). Scores from 0 (worse) to 100 (best).

  3. Insulin resistance [ Time Frame: 48 weeks ]
    Impaired insulin resistance and/or β-cell function determined by changes in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)

  4. Diabetic profile [ Time Frame: 48 weeks ]
    Changes in HbA1c

  5. Cholesterol profile [ Time Frame: 48 weeks ]
    Changes in cholesterol total, HDL, LDL, VLDL

  6. Fat distribution [ Time Frame: 48 weeks ]
    Changes in Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) determined by thoracic and upper abdominal CT-scan.

  7. Hepatic elasticity [ Time Frame: 48 weeks ]
    Changes in hepativ elasticity determined by liver elastography (Fibro-scan)

  8. Hepatic fat infiltration [ Time Frame: 48 weeks ]
    Changes in hepatic fat infiltration determined by liver elastography (Fibro-scan) and upper abdominal CT-scan

  9. Body composition/perfiferal and central fat distribution [ Time Frame: 48 weeks ]
    Changes in body fat distribtuion determined bu Dual Energy X-ray Absorbtiometry (DEXA)

  10. Estimated Glomerular Filtration Rate (eGFR) (creatinine) [ Time Frame: 48 weeks ]
    Changes in eGFR estimated by plasma creatinine

  11. eGFR (cystatin) [ Time Frame: 48 weeks ]
    Changes in estimated by plasma cystatin

  12. Urea [ Time Frame: 48 weeks ]
    Changes in plasma urea

  13. Urine RBP/creatinine ratio [ Time Frame: 48 weeks ]
    Changes in Urine RBP/creatinine ratio determined by spot urine Retinol Binding Protein (RBP) and creatinine analysis

  14. Urine Beta-2-Microglobulin(B2M)/creatinine ratio [ Time Frame: 48 weeks ]
    Changes in B2M/creatinine ratio determined by spot urine B2M and creatinine

  15. Urine albumin/creatinine ratio [ Time Frame: 48 weeks ]
    Changes in Urine albumin/creatinine ratio determined by spot urine albumine and creatinine analysis

  16. Urine protein/creatinine ratio [ Time Frame: 48 weeks ]
    Changes in urine protein/creatinine ratio determined by spot urine protein and creatinine analysis

  17. Urine phosphate [ Time Frame: 48 weeks ]
    Changes in spot urine phosphate

  18. Bone mass density (BMD) [ Time Frame: 48 weeks ]
    Changes in BMD assessed by DEXA

  19. Bone-specific alkaline phosphate [ Time Frame: 48 weeks ]
    Changes in plasma Bone-specific alkaline phosphate

  20. Procollagen type 1 N-pro-peptide [ Time Frame: 48 weeks ]
    Changes in procollagen type 1 N-pro-peptide

  21. Type 1 collagen cross-linked C-telopeptide [ Time Frame: 48 weeks ]
    Changes in plasma Type 1 collagen cross-linked C-telopeptide

  22. Osteocalcin [ Time Frame: 48 weeks ]
    Changes in plasma osteocalcin

  23. Fasting ionized calcium [ Time Frame: 48 weeks ]
    Changes in plasma fasting ionized calcium

  24. 25(OH)vitamin D vitamin D 25(OH)vitamin D [ Time Frame: 48 weeks ]
    Changes in plasma 25(OH)vitamin D

  25. Parathyroid hormone (PTH) vitamin D 25(OH)vitamin D [ Time Frame: 48 weeks ]
    Changes in plasma parathyroid hormone (PTH)

  26. Inflammation [ Time Frame: 48 weeks ]
    High-sensitive C-reactive protein



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Individuals ≥ 18 years old with diagnosed HIV and at least 6 months of ongoing treatment with dolutegravir/ doravirin/lamivudine will be included. Patients must have a plasma viral load (HIV-RNA) < 50 copies/ml at inclusion. For women of childbearing potential: Negative pregnancy test and willingness to use contraceptive (consistent with local regulations) during study period

Exclusion Criteria:

  • Patients will be excluded in case of pre-existing viral resistance mutations to lamivudine, dolutegravir, tenofovir or doravirine the presence of hepatitis B antigen (HBsAg) or HBV DNA, cancer within past 5 years, pregnancy or breastfeeding. Any case of diabetes, cardiovascular disease or other chronic illness must be considered stable as assessed by the treating physician.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04903847


Contacts
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Contact: Karen BH Pedersen, MD +4521623027 karen.brorup.heje.pedersen@regionh.dk
Contact: Thomas Benfield, MD thomas.lars.benfield@regionh.dk

Locations
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Denmark
Department of Infectious Diseases, Aalborg University Hospital Not yet recruiting
Aalborg, Denmark, 9000
Contact: Henrik Nielsen, MD, DMSc         
Department of Infectious Diseases, Aarhus University Hospital Not yet recruiting
Aarhus, Denmark, 8200
Contact: Alex L Laursen, MD, PhD         
Department of Infectious Diseases, Rigshospitalet Not yet recruiting
Copenhagen, Denmark, 2100
Contact: Jan Gerstoft, MD, DMSc         
Department of Infectious Diseases, Hvidovre University Hospital Recruiting
Hvidovre, Denmark, 2650
Contact: Karen BH Pedersen, MD    +4521623027    karen.brorup.heje.pedersen@regionh.dk   
Department of Infectious Diseases, Odense University Hospital Not yet recruiting
Odense, Denmark, 5000
Contact: Isik S Johansen, MD, DMSc         
Sponsors and Collaborators
Thomas Benfield
Investigators
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Study Director: Thomas Benfield, MD Center of Research and Disruption of Infectious Diseases
Publications:

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Responsible Party: Thomas Benfield, MD, professor, dr.med., Hvidovre University Hospital
ClinicalTrials.gov Identifier: NCT04903847    
Other Study ID Numbers: H-20012194
First Posted: May 27, 2021    Key Record Dates
Last Update Posted: May 27, 2021
Last Verified: May 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Thomas Benfield, Hvidovre University Hospital:
HIV
antiretroviral therapy
antiretroviral therapy adverse events
weight gain
body composition
fat distribution
Additional relevant MeSH terms:
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Infections
HIV Infections
Acquired Immunodeficiency Syndrome
Osteoporosis
Renal Insufficiency
Lipodystrophy
Body Weight
Weight Gain
Blood-Borne Infections
Communicable Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Metabolic Diseases
Body Weight Changes
Kidney Diseases
Urologic Diseases
Skin Diseases, Metabolic
Skin Diseases
Lipid Metabolism Disorders
Tenofovir