Minocycline in the Treatment of HIV-Associated Cognitive Impairment in Uganda
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 73
- 试验地点
- 1
- 主要终点
- 24-week Change of Uganda Neuropsychological Test Battery Summary Measure (U NP Sum)
研究概览
简要总结
Purpose: The purpose of the study is to assess the safety and effectiveness of minocycline, an antibiotic, in the treatment of Human immunodeficiency virus (HIV)-associated cognitive impairment in Uganda.
Study Design: Treatment, 24-week Randomized, Placebo-Controlled, Double-Blind Phase with Optional 24-week Open Label Phase for Subjects with a cluster of differentiation 4 (CD4) Count in the 251-350 Range
- Arm 1: Minocycline 100 mg orally every 12 hours (50 subjects)
- Arm 2: Matching placebo orally every 12 hours (50 subjects)
Primary Objective:
· To examine whether minocycline treatment will improve cognitive performance after 24 weeks compared to baseline
Secondary Objectives:
- To examine whether minocycline treatment for 24 weeks is safe and well-tolerated in individuals with HIV-associated cognitive impairment
- To examine whether minocycline treatment for 48 weeks is safe and well-tolerated in individuals with HIV-associated cognitive impairment
- To examine whether minocycline treatment for 24 weeks improves functional impairment
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •HIV infection prior to study entry
- •Naïve to any antiretroviral regimen and ineligible to receive antiretroviral therapy by cluster of differentiation 4 (CD4) criteria in Uganda
- •Negative serum or urine pregnancy test for women of childbearing potential
- •Willingness to use birth control
- •Age 18-65 years
- •AIDS Dementia Scale Stage 0.5 OR 1
- •Impaired cognitive performance as evidenced by an International HIV Dementia Scale (HDS) as defined by the protocol
- •Ability to sit or stand and swallow intact capsules with an 8-ounce glass of water
- •Ability and willingness of subject or legal guardian/ representative to give written informed consent
- •Resident within a 20km radius of Kampala city
排除标准
- •Current cancers other than basal cell carcinoma, in situ carcinoma of the cervix, or Kaposi's sarcoma without evidence of visceral involvement or which does not require systemic chemotherapy
- •Severe premorbid psychiatric illness, including schizophrenia and major depression which, in the in investigator's opinion, is likely to interfere with study compliance
- •Active symptomatic AIDS-defining opportunistic infection within 45 days prior to study entry
- •Confounding neurological disorders as defined in the protocol
- •Central nervous system infections or cancers as defined in the protocol
- •Systemic lupus
- •Thyroid disease diagnosed within 24 weeks prior to entry
- •Breastfeeding
- •Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements
- •Serious illness requiring systemic treatment and/or hospitalization until subject either completes therapy or is clinically stable on therapy, in the opinion of the investigator
- •History of allergy/sensitivity to minocycline or other tetracyclines and their formulations
- •Any other clinically significant condition or laboratory abnormality that, in the opinion of the investigator, would interfere with the subject's ability to participate in the study. This includes an individual found to have an HIV dementia scale stage 3 or
- •Any esophageal or other condition that would interfere with the swallowing of the study medication
- •Use of excluded drugs as defined by the protocol
研究组 & 干预措施
Minocycline
Minocycline 100 mg orally every 12 hours
干预措施: minocycline (Drug)
Placebo
Placebo minocycline capsules every 12 hours
干预措施: minocycline placebo capsule (Drug)
结局指标
主要结局
24-week Change of Uganda Neuropsychological Test Battery Summary Measure (U NP Sum)
时间窗: At baseline and week 24
The U NP Sum is defined as the average of z scores for 9 neuropsychological test subcomponents in the neuropsychological test battery (i.e. the average of norm-adjusted ("z") scores for Grooved Pegboard Dominant Hand, Grooved Pegboard Non-dominant Hand, Color Trails 1, Color Trails 2, Symbol Digit, WHO-UCLA Verbal Learning test Trial 5, WHO-UCLA Verbal Learning test delayed recall, Digit Span forward and Digit Span backward). The outcome is defined as U NP Sum at week 24 - U NP Sum at baseline.
次要结局
- 24-week Change of Instrumental Activities of Daily Living(At baseline and week 24)
- 24-week Change of HIV RNA Plasma Viral Loads (Log10 Transformed)(At baseline and week 24)
- 24-week Change of Center for Epidemiologic Studies Depression (CES-D) Score(At baseline and week 24)
- 24-week Change of Memorial Sloan Kettering (MSK) HIV Dementia Stage(At baseline and week 24)
- 24-week Change of Karnofsky Performance Score(At baseline and week 24)
- Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms.(Time of initial Grade ≥ 2 toxicity and/or sign and symptom event up to week 24)
- Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms(Time of first Grade ≥ 2 toxicity and/or sign and symptom event up to 48 weeks)
- 24-week Change of CD4 Cell Counts(At baseline and week 24)
- 48-week Change of CD4 Cell Counts(At baseline and week 48)