HIV-Associated Lipodystrophy SyndromePhase 4NCT00135356
Study of Reyataz in HIV-infected Patients With Lipodystrophy Syndrome
A Phase 4 study testing Atazanavir (ATV) + ritonavir (RTV), continuation of backbone 2 nucleoside reverse transcriptase inhibitor (NRTIs) and continuation of current HAART (boosted protease inhibitor [PI] combination + 2 NRTIs) in people with HIV-Associated Lipodystrophy Syndrome, run by Bristol-Myers Squibb at 30 sites in 9 countries.
Trial summary
The purpose of this clinical research study is to learn if human immunodeficiency virus (HIV)-infected subjects with abdominal fat accumulation on their highly active antiretroviral treatment (HAART) regimen have better changes in fat distribution after switching to atazanavir-ritonavir than those remaining on their… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV-Associated Lipodystrophy Syndrome
- What is being tested?
- Atazanavir (ATV) + ritonavir (RTV), continuation of backbone 2 nucleoside reverse transcriptase inhibitor (NRTIs) and continuation of current HAART (boosted protease inhibitor [PI] combination + 2 NRTIs)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 219 participants
- Where
- 30 sitesin 9 countries
- Study dates
- Jul 2005to Jun 2008
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV-1 infected on HAART regimen containing 2 NRTI and boosted PI for at least 12 weeks prior to screening. Subjects may not have experienced virological failure to more than one prior PI-containing regimen. Must be able to swallow tablets
- Viral load <400 c/mL at screening and stable for at least 6 months
- Signs of fat redistribution and lipohypertrophy (abdominal) Waist to Hip Ratio >0.90 and Waist Circumference >88.2 cm for men and Waist Circumference >75.3 for women
Who cannot join
- Pregnant or breastfeeding women
- New HIV-related opportunistic infections
- Active alcohol or substance use
- Grade 4 lab toxicity
- History of taking atazanavir (ATV)
- Prohibited therapies, including non-nucleoside reverse transcriptase inhibitors (NNRTI)
Trial locations and contacts
30 sites in 9 countries.
30 sites in 9 countries
Spain6 sites
Local Institution
Barcelona
Local Institution
Elche (Alicante)
Local Institution
Guipuzcoa
Local Institution
Madrid
Local Institution
Málaga
Local Institution
Valencia
France5 sites
Local Institution
Bondy
Local Institution
Lagny-sur-Marne
Local Institution
Lyon
Local Institution
Nice
Local Institution
Paris
United States4 sites
Local Institution
Fort Lauderdale, Florida
Local Institution
Honolulu, Hawaii
Local Institution
Houston, Texas
Local Institution
Huntersville, North Carolina
Italy4 sites
Local Institution
Brescia
Local Institution
Milan
Local Institution
Modena
Local Institution
Roma
Mexico3 sites
Local Institution
Guadalajara, Jalisco
Local Institution
Puebla City
Local Institution
Zapopan, Jalisco
Canada2 sites
Local Institution
Ottawa, Ontario
Local Institution
Toronto, Ontario
United Kingdom2 sites
Local Institution
Brighton, East Sussex
Local Institution
London, Greater London
About this study
Official title: A Phase IV, Open-Label, Randomized, Multicenter Trial Assessing a Reyataz-Based Substitution Approach in the Management of Lipodystrophy Syndrome. Research Into Atazanavir in Lipodystrophy (The REAL Study)
The purpose of this clinical research study is to learn if human immunodeficiency virus (HIV)-infected subjects with abdominal fat accumulation on their highly active antiretroviral treatment (HAART) regimen have better changes in fat distribution after switching to atazanavir-ritonavir than those remaining on their current protease inhibitor boosted HAART regimen.
- Conditions
- HIV-Associated Lipodystrophy Syndrome
- Being tested
- Atazanavir (ATV) + ritonavir (RTV), continuation of backbone 2 nucleoside reverse transcriptase inhibitor (NRTIs), continuation of current HAART (boosted protease inhibitor [PI] combination + 2 NRTIs)
- Keywords
- HIV infections
- Medical subject headings
- HIV-Associated Lipodystrophy Syndrome, HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Atazanavir (ATV) + ritonavir (RTV), continuation of backbone 2 nucleoside reverse transcriptase inhibitor (NRTIs)Drug
Also called Reyataz
Capsules, Oral, ATV 300 mg + RTV 100 mg once daily up to 96 weeks
continuation of current HAART (boosted protease inhibitor [PI] combination + 2 NRTIs)Drug
Protease inhibitor [PI] combination + 2 NRTIs
| Study group | Role | What they receive |
|---|---|---|
| Switch arm | Active comparator | Not described Receives: Drug: Atazanavir (ATV) + ritonavir (RTV), continuation of backbone 2 nucleoside reverse transcriptase inhibitor (NRTIs) |
| Control Arm | Active comparator | Not described Receives: Drug: continuation of current HAART (boosted protease inhibitor [PI] combination + 2 NRTIs) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Trunk-to-limb Fat Ratio as Measured by Dual Energy X-Ray Absortiometry (DEXA) at Week 48
Mean changes from Baseline in trunk-to-limb fat ratio as measured by DEXA, an x-ray scan used to measure bone mineral density. Clinical improvement is associated with a decrease in values. (Baseline trunk-to-limb fat ratio values can be found in the Baseline Characteristics section.)
Measured: Baseline, Week 48
Secondary outcomes (17)
Change From Baseline in Trunk-to-limb Fat Ratio as Measured by DEXA at Week 96
Mean changes from baseline in trunk-to-limb fat ratio as measured by DEXA, an x-ray scan used to measure bone mineral density. Clinical improvement is associated with a decrease in values.(Baseline trunk-to-limb fat ratio values can be found in the Baseline Characteristics section.)
Measured: Baseline, Week 96
Mean Percent Change From Baseline in Visceral Adipose Tissue (VAT) Area by Computed Tomography (CT) Scans and in Trunk Fat by DEXA.
The mean percent change from baseline in physical signs of lipohypertrophy, as assessed objectively by changes in visceral adipose tissue (VAT) area (cm2) by computed tomography (CT) scans and by changes in trunk fat (kg) by DEXA. Clinical improvement is associated with a decrease in values. (Baseline values can be found in the Baseline Characteristics section.)
Measured: Baseline, Week 48, Week 96
Mean Percent Change From Baseline in Peripheral Adipose Tissue (Limb Fat) by DEXA and by Changes in Subcutaneous Adipose Tissue (SAT) Area by CT Scans
The mean percent change from baseline in physical signs of lipoatrophy, as assessed objectively by changes in peripheral adipose tissue (ie, limb fat (kg) by DEXA and in subcutaneous adipose tissue (SAT) area by CT scans. Clinical improvement is associated with stable values, or an increase in values. (Baseline values can be found in the Baseline Characteristics section.)
Measured: Baseline, Week 48, Week 96
Mean Percent Change From Baseline in Total Body Fat by DEXA and in Total Adipose Tissue (TAT) Area by CT Scans
The mean percent change from baseline in total body fat by DEXA and in total adipose tissue (TAT) area by CT scans. Total body fat and TAT are both associated many factors (trunk fat + limb fat + other [weight, etc]), and thus clinical improvement cannot be predicted based solely an increase or decrease of these values. (Baseline values can be found in the Baseline Characteristics section.)
Measured: Baseline, Week 48, Week 96
Mean Percent Changes From Baseline in Fasting Lipids
Mean percent changes from baseline in fasting total, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and non-HDL cholesterol, triglycerides, and apolipoprotein B
Measured: Baseline, Week 48, Week 96
Mean Changes From Baseline in Fasting Glucose at Week 48 and Week 96
Measured: Baseline, Week 48, Week 96
Mean Changes From Baseline in Fasting Insulin at Week 48 and Week 96
Measured: Baseline, Week 48, Week 96
Mean Changes From Baseline in Fasting Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)
HOMA-IR is an index used in evaluation of obese patients at risk for type 2 diabetes which requires fasting glucose and insulin concentrations. It is a mathematical model based on the theory of a negative feedback loop between the liver and β-cells that regulates both fasting glucose and insulin concentrations and can be used to estimate pancreatic β-cell function and degree of insulin resistance. HOMA-IR normal values are between 2 and 2.5. HOMA-IR ≥ 2.5 indicates insulin-resistance.
Measured: Baseline, Week 48, Week 96
Mean Changes From Baseline in Body Weight at Week 48 and Week 96
Measured: Baseline, Week 48, Week 96
Mean Changes From Baseline in Waist Circumference at Week 48 and Week 96
Measured: Baseline, Week 48, Week 96
Mean Changes From Baseline in Body Mass Index at Week 48 and Week 96
Measured: Baseline, Week 48, Week 96
Mean Changes From Baseline in Waist-to-Hip Ratio at Week 48 and Week 96
Mean changes from baseline in proportion of waist to hip measurements.
Measured: Baseline, Week 48, Week 96
Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and AEs Leading to Discontinuation
Percentage of Participants with AEs, Serious AEs (SAEs), Deaths, and AEs leading to discontinuation. An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a cancer, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event.
Measured: Through Week 96 of study therapy
Percentage of Participants With Abnormal Liver Function Tests
Percentage of participants with Abnormal Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Total Bilirubin (TBILI) measurements. Values for liver tests are graded using the modified World Health Organization (WHO) criteria. Grade 1 is mild, grade 2 is moderate, grade 3 is severe, grade 4 is life threatening or disabling.
Measured: Week 48, Week 96
Percentage of Participants With Adverse Events (AEs) Leading to Discontinuation
Percentage of Participants with AEs leading to discontinuation of study therapy. An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. All events listed in this table were SAEs, except for renal impairment and hypertriglycerideamia, which were an AEs (and did not meet the 5 percent threshold reported in Adverse Event module of this record).
Measured: Through Week 96
Kaplan-Meier Cumulative Proportion of Participants Without Virologic Rebound (HIV RNA ≥400 c/mL) at Timepoints up to Week 96 in Treated Participants With HIV RNA <400 c/mL at Baseline
Virologic rebound was measured from the first dose of study therapy to the first of the 2 consecutive measurements ≥400 c/mL. Time to virologic rebound was analyzed using life tables. Measured Values show the Kaplan-Meier cumulative proportion of participants without virologic rebound up to the end of the respective interval.
Measured: Weeks 8-12, Weeks 20-24, Weeks 32-36, Weeks 44-48, Weeks 56-60, Weeks 68-72, Weeks 80-84, Weeks 92-96
Mean Change From Baseline in CD4 Count
Mean change from baseline in CD4 count among treated subjects
Measured: Baseline, Week 48, Week 96
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2005 (estimated)
- Study startJul 2005
- Primary completionJul 2007
- Study completionJun 2008
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-Associated Lipodystrophy SyndromeStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 219 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00135356
- Sponsor's protocol ID
- AI424-131
- Status last verified
- Apr 2010
- First submitted
- 25 Aug 2005
- Last updated
- 7 May 2010
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IV, Open-Label, Randomized, Multicenter Trial Assessing a Reyataz-Based Substitution Approach in the Management of Lipodystrophy Syndrome. Research Into Atazanavir in Lipodystrophy (The REAL Study)
- ClinicalTrials.gov ID
- NCT00135356
- Acronym / sponsor ID
- AI424-131
- Conditions
- HIV-Associated Lipodystrophy Syndrome
- Keywords
- HIV infections
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 219 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Study start
- Jul 2005
- Primary completion
- Jul 2007 (actual)
- Study completion
- Jun 2008 (actual)
- First posted
- 26 Aug 2005 (estimated)
- Results
- Posted 7 May 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this clinical research study is to learn if human immunodeficiency virus (HIV)-infected subjects with abdominal fat accumulation on their highly active antiretroviral treatment (HAART) regimen have better changes in fat distribution after switching to atazanavir-ritonavir than those remaining on their current protease inhibitor boosted HAART regimen.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Switch arm | Active comparator | Drug: Atazanavir (ATV) + ritonavir (RTV), continuation of backbone 2 nucleoside reverse transcriptase inhibitor (NRTIs) |
| Control Arm | Active comparator | Drug: continuation of current HAART (boosted protease inhibitor [PI] combination + 2 NRTIs) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- HIV-1 infected on HAART regimen containing 2 NRTI and boosted PI for at least 12 weeks prior to screening. Subjects may not have experienced virological failure to more than one prior PI-containing regimen. Must be able to swallow tablets
- Viral load <400 c/mL at screening and stable for at least 6 months
- Signs of fat redistribution and lipohypertrophy (abdominal) Waist to Hip Ratio >0.90 and Waist Circumference >88.2 cm for men and Waist Circumference >75.3 for women
Key exclusion criteria (6 listed)
- Pregnant or breastfeeding women
- New HIV-related opportunistic infections
- Active alcohol or substance use
- Grade 4 lab toxicity
- History of taking atazanavir (ATV)
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 (ATV) + ritonavir (RTV), continuation of backbone 2 nucleoside reverse transcriptase inhibitor (NRTIs)Also: ReyatazCapsules, Oral, ATV 300 mg + RTV 100 mg once daily up to 96 weeks | Drug | Switch arm |
| continuation of current HAART (boosted protease inhibitor [PI] combination + 2 NRTIs)Protease inhibitor [PI] combination + 2 NRTIs | Drug | Control Arm |
Primary outcome
Change From Baseline in Trunk-to-limb Fat Ratio as Measured by Dual Energy X-Ray Absortiometry (DEXA) at Week 48
Time frame: Baseline, Week 48
Mean changes from Baseline in trunk-to-limb fat ratio as measured by DEXA, an x-ray scan used to measure bone mineral density. Clinical improvement is associated with a decrease in values. (Baseline trunk-to-limb fat ratio values can be found in the Baseline Characteristics section.)
17 secondary outcomes
Change From Baseline in Trunk-to-limb Fat Ratio as Measured by DEXA at Week 96
Time frame: Baseline, Week 96
Mean Percent Change From Baseline in Visceral Adipose Tissue (VAT) Area by Computed Tomography (CT) Scans and in Trunk Fat by DEXA.
Time frame: Baseline, Week 48, Week 96
Mean Percent Change From Baseline in Peripheral Adipose Tissue (Limb Fat) by DEXA and by Changes in Subcutaneous Adipose Tissue (SAT) Area by CT Scans
Time frame: Baseline, Week 48, Week 96
Mean Percent Change From Baseline in Total Body Fat by DEXA and in Total Adipose Tissue (TAT) Area by CT Scans
Time frame: Baseline, Week 48, Week 96
Mean Percent Changes From Baseline in Fasting Lipids
Time frame: Baseline, Week 48, Week 96
Mean Changes From Baseline in Fasting Glucose at Week 48 and Week 96
Time frame: Baseline, Week 48, Week 96
Mean Changes From Baseline in Fasting Insulin at Week 48 and Week 96
Time frame: Baseline, Week 48, Week 96
Mean Changes From Baseline in Fasting Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)
Time frame: Baseline, Week 48, Week 96
Mean Changes From Baseline in Body Weight at Week 48 and Week 96
Time frame: Baseline, Week 48, Week 96
Mean Changes From Baseline in Waist Circumference at Week 48 and Week 96
Time frame: Baseline, Week 48, Week 96
Mean Changes From Baseline in Body Mass Index at Week 48 and Week 96
Time frame: Baseline, Week 48, Week 96
Mean Changes From Baseline in Waist-to-Hip Ratio at Week 48 and Week 96
Time frame: Baseline, Week 48, Week 96
Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and AEs Leading to Discontinuation
Time frame: Through Week 96 of study therapy
Percentage of Participants With Abnormal Liver Function Tests
Time frame: Week 48, Week 96
Percentage of Participants With Adverse Events (AEs) Leading to Discontinuation
Time frame: Through Week 96
Kaplan-Meier Cumulative Proportion of Participants Without Virologic Rebound (HIV RNA ≥400 c/mL) at Timepoints up to Week 96 in Treated Participants With HIV RNA <400 c/mL at Baseline
Time frame: Weeks 8-12, Weeks 20-24, Weeks 32-36, Weeks 44-48, Weeks 56-60, Weeks 68-72, Weeks 80-84, Weeks 92-96
Mean Change From Baseline in CD4 Count
Time frame: Baseline, Week 48, Week 96
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2010.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
30 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Atazanavir (ATV) + ritonavir (RTV), continuation of backbone 2 nucleoside reverse transcriptase inhibitor (NRTIs) and continuation of current HAART (boosted protease inhibitor [PI] combination + 2 NRTIs) in people with HIV-Associated Lipodystrophy Syndrome, run by Bristol-Myers Squibb at 30 sites in 9 countries.
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 3 inclusion and 6 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: finished, as of the sponsor's last update on 7 May 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in Spain, France, United States, Italy, Mexico and 4 more countries. 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 7 May 2010). 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 From Baseline in Trunk-to-limb Fat Ratio as Measured by Dual Energy X-Ray Absortiometry (DEXA) at Week 48 (time frame: Baseline, Week 48). 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 7 May 2010.