HIV InfectionPhase 4NCT01194856
Switching From Efavirenz to Atazanavir/ Ritonavir in HIV-infected Subjects With Good Virologic Suppression
A Phase 4 study testing Atazanavir/ritonavir and Efavirenz in people with HIV Infection and Mitochondrial Dysfunction, run by The Cleveland Clinic at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- HIV Infection, Mitochondrial Dysfunction
- What is being tested?
- Atazanavir/ritonavir and Efavirenz
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2010to Dec 2011
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV infection
- Age > or = 18 years old.
- Signed informed consent.
- 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).
- 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.
- 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.
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- 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.
- 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.
- Patient willing and able to stop aspirin/ NSAIDS for 7 days before study entry and the scheduled skin biopsy procedures.
- HIV-1 RNA < 400 copies/mL for at least 90 days prior to study entry.
- Laboratory values obtained within 60 days prior to study entry:
- Absolute neutrophil count (ANC) ≥ 500 / mm3
- Hemoglobin ≥ 9.0 g/dL
- Platelet count ≥ 75,000/ mm3
- Creatinine clearance > 50 mL / min
- PT/PTT < 1.2 ULN
Who cannot join
- Receipt of AZT, d4T, ddI, or ddC at study entry or within 24 weeks of entry
- Life expectancy < 12 months
- Women who are pregnant or breastfeeding
- WOCBP unwilling to use contraception WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period
- Women with a positive pregnancy test.
- Sexually active fertile men not using effective birth control if their partners are WOCBP.
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- Other Exclusion Criteria
- Prisoners or subjects who are involuntarily incarcerated.
- Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.
- Clinically important illness within 14 days prior to study entry
- Inability to communicate effectively with the study personnel.
- Bleeding diathesis
- Supplementation with recombinant growth hormone, growth hormone releasing factor, anabolic steroids, estrogen or testosterone, unless it is for replacement purposes.
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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:
- the amount of fat in HIV patients with lipoatrophy,
- metabolic lab values such as your lipid (fat) profile, glucose (blood sugar), and insulin (a hormone that regulates glucose) in HIV patients with lipoatrophy.
Read the 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.
- Conditions
- HIV Infection, Mitochondrial Dysfunction
- Being tested
- Atazanavir/ritonavir, Efavirenz
- Keywords
- HIV, Lipoatrophy, mitochondrial dysfunction
- Medical subject headings
- HIV Infections, Mitochondrial Diseases, Lipodystrophy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Atazanavir/ritonavirDrug
Also called Reyataz®: 100 mg, 150 mg, 200 mg, 300 mg, Norvir®: 100 mg
300 mg orally once daily with Ritonavir 100mg orally once daily for 96 weeks
EfavirenzDrug
Also called Sustiva®: 50 mg, 200 mg
Maintain dosage - 600 mg orally QHS for 96 weeks
| Study group | Role | What they receive |
|---|---|---|
| Efavirenz 600 mg | Active comparator | Serving as the Control Arm - patients will maintain EFV-containing antiretroviral regimen Receives: Drug: Efavirenz |
| Arm B - Atazanavir/Ritonavir | Experimental | Atazanavir 300 mg orally with Ritonavir 100 mg orally once daily for 96 wks Receives: Drug: Atazanavir/ritonavir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in DEXA-measured Limb Fat Between the EFV and ATV/r Arms
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.
Measured: 48 weeks
Secondary outcomes (7)
Compare Changes for DEXA-measured Limb Fat Between EFV and ATV/r Arms
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.
Measured: 96 weeks
Compare Changes in CD4, HIV-1 RNA Levels and Adverse Events in Two Arms
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
Measured: 96 weeks
Compare Changes in Fat mtDNA, mtRNA and Fat Apoptosis Between the Two Arms
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.
Measured: 96 weeks
Comparing Fasting Lipid Levels Between the Two Arms
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.
Measured: 96 weeks
Comparing Glucose Metabolism (Fasting Insulin, QUIKI and HOMA-IR) Between the Two Arms
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
Measured: 96 weeks
Compare Changes in Levels of Hs-CRP Between the Two Arms
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.
Measured: 96 weeks
Correlate the Changes in DEXA-measured Fat Limb With Fat mtDNA, mtRNA and Fat Apoptosis
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
Measured: 96 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2010 (estimated)
- Study startOct 2010
- Primary completionDec 2011
- Study completionDec 2011
Why it stopped: Closed due to low enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HIV InfectionStudies of the same condition, open and under way.
- More trials run by The Cleveland ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Cleveland Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), Case Western Reserve University, Bristol-Myers Squibb
- Responsible party
- Principal investigator, Marisa Tungsiripat, The Cleveland Clinic
- Investigators
- Marisa Tungsiripat, MD, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01194856
- Sponsor's protocol ID
- 10-418
- Other IDs
- 5K23AI070078, BMS100MT
- Status last verified
- Aug 2017
- First submitted
- 2 Sep 2010
- Last updated
- 11 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01194856
- Acronym / sponsor ID
- 10-418
- Conditions
- HIV Infection, Mitochondrial Dysfunction
- Keywords
- HIV, Lipoatrophy, mitochondrial dysfunction
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Closed due to low enrollment
- Enrolment
- 1 participants (actual)
- Lead sponsor
- The Cleveland ClinicUniversity, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), Case Western Reserve University, Bristol-Myers Squibb
- Study start
- Oct 2010
- Primary completion
- Dec 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 3 Sep 2010 (estimated)
- Results
- Posted 11 Aug 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- the amount of fat in HIV patients with lipoatrophy,
- metabolic lab values such as your lipid (fat) profile, glucose (blood sugar), and insulin (a hormone that regulates glucose) in HIV patients with lipoatrophy.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Efavirenz 600 mg | Active comparator | Drug: EfavirenzServing as the Control Arm - patients will maintain EFV-containing antiretroviral regimen |
| Arm B - Atazanavir/Ritonavir | Experimental | Drug: Atazanavir/ritonavirAtazanavir 300 mg orally with Ritonavir 100 mg orally once daily for 96 wks |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- HIV infection
- Age > or = 18 years old.
- Signed informed consent.
- 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).
- 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.
Key exclusion criteria (14 listed)
- Receipt of AZT, d4T, ddI, or ddC at study entry or within 24 weeks of entry
- Life expectancy < 12 months
- Women who are pregnant or breastfeeding
- WOCBP unwilling to use contraception WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period
- Women with a positive pregnancy test.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Atazanavir/ritonavirAlso: Reyataz®: 100 mg, 150 mg, 200 mg, 300 mg, Norvir®: 100 mg300 mg orally once daily with Ritonavir 100mg orally once daily for 96 weeks | Drug | Arm B - Atazanavir/Ritonavir |
| EfavirenzAlso: Sustiva®: 50 mg, 200 mgMaintain dosage - 600 mg orally QHS for 96 weeks | Drug | Efavirenz 600 mg |
Primary outcome
Change in DEXA-measured Limb Fat Between the EFV and ATV/r Arms
Time frame: 48 weeks
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.
7 secondary outcomes
Compare Changes for DEXA-measured Limb Fat Between EFV and ATV/r Arms
Time frame: 96 weeks
Compare Changes in CD4, HIV-1 RNA Levels and Adverse Events in Two Arms
Time frame: 96 weeks
Compare Changes in Fat mtDNA, mtRNA and Fat Apoptosis Between the Two Arms
Time frame: 96 weeks
Comparing Fasting Lipid Levels Between the Two Arms
Time frame: 96 weeks
Comparing Glucose Metabolism (Fasting Insulin, QUIKI and HOMA-IR) Between the Two Arms
Time frame: 96 weeks
Compare Changes in Levels of Hs-CRP Between the Two Arms
Time frame: 96 weeks
Correlate the Changes in DEXA-measured Fat Limb With Fat mtDNA, mtRNA and Fat Apoptosis
Time frame: 96 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marisa Tungsiripat, MD principal investigator
The Cleveland Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Atazanavir/ritonavir and Efavirenz in people with HIV Infection and Mitochondrial Dysfunction, run by The Cleveland Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 11 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Aug 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in DEXA-measured Limb Fat Between the EFV and ATV/r Arms (time frame: 48 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2017.