Phase II Trial of Tesamorelin for Cognition in Aging HIV-Infected Persons
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 73
- 试验地点
- 4
- 主要终点
- Change in Neurocognitive Performance
研究概览
简要总结
The aim of this study is to test whether tesamorelin, in combination with a text-messaging application to help with motivation and adherence, will significantly improve memory and thinking in HIV.
详细描述
HIV infection can result in memory and thinking difficulties in some people, even those successfully treated with antiretroviral medications. Tesamorelin is an injectable medication already approved by the U.S. FDA to treat abdominal fat accumulation in HIV. Abdominal fat accumulation is linked to memory and thinking difficulties, and previous studies have suggested that tesamorelin also may be beneficial for memory and thinking, but this has not been tested in HIV. The aim of this study is to test whether tesamorelin, in combination with a text-messaging application to help with motivation and adherence, will significantly improve memory and thinking in HIV. We plan to enroll 100 volunteers with HIV infection at 2 sites - the University of California, San Diego and the University of Southern California, University of San Francisco and the satellite site, PalmTree Clinical Research, Inc. Before entry, volunteers will be required to show evidence of abdominal obesity and a minimum level of memory and thinking difficulties on cognitive tests. This is a randomized trial in which each volunteer will have a 60% chance of initially receiving tesamorelin (the immediate group) and a 40% chance of initially receiving no treatment (the deferred group). Subsequently, the deferred group (those who initially received no treatment) will receive tesamorelin for 6 months and those who initially received tesamorelin will receive no treatment for 6 months. Volunteers will be trained in the use of a 2-way text-messaging system that will help the research team to support volunteers' ability to take the study medication as directed. We will measure volunteers' memory and thinking skills before and at the end of treatment. We will collect blood at various points during the study to check for safety of the treatment and to determine its effects on the body. Volunteers will also be asked to have magnetic resonance scans of the head and abdomen to monitor the effects of the study medication on brain chemistry and abdominal fat.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •HIV-1 infection documented by any FDA licensed clinical test including HIV enzyme/antigen test or chemiluminescence immunoassay (E/CIA) or plasma HIV-1 RNA viral load.
- •Antiretroviral therapy: Patient currently receiving a combination antiretroviral therapy (cART) regimen ≥12 weeks with no interruptions longer than 7 days and HIV <500 copies/ml during that time.
- •Men or women 40 years of age and older
- •Abdominal minimal waist circumference ≥ 95cm for men and ≥94cm for women or minimal waist to hip ratio of ≥ 0.88 for women (each based on an average of three separate measurements)
- •Screening neuropsychological Global Deficit Score of ≥ 0.35
- •The following laboratory values obtained within 90 days prior to entry by any CLIA certified laboratory.
- •Absolute neutrophil count (ANC) ≥750/mm3
- •Hemoglobin ≥8.0 g/dL
- •Platelet count ≥50,000/mm3
- •HgbA1C ≤8.0%
- •Calculated creatinine clearance of ≥20 mL/min as estimated by the Cockroft-Gault formula
- •Aspartate aminotransferase (AST) (SGOT), alanine aminotransferase (ALT) (SGPT) <5 X upper limit of normal (ULN) and alkaline phosphatase <3 X upper limit of normal (ULN) without evidence of active liver disease other than non-alcoholic fatty liver disease (NAFLD) or hepatitis C requiring treatment.
- •Total bilirubin ≤2.5 x ULN (if the participant is receiving atazanavir, a total bilirubin of ≤5 x ULN is acceptable).
- •For females of reproductive potential, negative serum or urine pregnancy test within 30 days prior to entry by any test performed by a CLIA certified laboratory or is using a point of care (POC)/ CLIA-waived test.
- •Contraception requirements: For females of reproductive potential, she or male partner is willing to use a contraceptive during sexual intercourse.
- •Ability and willingness of participant or legal guardian/representative to provide informed consent
排除标准
- •Clinical contraindications
- •History of neurocognitive confounding conditions that explain current impairment including but not limited to stroke, head injury, psychotic disorder, active substance use disorder by DSM, or opportunistic CNS infection
- •Hepatitis C virus infection defined as HCV antibody positive requiring treatment and plans for treatment during study therapy
- •Active or relapsing autoimmune disorder that may require immunotherapy during this treatment trial
- •Active malignancy other than basal or squamous skin cancer.
- •Breastfeeding or pregnancy
- •Excluded medications used within the last 90 days: active or planned use of rhGH, anabolic steroids (other than replacement doses of testosterone), anti-TNFa therapy or other biologic (tocilizumab, Xelijanz, etc.)
- •Anticipated need to start new daily anti-inflammatory therapy such as NSAIDs (excluding aspirin for vascular prophylaxis), systemic corticosteroids, or anti-malarials, or plan to discontinue regular dosing with these drugs during study treatment.
- •Known allergy/sensitivity or any hypersensitivity to tesamorelin
- •Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements
- •Acute or serious illness requiring systemic treatment and/or hospitalization within 60 days prior to entry
- •Use of tesamorelin in the last 6 months
研究组 & 干预措施
Immediate group
1.4mg of tesamorelin is injected once a day for 6 months, then no treatment is given for 6 months
干预措施: Tesamorelin (Drug)
Deferred group
No treatment is given for 6 months, then 1.4mg of tesamorelin is injected once a day for 6 months
干预措施: Tesamorelin (Drug)
结局指标
主要结局
Change in Neurocognitive Performance
时间窗: Baseline and week 24
The primary outcome was neurocognitive (NC) change, measured by the summary regression-based change score (sRCS), derived from a comprehensive battery assessing seven NC domains using the Global Deficit Score (GDS). The sRCS is calculated as a z-score from regression model residuals between baseline and week 24, adjusting for practice effects, statistical artifacts, and demographics. Altogether, 15 individual z scores are computed, by dividing the difference between predicted (Xp) and obtained (Xo) follow-up scaled scores by the error term of the regression model (Xo-Xp/SD-residual) and then averaged to generate the sRCS. Scores center around 0 (no change), with negative scores indicating decline and positive scores improvement. Significant changes are defined by 90% confidence intervals (±1.645 SD) such that participants in the top 5% of the sRCS distribution of the normative, stable reference sample were defined as "improved," and the bottom 5% were defined the "decliners."
次要结局
- Insulin-like Growth Factor 1 (IGF-1)(Baseline and week 24)
研究者
Ronald Ellis
Professor of Neurosciences
University of California, San Diego