Phase II, Randomized, Placebo-Controlled, Double-Blind Study of Minocycline in the Treatment of HIV-Associated Cognitive Impairment
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 107
- 试验地点
- 16
- 主要终点
- Change in Cognitive Performance Compared to Baseline
研究概览
简要总结
The purpose of this study is to determine the effectiveness of minocycline, an antibiotic, in lessening the decreased mental function sometimes caused by anti-HIV drugs.
详细描述
Cognitive impairment, including disabling cognitive, behavioral, and social dysfunction, continues to be a major problem faced by HIV-infected people taking antiretroviral therapy (ART). Research is needed to develop treatment that can be given alongside ART to prevent or lessen cognitive impairment caused by ART. Minocycline, an antibiotic commonly used for the treatment of acne and rheumatoid arthritis, has demonstrated anti-inflammatory and neuroprotective properties in previous studies. This study will evaluate the effectiveness of 24-week therapy with minocycline in lessening the cognitive impairment of HIV infected adults taking ART.
This study will last at least 24 weeks and has two steps. Patients will be stratified by HIV viral load and their neurocognitive state at study screening. In Step I, patients will be randomly assigned to one of two groups. Group 1 participants will receive twice-daily minocycline for 24 weeks; Group 2 participants will receive placebo. At the end of Phase I, study participants will be offered to enter Step II; all participants in Step II will receive twice-daily minocycline for an additional 24 weeks.
There will be a total of 8 study visits: 5 visits for Step I (including the entry visit) and 3 visits for Step II. Medical history will occur at all visits. Blood collection will occur at all visits. Participants who have positive nonreactive rapid plasma regain (RPR) values at screening will have mandatory lumbar punctures; for those with negative serum RPR results lumbar punctures are optional. Participants who test positive for syphilis will also have a lumbar puncture at their discretion to determine if syphilis has affected the brain. A neurological exam, other neuropsychological, dementia, and depression scale assessments, and urine collection will occur at most visits. Patients will be asked to complete a questionnaire on daily living at study entry and Weeks 12 and 24. Patients who have a lumbar puncture at Week 24 will receive a phone call 2 to 5 days after the procedure to report any adverse effects. Some participants may also have an electrocardiogram (ECG) during the study. For participants not on atazanavir some procedures and sample collections are optional.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Care Provider)
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 infected
- •Currently on a stable ART regimen for at least 16 consecutive weeks prior to study entry. Participants whose regimens have changed with respect to dose or formulation are eligible, but patients who have changed to different drugs in the same class are not eligible. Participants taking atazanavir must also be taking ritonavir or a ritonavir-boosted drug to be eligible for this study. More information on this criterion can be found in the protocol.
- •Plan to stay on current ART regimen between study screening and Week 24
- •AIDS Dementia Scale (ADC) Stage greater than 0
- •Cognitive impairment, as evidenced by neuropsychological tests administered at screening
- •Progressive neurocognitive decline. More information on this criterion can be found in the protocol.
- •Estimated premorbid IQ of 70 or higher indicated by an age-corrected scaled score of 5 or higher on the vocabulary section of the Wechsler Adult Intelligence Scale Revised (WAIS-R) administered at study screening
- •Karnofsky performance score of 60 or higher
- •Ability to sit and stand for at least 2 hours and swallow medications with an 8-ounce glass of water
- •Willing to use acceptable methods of contraception
- •Willing to adhere to study schedule
排除标准
- •Current cancers. Patients with basal cell carcinoma, in situ carcinoma of the cervix, or Kaposi's sarcoma without evidence of visceral involvement or cancer not requiring systemic chemotherapy are not excluded.
- •Severe premorbid psychiatric illness, including schizophrenia and major depression, which, in the opinion of the investigator, may interfere with the study
- •Active symptomatic AIDS-defining opportunistic infection within 45 days prior to study entry
- •Previous or current confounding neurological disorders. More information on this criterion can be found in the protocol.
- •Central nervous system infections or cancers. More information on this criterion can be found in the protocol.
- •Systemic lupus
- •Thyroid disease diagnosed within 24 weeks of study entry
- •Active drug or alcohol abuse that, in the opinion of the investigator, may interfere with the study
- •Serious illness requiring systemic treatment or hospitalization. Patients who complete therapy or are clinically stable on therapy are not excluded.
- •Investigational agents within 45 days prior to study entry. Patients taking expanded access drugs or drugs used in an ACTG protocol for HIV treatment or for HIV-associated complications that are not prohibited by this protocol are not excluded.
- •History of allergy/sensitivity to minocycline or other tetracyclines and their formulations
- •Any esophageal or other condition that would interfere with a patient's ability to swallow study medication
- •Participation in a previous clinical drug research trial of HIV-associated cognitive impairment. Patients who have had an objective decline in performance as defined by the protocol are not excluded.
- •Any other clinically significant condition or laboratory abnormality that, in the opinion of the investigator, would interfere with the study
- •Certain medications
- •Certain abnormal laboratory values. Patients who test positive on nonreactive rapid plasma reagin tests (RPR)are not excluded.
- •Inability to undergo lumbar punctures
- •Breastfeeding
研究组 & 干预措施
Arm 2: Matching placebo
orally every 12 hours
干预措施: Placebo (Tetracycline) (Drug)
Arm 1: Minocycline
100 mg orally every 12 hours
干预措施: Minocycline (Drug)
结局指标
主要结局
Change in Cognitive Performance Compared to Baseline
时间窗: At baseline and week 24
Th cognitive performance is measured by NPZ-8. NPZ-8 is defined as the average of age and education adjusted z-scores of eight neuropsychological tests subcomponents in the neuropsychological test battery. These eight tests are: 1. Grooved Pegboard Dominant Hand (GPD) 2. Grooved Pegboard Non-dominant hand (GPN) 3. Choice Reaction Time (CRT) 4. Sequential Reaction Time (QRT) 5. Timed Gait (TIG) 6. Trail Making Part A (TMA) 7. Trail Making Part B (TMB) 8. Symbol Digit (SYD) The primary outcome is NPZ-8 score at week24 - NPZ-8 score at baseline.
次要结局
- Change in Global Deficit Z-Score (GDS)(At baseline and week 24)
- Change in Investigator's Clinical Global Impression Score (ICGIS)(At week 24)
- Change in Cognitive Gross Motor Function Domain Z-Score(At baseline and week 24)
- Change in Fine Motor Function Domain Z-Score(At baseline and week 24)
- Change in Psychomotor Function Domain Z-Score(At baseline and week 24)
- Change in Fine Motor/Nonverbal Function Domain Z-Score(At baseline and week 24)
- Change in Information Processing Function Domain Z-Score(At baseline and week 24)
- Change in Verbal Memory Domain Z-Score(At baseline and week 24)
- Change in Frontal Systems Function Domain Z-Score(At baseline and week 24)
- Change in Karnofsky Performance Score(At baseline and week 24)
- Changes in Cluster of Differentiation 4 (CD4) Cell Counts (24 Weeks)(At baseline and weeks 24)
- Changes in Cluster of Differentiation 8 (CD8) Cell Counts (24 Weeks)(At baseline and week 24)
- Number of Participants With Grade 2 or Higher Toxicity and/or Signs and Symptoms(Throughout study up to week 48)
- Change of HIV Plasma RiboNucleic Acid (RNA) Viral Load(At baseline and week 24)
- Changes in Instrumental Activities of Daily Living Questionnaire(At baseline and week 24)
- Changes in Medication Management Test (Modified)(At baseline and weeks 24)
- Changes in Protein Markers of Oxidative Stress (Unit = Counts Per Second Only)(At pre-entry and Week 24)
- Changes in Markers of Oxidative Stress and Immune Activation (Unit=pg/mL Only)(At pre-entry and Week 24)
- Changes in Markers of Oxidative Stress (Unit = Pixels/mm2 Only)(At pre-entry and Week 24)
- Changes in Neurotransmitter Levels (Unit = uM Only)(At pre-entry and Week 24)
- Changes in Alternate Psychomotor Function Z-Score(At baseline and week 24)
- Changes in Alternate Verbal Memory Z-Score(At baseline and week 24)
- Changes in Alternate Frontal Systems Z-Score(At baseline and week 24)