Effects of Montelukast Therapy on Alzheimer's Disease (EMERALD)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 4
- 主要终点
- Number of Patients With Seizures
研究概览
简要总结
This is a one-year, double-blind placebo-controlled randomized clinical trial that compares montelukast to placebo in individuals with mild cognitive impairment (MCI) and early Alzheimer's disease (AD) dementia. The measures include cognitive function, cerebrospinal fluid (CSF) biomarkers and neuroimaging (cerebral perfusion and markers of vascular brain damage).
Participants will be treated with montelukast (escalating doses:10, 20 to 40 mg) or matched placebo.
详细描述
Treatment options for Alzheimer's disease (AD) remain limited, especially treatments linking neurovascular and neuroinflammatory changes with clinical manifestations of the disease. Prior research studies have documented a positive effect of cysteinyl leukotriene type 1 (cysLT-1) receptor antagonist, particularly Montelukast, on inflammatory processes in the brain and on neuronal injury, blood-brain-barrier (BBB) integrity, and amyloid-β42 (Aβ) protein accumulation. Although montelukast is currently in use for the treatment of inflammatory diseases e.g. bronchial asthma and exercise-induced bronchospasm, its effects on memory and thinking abilities and on AD biomarkers are yet to be fully understood.
This is a single site randomized controlled trial at Emory University that compares the effects of montelukast vs. placebo on memory and thinking abilities, as well as on brain imaging and markers of brain degeneration. Each participant will undergo a screening process following informed consent to determine if they meet study eligibility criteria. Participants will be enrolled in the study for 1 year.
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, Investigator)
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
- •Age: 50 years or older
- •MCI group will be defined based on:
- •(i) Subjective memory concern;
- •(ii) 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];
- •(iii) Montreal Cognitive Assessment (MoCA) < 26;
- •(iv) Clinical Dementia Rating (CDR) scale /Memory box score=0.5;
- •(v) General functional performance sufficiently preserved (Functional Assessment Questionnaire ≤5).
- •Early AD dementia group will be defined based on:
- •(i) Subjective memory concern;
- •(ii) 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];
- •(iii) Montreal Cognitive Assessment (MoCA) <26;
- •(iv) Clinical Dementia Rating scale/Memory box score 1 or 2;
- •(v) Early AD dementia defined as Functional Assessment Staging Test (FAST) of 4 or 5
排除标准
- •Intolerance to Montelukast;
- •Current diagnosis of bronchial asthma or exercise-induced bronchospasm and currently on Montelukast or other leukotriene receptor antagonists (Zafirlukast, Pranlukast);
- •Liver disease (elevated liver enzymes (>2x normal): Alanine aminotransferase (ALT), AST, alkaline phosphatase, total bilirubin);
- •Renal disease (Creatinine >2.0 mg/dl), platelets<50,000/μl, or INR>1.9;
- •Diagnosis of any neurological or psychiatric disorders that affects cognition such as uncontrolled depression, schizophrenia, Parkinson's disease or use of anti-Parkinsonian therapies (unless used for essential tremor), multiple sclerosis, or other active medical condition that in the judgment of the study physicians would affect the safety of the subject or scientific integrity of the study;
- •Other contributing factors to cognitive impairment such as uncontrolled hypothyroidism (TSH >10 mU/l) or untreated low vitamin B12 (<250 ng/mL);
- •Uncontrolled congestive heart failure reflected by poor exercise tolerance and shortness of breath at rest or with some exertion;
- •Actively undergoing chemotherapy or radiation therapy for cancer treatment;
- •History of stroke in the past 3 years;
- •Severely impaired cognition (MoCA ≤10, FAST >5 or CDR >2);
- •Inability to have MRI and LP e.g. for MRI, metal implants or cardiac pacemaker or for LP, 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. Subjects who can have either one lumbar puncture (LP) or MRI will be enrolled;
- •Inability to have cognitive assessment due to hearing, vision, or language issues or due to severe impairment;
- •History of increased intracranial pressure (ICP);
- •In those who are unable to demonstrate that they understood the details of the study using the University of California, San Diego Brief Assessment of Capacity to Consent (UBACC) instrument modified for EMERALD (i.e. lack of decisional-capacity to consent), a study partner/surrogate who can sign on their behalf will be required; otherwise, they will be excluded;
- •Use of phenobarbital or rifampin due to drug interaction.
研究组 & 干预措施
Montelukast Group
Montelukast (10, 20, or 40 mg)
干预措施: Montelukast (Drug)
Placebo Group
Matched placebo pill
干预措施: Placebo oral tablet (Drug)
结局指标
主要结局
Number of Patients With Seizures
时间窗: Baseline, 1 year
Number of participants that reported seizures during follow up time
Number of Participants With Any Gastrointestinal (GI) Symptoms
时间窗: Baseline, 1 year
Number of participants with any GI symptoms reported: diarrhea, nausea, vomiting
Number of Participants With Reported Anaphylaxis
时间窗: Baseline, 1 year
Number of participants with reported anaphylaxis during follow up time
Neuropsychiatric Inventory Questionnaire (NPI-Q) Score
时间窗: Baseline, 1 year
The NPI-Q is designed to be a self-administered questionnaire completed by informants about patients for whom they care. Each of the 12 NPI-Q domains contains a survey question that reflects cardinal symptoms of that domain. Initial responses to each domain question are "Yes" (present) or "No" (absent). If the response to the domain question is "No", the informant goes to the next question. If "Yes", the informant then rates both the Severity of the symptoms present within the last month on a 3-point scale and the associated impact of the symptom manifestations on them (i.e. Caregiver Distress) using a 5-point scale. The NPI-Q provides symptom Severity and Distress ratings for each symptom reported, and total Severity and Distress scores reflecting the sum of individual domain scores. NPI-Q Severity score range: 0-36 (lower is better).
Number of Discontinuations From Montelukast
时间窗: Baseline, 1 year
Number of participants that stopped taking Montelukast during follow up time
Number of Participants With Elevated Liver Enzymes
时间窗: Baseline, 1 year
Number of participants with elevated liver enzymes during follow up
Prothrombin Time (PT)/ International Normalized Ratio (INR)
时间窗: Baseline, 1 year
Prothrombin time (PT)/ international normalized ratio (INR) will be measured at baseline and 1 year.
次要结局
- CSF Tau Levels(Baseline, 1 year)
- CSF Amyloid(Baseline, 1 year)
- Clinical Dementia Rating (CDR) Score(Baseline, 1 year)
- NIH Toolbox Cognition Battery (NIHTB-CB)(Baseline, 1 year)
研究者
Ihab Hajjar
Associate Professor
Emory University