HIV Infections
Conditions
Keywords
mitochondria, HIV, lipoatrophy
Brief summary
The purpose of this study is to examine the effect of rosiglitazone on limb fat and mitochondrial indices in HIV-1-infected subjects receiving stable antiretroviral therapy that does not contain stavudine (d4T) or zidovudine (AZT).
Detailed description
This is a phase II, randomized, double-blind, placebo-controlled study of rosiglitazone for the treatment of HIV-associated lipoatrophy. Subjects will receive blinded study treatment for 48 weeks. This study will examine the effect of rosiglitazone on limb fat and mitochondrial indices in HIV-1-infected subjects receiving stable antiretroviral therapy that does not contain d4T or AZT. The study also will assess the safety and tolerability of rosiglitazone in this population, and its effect on carotid IMT, prevalence of metabolic syndrome, lipid parameters and glucose metabolism.
Interventions
DRUGRosiglitazone
Rosiglitazone 4mg BID
DRUGPlacebo
Placebo for rosiglitazone
Sponsors
GlaxoSmithKline
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Lipoatrophy * Thymidine sparing ARV for at least 24 weeks * Prior thymidine NRTIs for at least 12 months
Exclusion criteria
* Diabetes * Heart failure * Liver disease * Hormonal therapies
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Limb Fat at 48 Weeks | 48 weeks | Limb fat was measured at baseline and visit week 48 using dual-energy x-ray absorptiometry (DEXA), and change from baseline to week 48 (week 48 - baseline) was estimated for the treatment groups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| the Change in the Carotid IMT of the Common Carotid Artery | 48 weeks | Carotid IMT of the Common carotid artery (CCA) was measured at baseline and week 48, and change from baseline to week 48 (week 48 - baseline) was estimated for the treatment groups. |
Countries
United States
Participant flow
Recruitment details
Recruited at Case Western Reserve University and Cleveland Clinic. Recruitment occurred between from July 2006 (first subject was randomized) to December 2007 (last subject was randomized).
Pre-assignment details
A total of 71 subjects were randomized. Results are reported for 71 subjects.
Participants by arm
| Arm | Count |
|---|---|
| Rosiglitazone Rosiglitazone 4mg daily for 4 weeks then the dose increased to 4mg twice daily for the remainder of the study (44 weeks) | 34 |
| Placebo Placebo arm | 37 |
| Total | 71 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 4 | 5 |
Baseline characteristics
| Characteristic | Rosiglitazone | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 34 Participants | 37 Participants | 71 Participants |
| Age, Continuous | 48 years STANDARD_DEVIATION 7 | 50 years STANDARD_DEVIATION 7 | 49.04 years STANDARD_DEVIATION 7 |
| CD4+ cell count | 596 cells/mm3 | 691 cells/mm3 | 645.5 cells/mm3 |
| Gender Female | 5 Participants | 7 Participants | 12 Participants |
| Gender Male | 29 Participants | 30 Participants | 59 Participants |
| Region of Enrollment United States | 34 participants | 37 participants | 71 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 34 | 7 / 37 |
| serious Total, serious adverse events | 15 / 34 | 13 / 37 |
Outcome results
Primary
Change in Limb Fat at 48 Weeks
Limb fat was measured at baseline and visit week 48 using dual-energy x-ray absorptiometry (DEXA), and change from baseline to week 48 (week 48 - baseline) was estimated for the treatment groups.
Time frame: 48 weeks
Population: Intention to treat analysis with last observation carried forward if week 48 limb fat data was missing and post-baseline limb fat was availble.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rosiglitazone | Change in Limb Fat at 48 Weeks | 448 grams |
| Placebo | Change in Limb Fat at 48 Weeks | 153 grams |
Comparison: The primary outcome measure was the change in limb fat at 48 weeks between the rosiglitazone and placebo group.p-value: 0.02Wilcoxon (Mann-Whitney)
Secondary
the Change in the Carotid IMT of the Common Carotid Artery
Carotid IMT of the Common carotid artery (CCA) was measured at baseline and week 48, and change from baseline to week 48 (week 48 - baseline) was estimated for the treatment groups.
Time frame: 48 weeks
Population: Intention to treat analysis with last observation carried forward if week 48 carotid IMT data was missing and post-baseline IMT data was available
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rosiglitazone | the Change in the Carotid IMT of the Common Carotid Artery | 0.10 mm |
| Placebo | the Change in the Carotid IMT of the Common Carotid Artery | 0.15 mm |