Bone and Body Comp: A Sub Study of the SECOND-LINE Study

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Kirby Institute
ClinicalTrials.gov Identifier:
NCT01513122
First received: January 16, 2012
Last updated: December 1, 2013
Last verified: December 2013
  Purpose

The use of anti HIV drugs (ART), and in particular a class of drugs known as nucleoside reverse transcriptase inhibitors (N(t)RTI), has been associated with changes in body fat and in particular loss of peripheral fat in the limbs. Low bone mineral density and osteoporosis are also common in HIV-infected patients. There appears to be some association between ART and bone loss, but this is poorly understood and requires further research. The SECOND-LINE study provides an opportunity to examine if a new anti-HIV drug (raltegravir) can result in greater increase in limb fat than a drug regimen containing N(t)RTI, which is currently standard of care. This study also provides an opportunity to examine if additional bone loss occurs with the second regimen of anti-HIV drugs and whether non-N(t)RTI regimens of ART used in second line therapy result in more or less bone loss than use of other classes of anti-HIV drugs such as protease inhibitors or N(t)RTI combinations.

It is hypothesized that subjects randomised into Raltegravir arm will demonstrate greater increases in limb fat and smaller reductions in bone density at the proximal femur over 48 weeks than those randomised into the control arm (LPV/r + 2-3N(t)RTIs).


Condition Intervention Phase
HIV
Drug: Lopinavir / ritonavir + 2-3N(t)RTI
Drug: Lopinavir /ritonavir + raltegravir
Phase 4

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

Resource links provided by NLM:


Further study details as provided by Kirby Institute:

Primary Outcome Measures:
  • Mean Bone Mineral Density Changes Over 48 Weeks as Measured by DXA Scan [ Time Frame: May 2013 ] [ Designated as safety issue: No ]
  • Mean Limbs Fat Changes Over 48 Weeks as Measured by DXA Scan [ Time Frame: May 2013 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Mean Total Body Fat Changes Over 48 Weeks as Measured by DXA Scan [ Time Frame: May 2013 ] [ Designated as safety issue: No ]
  • Mean Triglycerides Changes Over 48 Weeks as Measured by DXA Scan [ Time Frame: May 2013 ] [ Designated as safety issue: No ]
  • Mean Total Cholesterol Changes Over 48 Weeks as Measured by DXA Scan [ Time Frame: May 2013 ] [ Designated as safety issue: No ]
  • Mean Glucose Changes Over 48 Weeks as Measured by DXA Scan [ Time Frame: May 2013 ] [ Designated as safety issue: No ]

Enrollment: 211
Study Start Date: February 2010
Study Completion Date: August 2013
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm 1. Lopinavir / ritonavir + 2-3N(t)RTI Drug: Lopinavir / ritonavir + 2-3N(t)RTI
LPV/r 200mg/50mg 4 tabs once daily or 2 tabs twice daily + 2-3 N(t)RTI
Active Comparator: Arm 2. Lopinavir /ritonavir + raltegravir Drug: Lopinavir /ritonavir + raltegravir
LPV/r 200mg/50mg 4 tabs once daily or 2 tabs twice daily + raltegravir 400mg 1 tablet twice daily.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Second-Line main study identifier: NCT00931463

Inclusion Criteria:

  1. HIV-1 positive by licensed diagnostic test
  2. Aged 16 years or older (or minimum age as determined by local regulations or as legal requirements dictate)
  3. Have received first antiretroviral regimen consisting of an NNRTI plus 2N(t)RTIs for ≥ 24 weeks
  4. No change in antiretroviral therapy within 12 weeks prior to screening
  5. Failed first-line NNRTI + 2N(t)RTI combination therapy according to virological criteria defined by two consecutive (≥7 days apart) HIV RNA results of > 500 copies/mL
  6. No prior or current exposure to HIV protease inhibitors and/or HIV integrase inhibitors
  7. Able to provide written informed consent

Exclusion Criteria:

  1. The following laboratory variables:

    • absolute neutrophil count (ANC) < 500 cells/µL
    • hemoglobin < 7.0 g/dL
    • platelet count < 50,000 cells/µL
    • ALT > 5 x ULN
  2. Pregnant or nursing mothers
  3. Participants with active viral hepatitis B infection defined by the presence in serum of hepatitis B surface antigen
  4. Use of immunomodulators within 30 days prior to screening
  5. Use of any prohibited medications (rifampicin, midazolam, triazolam, cisapride, pimozide, amiodarone, dihydroergotamine, ergotamine, ergonovine, methylergonovine, astemizole, terfenadine, vardenafil, and St. John's wort)
  6. Intercurrent illness requiring hospitalisation
  7. Active opportunistic disease not under adequate control in the opinion of the site Principal Investigator
  8. Participants with current alcohol or illicit substance abuse that in the opinion of the site Principal Investigator might adversely affect participation in the study
  9. Participants deemed by the site Principal Investigator unlikely to be able to remain in follow-up for the protocol-defined period
  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: NCT01513122

Locations
Argentina
CEADI
Buenos Aires, Argentina
India
YRGCare Medical Centre
Chennai, India, 600113
Malaysia
University of Malaya Medical Centre
Kuala Lumpur, Malaysia, 50603
South Africa
JOSHA Research
Bloemfontain, South Africa
Desmond Tutu HIV Foundation
Cape Town, South Africa, 7925
Chris Hani Baragwanath Hospital
Soweto, South Africa
Thailand
HIV-NAT Program on AIDS - Thai Red Cross
Bangkok, Thailand, 10330
Sponsors and Collaborators
Kirby Institute
Investigators
Principal Investigator: Paddy Mallon Mater Misericordiae University Hospital, Dublin
Principal Investigator: Waldo Belloso Hospital Italiano, Argentina
Principal Investigator: Samuel Ferret Hopital Saint-Louis, France
Principal Investigator: Praphan Phanuphak HIV-NAT Program on AIDS - Thai Red Cross, Bangkok
Principal Investigator: Jennifer Hoy The Alfred Hospital, Melbourne
  More Information

Publications:
Responsible Party: Kirby Institute
ClinicalTrials.gov Identifier: NCT01513122     History of Changes
Other Study ID Numbers: 2L body comp sub-study
Study First Received: January 16, 2012
Results First Received: December 1, 2013
Last Updated: December 1, 2013
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
South Africa: Medicines Control Council
India: Drugs Controller General of India

Additional relevant MeSH terms:
Lopinavir
Ritonavir
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protease Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014