Effects of Treatment With Doxycycline and Rifampicin on Biomarkers of Alzheimer's Disease in the Cerebrospinal Fluid
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Clinical Dementia Rating scale
研究概览
简要总结
This study will determine if biomarkers found in the cerebrospinal fluid of people with Alzheimer's disease, are affected by treatment with two common antibiotics, doxycycline and rifampicin, suggesting a disease-modifying effect of those treatments.
详细描述
Diagnostic markers in the cerebrospinal fluid (CSF) have become a rapidly growing research field. Potential disease-modifying drugs like the antibiotics rifampicin and doxycycline, highlight the need of improved diagnostic accuracy and offer the potential to examine how these treatments may actually exert their clinical effects.
Cerebrospinal fluid biomarkers (the 42 amino acid form of β-amyloid (Aβ), total tau, and phosphorylated tau) have been evaluated in scientific studies. Tau proteins are considered "state" markers, whereas Aβ(1-42) proteins can be used as "stage" markers. These CSF markers have high sensitivity to differentiate early AD from normal aging, depression, alcohol dementia and Parkinson's disease. When these biomarkers are used in combination with a medical history, clinical examination, laboratory tests and brain imaging, the diagnostic accuracy is improved.
Matrix metalloproteinase (MMP) dysregulation is thought to contribute to a variety of pathological conditions such as arthritis, cancer, atherosclerosis, aneurysms, nephritis, tissue ulcers, and fibrosis. In addition, MMP involvement has been demonstrated in the pathogenesis of a variety of CNS disorders, including bacterial and viral disorders, stroke, multiple sclerosis, ALS, and AD.
There is an inflammatory response in AD. This includes complement activation, elevated C-reactive protein (CRP), elevated pro-inflammatory cytokines (including IL-1-β, IL-6, TNF-α, TGF-β, S100-β), chemokine alterations (IL-8, MIP-1-α, MIP-1-β, MCP-1), and microglial.
We are measuring the biochemical markers of Aβ(1-40) and Aβ(1-42), P-tau and T-tau, matrix metalloproteinases (MMP-2, MMP-9), pro-inflammatory cytokines (IL-1beta, TNF-alpha), and anti-inflammatory cytokines (IL-4 and IL-10) at the start and one year after treatment in the multi-centered, randomized, controlled, trial of disease-modifying drugs rifampicin and/or and doxycycline to slow the progress of Alzheimer's disease by affecting the production of these biomarkers.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female
- •Age greater than or equal to 50 years
- •Diagnosis of probable Alzheimer's disease by NINCDS-ADRDA criteria
- •Standardized Mini-Mental State Examination score 14-26 inclusive
- •A caregiver who consents to monitor study medications, report on patient function, bring the patient to visits, etc.
- •Vision, hearing, language ability sufficient to complete standardized testing in English.
- •Patient consents (or legal representative consents for patient)
- •Generally stable level of health where patient may be reasonably expected to complete a 1 year trial
排除标准
- •Other neurodegenerative diseases such as Lewy body or Parkinson's
- •Cognitive impairment due to: acute trauma, subdural hematoma, hypoxic cerebral damage, B12 deficiency, infections such as AIDS or meningitis, cerebral neoplasia, endocrine deficiencies, mental retardation
- •Significant cerebrovascular disease or multi-infarct dementia
- •Intra-cranial pathology such as tumour
- •Co-existing medical conditions such as epilepsy, major psychiatric conditions, depression (Cornell Depression in Dementia Scale score of 12 or more), significant liver, kidney, lung, metabolic or endocrine diseases
- •Clinically significant cardiac disease such as uncontrolled angina or hypertension
- •Anti-dementia treatments other than donepezil, galantamine, rivastigmine, memantine
- •Enrollment in trials with other investigational drugs
- •Antibiotic use more than one month in the last six months
- •Allergy to doxycycline or rifampicin
研究组 & 干预措施
2 AD Doxycycline only
Doxycycline 100 mg b.i.d. plus placebo matched to rifampin o.d. for 12 months.
干预措施: doxycycline (Drug)
1 AD combined doxycycline + rifampin
Doxycycline 100 mg b.i.d. plus rifampin 300 mg o.d. for 12 months.
干预措施: doxycycline (Drug)
1 AD combined doxycycline + rifampin
Doxycycline 100 mg b.i.d. plus rifampin 300 mg o.d. for 12 months.
干预措施: rifampicin (Drug)
2 AD Doxycycline only
Doxycycline 100 mg b.i.d. plus placebo matched to rifampin o.d. for 12 months.
干预措施: Placebo matched to Rifampin (Drug)
3 Rifampin only
Rifampin 300 mg o.d. plus placebo matched to doxycycline b.i.d. for 12 months.
干预措施: rifampicin (Drug)
3 Rifampin only
Rifampin 300 mg o.d. plus placebo matched to doxycycline b.i.d. for 12 months.
干预措施: Placebo matched to doxycycline (Drug)
4 Double Placebo
Placebo matched to Doxycycline b.i.d. plus placebo matched to rifampin o.d. for 12 months.
干预措施: Placebo matched to doxycycline (Drug)
4 Double Placebo
Placebo matched to Doxycycline b.i.d. plus placebo matched to rifampin o.d. for 12 months.
干预措施: Placebo matched to Rifampin (Drug)
结局指标
主要结局
Clinical Dementia Rating scale
时间窗: 12 months
Standardized Alzheimer's disease Assessment Scale -cognitive subscale
时间窗: 12 months
次要结局
未报告次要终点