Candesartan's Effects on Alzheimer's Disease And Related Biomarkers
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 77
- 试验地点
- 2
- 主要终点
- Number of Participants With Hypotensive Episodes and Symptoms
研究概览
简要总结
This study is intended to investigate the safety of candesartan, a blood pressure medication, in non-hypertensive individuals who have mild cognitive impairment (MCI) due to Alzheimer's disease and its effect on disease biomarkers.
详细描述
This is a double-blind placebo-control randomized clinical trial that compares candesartan to placebo in individuals with mild cognitive impairment (MCI) who also have positive Alzheimer's Disease (AD) biomarkers. The investigators will assess if blocking the effect of Ang II using angiotensin receptor blockers (ARBs) is safe in non hypertensive MCI individuals and whether the use of candesartan will be associated with changes in cerebrospinal fluid disease biomarkers.
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
- 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
- •Mild Cognitive Impairment, defined by:
- •Subjective memory concern
- •Abnormal memory function documented using the Logical Memory subscale (Delayed Paragraph Recall, Paragraph A only) from the Wechsler Memory Scale-Revised (the maximum score is 25): [<11 for 16 or more years of education; <9 for 8-15 years of education; <6 for <7 years of education]
- •Montreal Cognitive Assessment (MoCA) < 26
- •Clinical Dementia Rating scale /Memory sum Box score=0.5
- •General functional performance sufficiently preserved (Functional Assessment Questionnaire<9)
- •Amyloid positivity determined by measuring the amyloid content in the brain. This can be determined by either cerebrospinal fluid (CSF) amyloid level or an amyloid scan (PIB-PET)
排除标准
- •Intolerance to ARBs
- •Current use of ARBs, angiotensin-converting enzyme inhibitors (ACEIs) (use of antihypertensive medications other than ACEI or ARBs for other indications is allowed)
- •Current diagnosis of hypertension or current use of antihypertensive medication that is prescribed specifically for hypertensive therapy
- •SBP less than 110 or DBP less than 40 mm Hg
- •Renal disease (Creatinine >2.0 mg/dl), hyperkalemia (K>5.5 meq/dl), platelets<50,000/μl, or international normalized ratio (INR)>1.9
- •Active medical or psychiatric diseases that in the judgment of the investigator would affect the safety of the subject or scientific integrity of the study
- •Uncontrolled congestive heart failure reflected by poor exercise tolerance and shortness of breath
- •History of stroke in the past 3 years
- •Inability to have MRI (eg metal implants or cardiac pacemaker) with an exception for those who cannot have an MRI, if all other parts of the study are obtained successfully they may still be enrolled in the study, or cognitive assessment or inability to assess amyloid positivity (no lumbar puncture and no amyloid scan)
- •History of increased intracranial pressure (ICP) or bleeding diathesis (from disease states or from use of anticoagulants such as warfarin, heparin and related products, rivaroxaban or Xarelto, apixaban or Eliquis, edoxaban or Savaysa, dabigatran or Pradaxa)
- •Women of childbearing potential (non-menopausal)
- •In those who are unable to demonstrate that they understood the details of the study (ie lack of decisional-capacity to consent), a study partner/surrogate who can sign on their behalf will be required, otherwise they will be excluded
- •Current use of Lithium, as candesartan may increase lithium concentration to toxic levels
研究组 & 干预措施
Candesartan
Candesartan will be given orally once a day in a stepwise manner as follows: All participants will be initiated on 8 mg candesartan. The dose will be increased in 2 week increments to 16 mg and 32 mg as long as the systolic blood pressure (SBP) >100 mm Hg, diastolic blood pressure (DBP) >40 mm Hg and participant reports no symptoms of hypotension (dizziness or weakness). The highest achievable dose will be the Maximal Tolerated Dose (MTD) and the participant will receive this dose for the remaining duration of the study (participants will be treated for 1 year).
干预措施: Candesartan (Drug)
Placebo
Participants will receive a matched placebo once a day orally for 12 months.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With Hypotensive Episodes and Symptoms
时间窗: Up to Month 12
The number of participants with reported episodes hypotension as well as symptoms of hypotension.
Number of Participants Discontinuing Study Medication
时间窗: Up to Month 12
The number of participants who discontinued the study medication is presented here.
Number of Participants With a Hypotensive Episode
时间窗: Up to Month 12
Hypotension is defined as blood pressure \<100/40 mm Hg. Blood pressure was measured according to the American Heart Association guidelines with the subject in the sitting position and rested for 5 minutes. An appropriate cuff size (covering 60% of upper arm length and 80% of arm circumference) was used and correct cuff placement (1-2 inches above the brachial pulse on bare arm) was ensured.
Number of Participants With Symptoms of Hypotension
时间窗: Up to Month 12
Participants were asked to report any symptoms of hypotension (dizziness, weakness, fatigue and lightheadedness). All participants were given a telephone number to reach physician 24-hours per day to report symptoms they experience. The number of participants reporting symptoms of hypotension is reported here.
Number of Participants With Elevated Serum Creatinine
时间窗: Up to Month 12
The levels of creatinine were obtained from blood samples. Elevated serum creatinine is defined as levels \>2.5 milligram per deciliter (mg/dL). Elevated serum creatinine is indicative of decreased renal function.
Number of Participants With Hyperkalemia
时间窗: Up to Month 12
The levels of potassium were obtained from blood samples. Hyperkalemia is defined as potassium levels \>5.9 milliequivalent per deciliter (meq/dL). Hyperkalemia is an indication of kidney dysfunction.
次要结局
- Hippocampal Volume(Baseline, Month 12)
- Cerebrospinal Fluid (CSF) Total Tau Levels(Baseline, Month 12)
- Cerebrospinal Fluid (CSF) Amyloid Aβ42 Levels(Baseline, Month 12)
- Global Standardized Uptake Value Ratio (SUVR) of [18F]T807(Baseline, 12 Months)
- Global Standardized Uptake Value Ratio (SUVR) of (11)C-Pittsburgh Compound B ((11)C-PiB)(Baseline, 12 Months)
- EXecutive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (EXAMINER) Toolbox Composite Score(Baseline, Month 6, Month 12)
- Trail Making Test (TMT) Part B - A(Baseline, Month 6, Month 12)
- Cerebrospinal Fluid (CSF) of Tau Phosphorylated at Threonine 181 (p-tau181) Levels(Baseline, Month 12)
- Cerebrospinal Fluid (CSF) Amyloid Aβ40 Levels(Baseline, Month 12)
- Cerebrospinal Fluid (CSF) Amyloid Aβ42/Aβ40 Levels(Baseline, Month 12)
- Pulse Wave Velocity (PWV)(Baseline, Month 12)
- Augmentation Index (AI)(Baseline, Month 12)
- Vasoreactivity(Month 12)
- Clinical Dementia Rating (CDR) Score(Baseline, Month 12)
- Hopkins Verbal Learning Test (HVLT) Delayed Recall Score(Baseline, Month 6, Month 12)
- Trail Making Test (TMT) Part B(Baseline, Month 6, Month 12)
研究者
Ihab Hajjar
Associate Professor
Emory University