- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01966822
Multicentre Study To Assess Changes In Bone Mineral Density Of The Switch From Protease Inhibitors To Dolutegravir In HIV-1-Infected Subjects With Low Bone Mineral Density
MULTICENTRE STUDY TO ASSESS CHANGES IN BONE MINERAL DENSITY OF THE SWITCH FROM PROTEASE INHIBITORS TO DOLUTEGRAVIR IN HIV-1-INFECTED SUBJECTS WITH LOW BONE MINERAL DENSITY
Protease inhibitors (PI) have been associated with an acceleration of bone mineral density loss in HIV-infected individuals because of an enhanced osteoclast activity, although some controversial data have been also published. A first study suggest an increase of bone mineral density after switching from PI to raltegravir, the first generation integrase inhibitor, but there are no more data about this subject.
Based on data that PI decrease bone mineral density by accelerating osteoclast cells and that the discontinuation of this drugs could improve bone mineralization, we propose a randomized prospective multicenter study to assess the impact of switching from PI to dolutegravir on bone mineral density in patients with low bone mineral density receiving a PI-containing regimen. At the same time, the study will help to assess the antiviral efficacy and safety of a PI-sparing regimen including dolutegravir as a simplification strategy in virologically suppressed patients.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The second generation integrase inhibitor dolutegravir has demonstrated good virological and immunological outcomes in antiretroviral-naive subjects, compared with efavirenz, (SPRING 1 study). As well, it is active against HIV strains resistant to first-generation inhibitors raltegravir and elvitegravir in heavily treatment-experienced patients (VIKING study).
Additionally, it was safe and well tolerated after two years of use. It is administered once daily with no need for boosting, no food requirements and has a long half-life. The easy posology and its pharmacokinetics, together with the antiviral potency, make this drug a good alternative as a simplification approach. However, no clinical data are available supporting the switch of protease inhibitors or no nucleoside reverse transcriptase inhibitors to dolutegravir in virologically suppressed HIV-treated subjects.
Protease inhibitors (PI) have been associated with an acceleration of bone mineral density loss in HIV-infected individuals because of an enhanced osteoclast activity, although some controversial data have been also published. A first study suggest an increase of bone mineral density after switching from PI to raltegravir, the first generation integrase inhibitor, but there are no more data about this subject.
Based on data that PI decrease bone mineral density by accelerating osteoclast cells and that the discontinuation of this drugs could improve bone mineralization, we propose a randomized prospective multicenter study to assess the impact of switching from PI to dolutegravir on bone mineral density in patients with low bone mineral density receiving a PI-containing regimen. At the same time, the study will help to assess the antiviral efficacy and safety of a PI-sparing regimen including dolutegravir as a simplification strategy in virologically suppressed patients.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
-
Barcelona, Spain, 08025
- Hospital de la Santa Creu i Sant Pau
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Madrid, Spain, 28040
- Hospital Clinico San Carlos
-
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Barcelona
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Badalona, Barcelona, Spain, 08916
- GermansTrias i Pujol Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- HIV-infected patients over 18 years.
- In current antiretroviral therapy with abacavir and lamivudine (Kivexa) plus ritonavir-boosted PI, at least 6 months.
- Viral suppression (HIV RNA <50 copies / ml) for at least 12 months.
- T-score ≤ -1 evaluated by DEXA (done in the last 6 months).
- Signed informed consent.
- In potential childbearing women, commitment to use barrier contraceptive method throughout the study.
Exclusion Criteria:
- Suspected or documented resistance to integrase inhibitors or reverse transcriptase inhibitors, nucleoside analogues.
- Osteoporosis / osteopenia secondary (testosterone deficiency, thyroid disease ...), except vitamin D deficiency
- Treatment with bisphosphonates in the last 6 months.
- Have used integrase inhibitors
- Pregnant or breastfeeding.
- Patients with alanine aminotransferase (ALT)> 5 times the upper limit of normal (ULN) or ALT ≥ 3 times ULN and bilirubin ≥ 1.5 times ULN (direct bilirubin> 35%)
- Patients with severe hepatic dysfunction (Class B or C) according to the Child-Pugh classification
- Patients infected with hepatitis B virus (HBV) who can not use entecavir or telbivudine.
- Patients infected with hepatitis C virus (HCV) in which is expected to begin treatment during the study.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Dolutegravir 50mg
Dolutegravir 50mg every 24 hours + Kivexa (ABC+3TC)
|
Dolutegravir, 50mg every 24 hours
|
Active Comparator: Protease Inhibitor/ritonavir
Protease Inhibitor/ritonavir + Kivexa (ABC+3TC)
|
Protease Inhibitor/ritonavir
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Compare changes in Bone Mineral Density (BMO) measured by Dual-energy X-ray absorptiometry
Time Frame: From Baseline to week 48
|
From Baseline to week 48
|
Compare changes in femur T-score measured by DEXA
Time Frame: From Baseline to week 48
|
From Baseline to week 48
|
Compare changes in lumbar spine (L1-L4) T-score measured by DEXA
Time Frame: From Baseline to week 48
|
From Baseline to week 48
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
HIV-1 viral load
Time Frame: Baseline
|
Baseline
|
HIV-1 viral load
Time Frame: week 4
|
week 4
|
HIV-1 viral load
Time Frame: week 12
|
week 12
|
HIV-1 viral load
Time Frame: week 24
|
week 24
|
HIV-1 viral load
Time Frame: week 48
|
week 48
|
CD4+/CD8+ T lymphocytes count.
Time Frame: Baseline
|
Baseline
|
CD4+/CD8+ T lymphocytes count.
Time Frame: week 4
|
week 4
|
CD4+/CD8+ T lymphocytes count.
Time Frame: week 12
|
week 12
|
CD4+/CD8+ T lymphocytes count.
Time Frame: week 24
|
week 24
|
CD4+/CD8+ T lymphocytes count.
Time Frame: week 48
|
week 48
|
Genotypic test if virological failure occurs.
Time Frame: From baseline to week 48
|
From baseline to week 48
|
Compare changes in total cholesterol
Time Frame: at week 48 relative to baseline values
|
at week 48 relative to baseline values
|
Compare changes in HDL cholesterol
Time Frame: at week 48 relative to baseline values
|
at week 48 relative to baseline values
|
Compare changes in LDL cholesterol
Time Frame: at week 48 relative to baseline values
|
at week 48 relative to baseline values
|
Compare changes in triglyceride levels.
Time Frame: at week 48 relative to baseline values
|
at week 48 relative to baseline values
|
Compare changes in filtrate glomerular rate by MDRD equation
Time Frame: at week 48 relative to baseline values
|
at week 48 relative to baseline values
|
Compare changes in creatinine
Time Frame: at week 48 relative to baseline values
|
at week 48 relative to baseline values
|
Compare changes in albumine/creatinine ratio
Time Frame: at week 48 relative to baseline values
|
at week 48 relative to baseline values
|
Compare changes in proteinuria/creatinine ratio
Time Frame: at week 48 relative to baseline values
|
at week 48 relative to baseline values
|
Adverse events related to antiretroviral treatment (Toxicity).
Time Frame: From Baseline to week 48
|
From Baseline to week 48
|
Patient withdrawal
Time Frame: From Baseline to week 48
|
From Baseline to week 48
|
Compare changes in osteocalcin
Time Frame: at week 48 relative to baseline values
|
at week 48 relative to baseline values
|
Compare changes in alkaline phosphatase
Time Frame: at week 48 relative to baseline values
|
at week 48 relative to baseline values
|
Compare changes in telopeptide
Time Frame: at week 48 relative to baseline values
|
at week 48 relative to baseline values
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Metabolic Diseases
- Musculoskeletal Diseases
- Bone Diseases
- Bone Diseases, Metabolic
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Anti-HIV Agents
- Anti-Retroviral Agents
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 Enzyme Inhibitors
- HIV Integrase Inhibitors
- Integrase Inhibitors
- Viral Protease Inhibitors
- Ritonavir
- Protease Inhibitors
- Dolutegravir
- HIV Protease Inhibitors
Other Study ID Numbers
- OSTEODOLU
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