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Switching From Efavirenz to Atazanavir/ Ritonavir in HIV-infected Subjects With Good Virologic Suppression

This study has been terminated.
(Closed due to low enrollment)
Sponsor:
Collaborators:
National Institute of Allergy and Infectious Diseases (NIAID)
Case Western Reserve University
Bristol-Myers Squibb
Information provided by (Responsible Party):
Marisa Tungsiripat, The Cleveland Clinic
ClinicalTrials.gov Identifier:
NCT01194856
First received: September 2, 2010
Last updated: February 28, 2012
Last verified: February 2012
History of Changes
  Purpose

The purposes of this study are to evaluate if switching an antiretroviral medication from efavirenz (EFV) to atazanavir/ ritonavir (ARV/r) will, in a 96-week period, change:

  1. the amount of fat in HIV patients with lipoatrophy,
  2. metabolic lab values such as your lipid (fat) profile, glucose (blood sugar), and insulin (a hormone that regulates glucose) in HIV patients with lipoatrophy.

Condition Intervention Phase
HIV Infection
Mitochondrial Dysfunction
 Drug: Atazanavir/ritonavir
Drug: Efavirenz
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Study to Evaluate the Effect of Switching From Efavirenz to Atazanavir/ Ritonavir on Lipoatrophy and Mitochondrial Dysfunction in HIV-infected Subjects With Good Virologic Suppression

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by The Cleveland Clinic:

Primary Outcome Measures:
  • Change in DEXA-measured limb fat between the EFV and ATV/r arms [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    To examine the effect of switching from EFV- to ATV/r on limb fat in HIV-1 infected patients with established lipoatrophy, the primary objective of this trial will be to compare changes over 48 weeks in DEXA-measured limb fat between the EFV arm and ATV/r.


Secondary Outcome Measures:
  • Compare changes for DEXA-measured limb fat between EFV and ATV/r arms [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
    To examine the effect of switching from EFV- to ATV/r on limb fat in HIV-1 infected patients with established lipoatrophy, a secondary objective of this trial will be to compare changes over 96 weeks in DEXA-measured limb fat between the EFV arm and ARV/r.

  • Compare changes in CD4, HIV-1 RNA levels and adverse events in two arms [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]
    To examine the effect of switching from EFV to ATV/r on safety in HIV-1 infected patients, a secondary objective of this trial will be to compare changes over 96 weeks in CD4 cell count, HIV-1 RNA levels, and adverse events between the EFV arm and the ATV/r arm

  • Compare changes in fat mtDNA, mtRNA and fat apoptosis between the two arms [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
    To examine the effect of switching from EFV to ATV/r on fat mtDNA, mtRNA, and fat apoptosis in HIV-1 infected patients, a secondary objective of this trial will be to compare changes over 96 weeks in fat mtDNA, mt RNA levels and fat apoptosis between the EFV arm and ARV/r arm.

  • Comparing fasting lipid levels between the two arms [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
    To examine the effect of switching from EFV to ATV/r on lipids in HIV-1 infected patients, a secondary objective of this trial will be to compare changes over 96 weeks in fasting lipid levels between the EFV arm and ATV/r arm.

  • Comparing glucose metabolism (fasting insulin, QUIKI and HOMA-IR) between the two arms [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
    To examine the effect of switching from EFV to ATV/r on glucose metabolism in HIV-1 infected patients, a secondary objective of this trial will be to compare changes over 96 weeks in fasting insulin, QUIKI and HOMA-IR between the EFV arm and the ATV/r arm

  • Compare changes in levels of hs-CRP between the two arms [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
    To examine the effect of switching from EFV to ATV/r on highly sensitive C-reactive protein (hs-CRP) in HIV-1 infected patients, a secondary objective of this trial will be to compare changes over 96 weeks in hs (highly sensitive) - CRP levels between the EFV arm and the ATV/r arm.

  • Correlate the changes in DEXA-measured fat limb with fat mtDNA, mtRNA and fat apoptosis [ Time Frame: 96 weels ] [ Designated as safety issue: No ]
    A secondary objective of this trial will be to correlate the changes in DEXA-measured limb fat with those of fat mtDNA, mtRNA levels and fat apoptosis


Enrollment: 1
Study Start Date: October 2010
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Efavirenz 600 mg
Serving as the Control Arm - patients will maintain EFV-containing antiretroviral regimen
 Drug: Efavirenz
Maintain dosage - 600 mg orally QHS for 96 weeks
Other Name: Sustiva®: 50 mg, 200 mg
Experimental: Arm B - Atazanavir/Ritonavir
Atazanavir 300 mg orally with Ritonavir 100 mg orally once daily for 96 wks
 Drug: Atazanavir/ritonavir
300 mg orally once daily with Ritonavir 100mg orally once daily for 96 weeks
Other Names:
  • Reyataz®: 100 mg, 150 mg, 200 mg, 300 mg
  • Norvir®: 100 mg

Detailed Description:

Our study will evaluate the effects on peripheral fat of switching from EFV to ATV/r over 96 weeks in HIV+ patients with clinical lipoatrophy. From a virologic standpoint, EFV and ATV/r are medications which are recommended equally as preferred components of antiretroviral regimens in the December 2009 version of the Guidelines for the Use of Antiretroviral Agents in HIV-1 Infected Adults and Adolescents.[20] The study subjects should be receiving a stable EFV-containing antiretroviral (ART) regimen for at least 48 weeks prior to study entry. Blood will be saved for further investigations if needed. Safety parameters will be regularly assessed throughout the study. In addition, a subcutaneous fat biopsy will be obtained to measure fat mtDNA, mtRNA, and fat apoptosis. These measurements would provide significant insight into the clinical changes which have been recently described.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. HIV infection
  2. Age > or = 18 years old.
  3. Signed informed consent.
  4. Clinical lipoatrophy of at least moderate severity and in at least two different areas of the following: face, arms, legs, or buttocks (as self reported by the patient and confirmed by the physician).
  5. Women of childbearing potential must be using an adequate method of contraception to avoid pregnancy throughout the study in such a manner that the risk of pregnancy is minimized.

  6. All subjects must not participate in a conception process (e.g. active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization), and if participating in sexual activity that could lead to pregnancy, the female subject/ male partner must use condoms (male or female) in addition to one of the following forms of contraception while on study: either a spermicidal agent, diaphragm, cervical cap, IUD, or hormonal-based contraception.

    Prior to study enrollment, women of childbearing potential (WOCBP) must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. In addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of birth control.

  7. Receiving EFV-containing antiretroviral regimen for at least the last 48 weeks prior to study entry. Backbone NRTI regimens can include tenofovir, abacavir, emtricitabine, and/ or lamivudine. Backbone NRTI regimens cannot include zidovudine, stavudine, or didanosine. Breaks in therapy for a maximum of 5 consecutive days will be allowed during these 48 weeks, including the period immediately preceding study entry.
  8. Patient willing and able to stop aspirin/ NSAIDS for 7 days before study entry and the scheduled skin biopsy procedures.
  9. HIV-1 RNA < 400 copies/mL for at least 90 days prior to study entry.

  10. Laboratory values obtained within 60 days prior to study entry:

    1. Absolute neutrophil count (ANC) ≥ 500 / mm3
    2. Hemoglobin ≥ 9.0 g/dL
    3. Platelet count ≥ 75,000/ mm3
    4. Creatinine clearance > 50 mL / min
    5. PT/PTT < 1.2 ULN

Exclusion Criteria:

  1. Receipt of AZT, d4T, ddI, or ddC at study entry or within 24 weeks of entry
  2. Life expectancy < 12 months
  3. Women who are pregnant or breastfeeding
  4. WOCBP unwilling to use contraception WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period
  5. Women with a positive pregnancy test.
  6. Sexually active fertile men not using effective birth control if their partners are WOCBP.

  7. Other Exclusion Criteria

    1. Prisoners or subjects who are involuntarily incarcerated.
    2. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.
  8. Clinically important illness within 14 days prior to study entry
  9. Inability to communicate effectively with the study personnel.
  10. Bleeding diathesis
  11. Supplementation with recombinant growth hormone, growth hormone releasing factor, anabolic steroids, estrogen or testosterone, unless it is for replacement purposes.
  12. Have no plans to alter any vitamin supplementation that subjects are receiving at study entry. This includes all vitamin supplementation, coenzyme Q, N acetyl cysteine, L-acetyl carnitine, and uridine.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01194856

Locations
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
The Cleveland Clinic
National Institute of Allergy and Infectious Diseases (NIAID)
Case Western Reserve University
Bristol-Myers Squibb
Investigators
Principal Investigator: Marisa Tungsiripat, MD The Cleveland Clinic
  More Information

No publications provided

Responsible Party: Marisa Tungsiripat, Staff Physician, The Cleveland Clinic
ClinicalTrials.gov Identifier: NCT01194856     History of Changes
Other Study ID Numbers: 10-418, 5K23AI070078, BMS100MT
Study First Received: September 2, 2010
Last Updated: February 28, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by The Cleveland Clinic:
HIV
Lipoatrophy
mitochondrial dysfunction

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Ritonavir
Atazanavir
 Efavirenz
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on March 07, 2013