Trial record 11 of 34 for:    " September 30, 2013":" October 30, 2013"[FIRST-RECEIVED-DATE]AND HIV[CONDITION]

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Fundacio Lluita Contra la SIDA
Sponsor:
Information provided by (Responsible Party):
Fundacio Lluita Contra la SIDA
ClinicalTrials.gov Identifier:
NCT01966822
First received: October 7, 2013
Last updated: April 28, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
HIV-1 Infection
Drug: Dolutegravir, 50mg every 24 hours
Drug: Protease Inhibitor/ritonavir
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Fundacio Lluita Contra la SIDA:

Primary Outcome Measures:
  • Compare changes in Bone Mineral Density (BMO) measured by Dual-energy X-ray absorptiometry [ Time Frame: From Baseline to week 48 ] [ Designated as safety issue: Yes ]
  • Compare changes in femur T-score measured by DEXA [ Time Frame: From Baseline to week 48 ] [ Designated as safety issue: Yes ]
  • Compare changes in lumbar spine (L1-L4) T-score measured by DEXA [ Time Frame: From Baseline to week 48 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • HIV-1 viral load [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • HIV-1 viral load [ Time Frame: week 4 ] [ Designated as safety issue: No ]
  • HIV-1 viral load [ Time Frame: week 12 ] [ Designated as safety issue: No ]
  • HIV-1 viral load [ Time Frame: week 24 ] [ Designated as safety issue: No ]
  • HIV-1 viral load [ Time Frame: week 48 ] [ Designated as safety issue: No ]
  • CD4+/CD8+ T lymphocytes count. [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • CD4+/CD8+ T lymphocytes count. [ Time Frame: week 4 ] [ Designated as safety issue: No ]
  • CD4+/CD8+ T lymphocytes count. [ Time Frame: week 12 ] [ Designated as safety issue: No ]
  • CD4+/CD8+ T lymphocytes count. [ Time Frame: week 24 ] [ Designated as safety issue: No ]
  • CD4+/CD8+ T lymphocytes count. [ Time Frame: week 48 ] [ Designated as safety issue: No ]
  • Genotypic test if virological failure occurs. [ Time Frame: From baseline to week 48 ] [ Designated as safety issue: No ]
  • Compare changes in total cholesterol [ Time Frame: at week 48 relative to baseline values ] [ Designated as safety issue: Yes ]
  • Compare changes in HDL cholesterol [ Time Frame: at week 48 relative to baseline values ] [ Designated as safety issue: Yes ]
  • Compare changes in LDL cholesterol [ Time Frame: at week 48 relative to baseline values ] [ Designated as safety issue: Yes ]
  • Compare changes in triglyceride levels. [ Time Frame: at week 48 relative to baseline values ] [ Designated as safety issue: Yes ]
  • Compare changes in filtrate glomerular rate by MDRD equation [ Time Frame: at week 48 relative to baseline values ] [ Designated as safety issue: Yes ]
  • Compare changes in creatinine [ Time Frame: at week 48 relative to baseline values ] [ Designated as safety issue: Yes ]
  • Compare changes in albumine/creatinine ratio [ Time Frame: at week 48 relative to baseline values ] [ Designated as safety issue: Yes ]
  • Compare changes in proteinuria/creatinine ratio [ Time Frame: at week 48 relative to baseline values ] [ Designated as safety issue: Yes ]
  • Adverse events related to antiretroviral treatment (Toxicity). [ Time Frame: From Baseline to week 48 ] [ Designated as safety issue: Yes ]
  • Patient withdrawal [ Time Frame: From Baseline to week 48 ] [ Designated as safety issue: Yes ]
  • Compare changes in osteocalcin [ Time Frame: at week 48 relative to baseline values ] [ Designated as safety issue: Yes ]
  • Compare changes in alkaline phosphatase [ Time Frame: at week 48 relative to baseline values ] [ Designated as safety issue: Yes ]
  • Compare changes in telopeptide [ Time Frame: at week 48 relative to baseline values ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 80
Study Start Date: January 2014
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dolutegravir 50mg
Dolutegravir 50mg every 24 hours + Kivexa (ABC+3TC)
Drug: Dolutegravir, 50mg every 24 hours
Dolutegravir, 50mg every 24 hours
Active Comparator: Protease Inhibitor/ritonavir
Protease Inhibitor/ritonavir + Kivexa (ABC+3TC)
Drug: Protease Inhibitor/ritonavir
Protease Inhibitor/ritonavir

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. HIV-infected patients over 18 years.
  2. In current antiretroviral therapy with abacavir and lamivudine (Kivexa) plus ritonavir-boosted PI, at least 6 months.
  3. Viral suppression (HIV RNA <50 copies / ml) for at least 12 months.
  4. T-score ≤ -1 evaluated by DEXA (done in the last 6 months).
  5. Signed informed consent.
  6. In potential childbearing women, commitment to use barrier contraceptive method throughout the study.

Exclusion Criteria:

  1. Suspected or documented resistance to integrase inhibitors or reverse transcriptase inhibitors, nucleoside analogues.
  2. Osteoporosis / osteopenia secondary (testosterone deficiency, thyroid disease ...), except vitamin D deficiency
  3. Treatment with bisphosphonates in the last 6 months.
  4. Have used integrase inhibitors
  5. Pregnant or breastfeeding.
  6. 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%)
  7. Patients with severe hepatic dysfunction (Class B or C) according to the Child-Pugh classification
  8. Patients infected with hepatitis B virus (HBV) who can not use entecavir or telbivudine.
  9. Patients infected with hepatitis C virus (HCV) in which is expected to begin treatment during the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01966822

Locations
Spain
GermansTrias i Pujol Hospital Recruiting
Badalona, Barcelona, Spain, 08916
Contact: Negredo Eugenia, MD,PhD    93 465 78 97    enegredo@flsida.org   
Principal Investigator: Eugenia Negredo, MD,PhD         
Hospital de la Santa Creu i Sant Pau Recruiting
Barcelona, Spain, 08025
Contact: Pere Domingo, MD,PhD       PDomingo@santpau.cat   
Principal Investigator: Pere Domingo, MD,PhD         
Hospital Clínico San Carlos Recruiting
Madrid, Spain, 28040
Contact: Vicente Estrada, MD,PhD       vestradap@medynet.com   
Principal Investigator: Vicente Estrada, MD,PhD         
Sponsors and Collaborators
Fundacio Lluita Contra la SIDA
  More Information

No publications provided

Responsible Party: Fundacio Lluita Contra la SIDA
ClinicalTrials.gov Identifier: NCT01966822     History of Changes
Other Study ID Numbers: OSTEODOLU
Study First Received: October 7, 2013
Last Updated: April 28, 2014
Health Authority: Spain: Ministry of Health

Keywords provided by Fundacio Lluita Contra la SIDA:
Osteoporosis
Bone mineral density
Dual-energy X-ray absorptiometry
HIV infection
Dolutegravir
Integrase inhibitor

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Protease Inhibitors
Ritonavir
HIV Protease Inhibitors
Dolutegravir
Integrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
HIV Integrase Inhibitors

ClinicalTrials.gov processed this record on August 18, 2014