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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04903847
Other study ID # H-20012194
Secondary ID
Status Recruiting
Phase Phase 4
First received
Last updated
Start date February 2, 2021
Est. completion date February 2, 2023

Study information

Verified date May 2021
Source Hvidovre University Hospital
Contact Karen BH Pedersen, MD
Phone +4521623027
Email karen.brorup.heje.pedersen@regionh.dk
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 126
Est. completion date February 2, 2023
Est. primary completion date February 2, 2023
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Dolutegravir/Lamivudine 50 MG-300 MG Oral Tablet [DOVATO]
Two-drug therapy
Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate 100 MG-300 MG-300 MG Oral Tablet [DELSTRIGO]
Three-drug therapy

Locations

Country Name City State
Denmark Department of Infectious Diseases, Aalborg University Hospital Aalborg
Denmark Department of Infectious Diseases, Aarhus University Hospital Aarhus
Denmark Department of Infectious Diseases, Rigshospitalet Copenhagen
Denmark Department of Infectious Diseases, Hvidovre University Hospital Hvidovre
Denmark Department of Infectious Diseases, Odense University Hospital Odense

Sponsors (1)

Lead Sponsor Collaborator
Thomas Benfield

Country where clinical trial is conducted

Denmark, 

References & Publications (14)

Bakal DR, Coelho LE, Luz PM, Clark JL, De Boni RB, Cardoso SW, Veloso VG, Lake JE, Grinsztejn B. Obesity following ART initiation is common and influenced by both traditional and HIV-/ART-specific risk factors. J Antimicrob Chemother. 2018 Aug 1;73(8):2177-2185. doi: 10.1093/jac/dky145. — View Citation

Belloso WH, Orellana LC, Grinsztejn B, Madero JS, La Rosa A, Veloso VG, Sanchez J, Ismerio Moreira R, Crabtree-Ramirez B, Garcia Messina O, Lasala MB, Peinado J, Losso MH. Analysis of serious non-AIDS events among HIV-infected adults at Latin American sites. HIV Med. 2010 Oct 1;11(9):554-64. doi: 10.1111/j.1468-1293.2010.00824.x. Epub 2010 Mar 21. — View Citation

Brown TT, Cole SR, Li X, Kingsley LA, Palella FJ, Riddler SA, Visscher BR, Margolick JB, Dobs AS. Antiretroviral therapy and the prevalence and incidence of diabetes mellitus in the multicenter AIDS cohort study. Arch Intern Med. 2005 May 23;165(10):1179-84. Erratum in: Arch Intern Med. 2005 Nov 28;165(21):2541. — View Citation

Burns JE, Stirrup OT, Dunn D, Runcie-Unger I, Milinkovic A, Candfield S, Lukha H, Severn A, Waters L, Edwards S, Gilson R, Pett SL. No overall change in the rate of weight gain after switching to an integrase-inhibitor in virologically suppressed adults with HIV. AIDS. 2020 Jan 1;34(1):109-114. doi: 10.1097/QAD.0000000000002379. — View Citation

Casado JL, Santiuste C, Vazquez M, Bañón S, Rosillo M, Gomez A, Perez-Elías MJ, Caballero C, Rey JM, Moreno S. Bone mineral density decline according to renal tubular dysfunction and phosphaturia in tenofovir-exposed HIV-infected patients. AIDS. 2016 Jun 1;30(9):1423-31. doi: 10.1097/QAD.0000000000001067. — View Citation

Gupta SK, Yeh E, Kitch DW, Brown TT, Venuto CS, Morse GD, Ha B, Melbourne K, McComsey GA. Bone mineral density reductions after tenofovir disoproxil fumarate initiation and changes in phosphaturia: a secondary analysis of ACTG A5224s. J Antimicrob Chemother. 2017 Jul 1;72(7):2042-2048. doi: 10.1093/jac/dkx076. — View Citation

Hill A, Waters L, Pozniak A. Are new antiretroviral treatments increasing the risks of clinical obesity? J Virus Erad. 2019 Jan 1;5(1):41-43. — View Citation

Jacobson DL, Spiegelman D, Knox TK, Wilson IB. Evolution and predictors of change in total bone mineral density over time in HIV-infected men and women in the nutrition for healthy living study. J Acquir Immune Defic Syndr. 2008 Nov 1;49(3):298-308. doi: 10.1097/QAI.0b013e3181893e8e. — View Citation

Koethe JR, Jenkins CA, Lau B, Shepherd BE, Justice AC, Tate JP, Buchacz K, Napravnik S, Mayor AM, Horberg MA, Blashill AJ, Willig A, Wester CW, Silverberg MJ, Gill J, Thorne JE, Klein M, Eron JJ, Kitahata MM, Sterling TR, Moore RD; North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). Rising Obesity Prevalence and Weight Gain Among Adults Starting Antiretroviral Therapy in the United States and Canada. AIDS Res Hum Retroviruses. 2016 Jan;32(1):50-8. doi: 10.1089/aid.2015.0147. Epub 2015 Sep 9. — View Citation

Nartey ET, Tetteh RA, Yankey BA, Mantel-Teeuwisse AK, Leufkens HGM, Dodoo ANO, Lartey M. Tenofovir-associated renal toxicity in a cohort of HIV infected patients in Ghana. BMC Res Notes. 2019 Jul 22;12(1):445. doi: 10.1186/s13104-019-4454-2. — View Citation

Nishijima T, Kawasaki Y, Tanaka N, Mizushima D, Aoki T, Watanabe K, Kinai E, Honda H, Yazaki H, Tanuma J, Tsukada K, Teruya K, Kikuchi Y, Gatanaga H, Oka S. Long-term exposure to tenofovir continuously decrease renal function in HIV-1-infected patients with low body weight: results from 10 years of follow-up. AIDS. 2014 Aug 24;28(13):1903-10. doi: 10.1097/QAD.0000000000000347. — View Citation

Sax PE, Erlandson KM, Lake JE, Mccomsey GA, Orkin C, Esser S, Brown TT, Rockstroh JK, Wei X, Carter CC, Zhong L, Brainard DM, Melbourne K, Das M, Stellbrink HJ, Post FA, Waters L, Koethe JR. Weight Gain Following Initiation of Antiretroviral Therapy: Risk Factors in Randomized Comparative Clinical Trials. Clin Infect Dis. 2020 Sep 12;71(6):1379-1389. doi: 10.1093/cid/ciz999. — View Citation

Smith CJ, Ryom L, Weber R, Morlat P, Pradier C, Reiss P, Kowalska JD, de Wit S, Law M, el Sadr W, Kirk O, Friis-Moller N, Monforte Ad, Phillips AN, Sabin CA, Lundgren JD; D:A:D Study Group. Trends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D): a multicohort collaboration. Lancet. 2014 Jul 19;384(9939):241-8. doi: 10.1016/S0140-6736(14)60604-8. — View Citation

Vizcarra P, Vivancos MJ, Pérez-Elías MJ, Moreno A, Casado JL. Weight gain in people living with HIV switched to dual therapy: changes in body fat mass. AIDS. 2020 Jan 1;34(1):155-157. doi: 10.1097/QAD.0000000000002421. — View Citation

* Note: There are 14 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary Body weight Primary outcome is a change in body weight of more than 2 kg from 48 Weeks
Secondary Virological control Plasma HIV-RNA <50 copies/ml 48 weeks
Secondary Self-rated health Changes in 12-item Short Form Health Survey (SF-12). Scores from 0 (worse) to 100 (best). 48 weeks
Secondary Insulin resistance Impaired insulin resistance and/or ß-cell function determined by changes in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) 48 weeks
Secondary Diabetic profile Changes in HbA1c 48 weeks
Secondary Cholesterol profile Changes in cholesterol total, HDL, LDL, VLDL 48 weeks
Secondary Fat distribution Changes in Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) determined by thoracic and upper abdominal CT-scan. 48 weeks
Secondary Hepatic elasticity Changes in hepativ elasticity determined by liver elastography (Fibro-scan) 48 weeks
Secondary Hepatic fat infiltration Changes in hepatic fat infiltration determined by liver elastography (Fibro-scan) and upper abdominal CT-scan 48 weeks
Secondary Body composition/perfiferal and central fat distribution Changes in body fat distribtuion determined bu Dual Energy X-ray Absorbtiometry (DEXA) 48 weeks
Secondary Estimated Glomerular Filtration Rate (eGFR) (creatinine) Changes in eGFR estimated by plasma creatinine 48 weeks
Secondary eGFR (cystatin) Changes in estimated by plasma cystatin 48 weeks
Secondary Urea Changes in plasma urea 48 weeks
Secondary Urine RBP/creatinine ratio Changes in Urine RBP/creatinine ratio determined by spot urine Retinol Binding Protein (RBP) and creatinine analysis 48 weeks
Secondary Urine Beta-2-Microglobulin(B2M)/creatinine ratio Changes in B2M/creatinine ratio determined by spot urine B2M and creatinine 48 weeks
Secondary Urine albumin/creatinine ratio Changes in Urine albumin/creatinine ratio determined by spot urine albumine and creatinine analysis 48 weeks
Secondary Urine protein/creatinine ratio Changes in urine protein/creatinine ratio determined by spot urine protein and creatinine analysis 48 weeks
Secondary Urine phosphate Changes in spot urine phosphate 48 weeks
Secondary Bone mass density (BMD) Changes in BMD assessed by DEXA 48 weeks
Secondary Bone-specific alkaline phosphate Changes in plasma Bone-specific alkaline phosphate 48 weeks
Secondary Procollagen type 1 N-pro-peptide Changes in procollagen type 1 N-pro-peptide 48 weeks
Secondary Type 1 collagen cross-linked C-telopeptide Changes in plasma Type 1 collagen cross-linked C-telopeptide 48 weeks
Secondary Osteocalcin Changes in plasma osteocalcin 48 weeks
Secondary Fasting ionized calcium Changes in plasma fasting ionized calcium 48 weeks
Secondary 25(OH)vitamin D vitamin D 25(OH)vitamin D Changes in plasma 25(OH)vitamin D 48 weeks
Secondary Parathyroid hormone (PTH) vitamin D 25(OH)vitamin D Changes in plasma parathyroid hormone (PTH) 48 weeks
Secondary Inflammation High-sensitive C-reactive protein 48 weeks
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