Raltegravir Therapy for Women With HIV and Fat Accumulation
Phase II Study of Raltegravir as Replacement for Protease Inhibitor or Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) Based Antiretroviral Therapy in Women With Fat Accumulation
Ritonavir-boosted protease inhibitor (PI) regimens have become a backbone for treatment of people with HIV. However, adverse drug effects, particularly lipodystrophy/lipoatrophy are closely associated with these regimens. Therefore, there is a need for a drug with comparable effectiveness to the ritonavir boosted PIs without the side effects of dyslipidemia, which has been associated with elevated cholesterol and cardiovascular disease
Raltegravir is an HIV integrase inhibitor in phase III clinical development. To date there are no approved drugs that target the same stage of the HIV-1 lifecycle. However, data from studies indicate that raltegravir is generally safe and well tolerated and has strong antiretroviral activity when used in combination with licensed antiretroviral medications.
This study aims to demonstrate that patients substituting raltegravir for a PI or NNRTI based antiretroviral regimen will be associated with a 10% reduction in body fat over 24 weeks.
The study will consist of a total of 10 subject visits over a period of 48 weeks. Approximately 40 female patients will participate in this study (approximately 10 at UCLA).
研究概览
研究类型
注册 (实际的)
阶段
- 阶段2
联系人和位置
学习地点
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Ontario
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Toronto、Ontario、加拿大
- University Health Network, Toronto
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California
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Los Angeles、California、美国、90035
- UCLA CARE Center
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Massachusetts
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Boston、Massachusetts、美国、02111
- Tufts University School of Medicine
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Ohio
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Cleveland、Ohio、美国、44106
- Case School of Medicine
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Tennessee
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Nashville、Tennessee、美国、37203
- Vanderbilt University
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- HIV-1 infection as documented by any licensed ELISA test kit and confirmed by Western blot at any time prior to study entry or plasma HIV-1 RNA > 2000 on two occasions,
- Female subjects 18 years or older
- Documented central fat accumulation (defined by waist circumference of > 94 cm or a waist to hip ratio of > 0.88).
- Documented HIV RNA <50 copies/mL at screening and <400 copies/mL in the past 6 months.
- Current antiretroviral therapy with two nucleoside analogues and either a non-nucleoside analogue (nevirapine, efavirenz or TMC125) or an approved protease inhibitor. Patients on NNRTI+PI at study entry will be excluded. Study participants do not need to be on their first regimen. No changes in ART in the 12 weeks prior to screening. The nucleoside backbone must include either tenofovir or abacavir and either lamivudine or emtricitabine. Fixed dose combinations with emtricitabine or abacavir are allowed.
- For females of reproductive potential (women who have not been post-menopausal for at least 24 consecutive months, i.e., who have had menses within the preceding 24 months, or women who have not undergone surgical sterilization, specifically hysterectomy, or bilateral oophorectomy and/or tubal ligation), will need a negative serum or urine pregnancy test within 48 hours prior to entry.
- Ability and willingness of subject to provide informed consent.
Exclusion Criteria:
- Pregnancy: current or within the past 6 months or breast feeding
- Prior treatment history that would preclude the use of emtricitabine or abacavir as the nucleoside backbone during study treatment
- Current use of metformin or thiazolidinediones.
- Use of growth hormone or growth hormone releasing factor in the last 6 months before screening.
- Change or initiation of anti-hyperlipemic regimen within 3 months prior to randomization; Use of stable anti-hyperlipemic regimen during the study is allowed.
- Current use of androgen therapy.
- Intent to modify diet, exercise habits or to enroll in a weight loss intervention during the study period.
- Current or projected need to use rifampin, dilantin or phenobarbital during the 48-week study period.
Laboratory values at screening of
- ANC >500 cells/mm3
- Hemoglobin <10 gm/dl
- CrCl > 60 ml/min (estimated by Cockcroft-Gault equation)
- AST or ALT > 3 x ULN
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:随机化
- 介入模型:并行分配
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
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有源比较器:Immediate
Immediate switch of PI or NNRTI to Raltegravir
|
raltegravir
其他名称:
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有源比较器:Delayed
Continue current therapy unchanged for 24 weeks, then switch PI or NNRTI to Raltegravir
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raltegravir
其他名称:
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Baseline to 24-week Change in Visceral Adipose Tissue Volume (cm^2)
大体时间:Baseline and 24 weeks
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Adipose tissue volumes were measured via single slice L4-L5 CT scan, and volumes were calculated using cm^2, not cm^3, as is standard protocol at the Tufts University Body Composition Reading Center.
The authors acknowledge that cm^2 uses area as a surrogate for volume, but this protocol is well-accepted in our field.
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Baseline and 24 weeks
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合作者和调查者
合作者
调查人员
- 首席研究员:Judith S. Currier, M.D.、University of California, Los Angeles
- 学习椅:Grace McComsey, M.D.、Case School of Medicine
出版物和有用的链接
一般刊物
- Lake JE, McComsey GA, Hulgan TM, Wanke CA, Mangili A, Walmsley SL, Boger MS, Turner RR, McCreath HE, Currier JS. A randomized trial of Raltegravir replacement for protease inhibitor or non-nucleoside reverse transcriptase inhibitor in HIV-infected women with lipohypertrophy. AIDS Patient Care STDS. 2012 Sep;26(9):532-40. doi: 10.1089/apc.2012.0135. Epub 2012 Jul 23.
- Offor O, Utay N, Reynoso D, Somasunderam A, Currier J, Lake J. Adiponectin and the steatosis marker Chi3L1 decrease following switch to raltegravir compared to continued PI/NNRTI-based antiretroviral therapy. PLoS One. 2018 May 10;13(5):e0196395. doi: 10.1371/journal.pone.0196395. eCollection 2018.
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.
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