Montelukast Therapy on Alzheimer's Disease
关键词
抽象
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 and will be compensated for their participation.
日期
最后验证: | 08/31/2019 |
首次提交: | 06/17/2019 |
提交的预估入学人数: | 06/17/2019 |
首次发布: | 06/18/2019 |
上次提交的更新: | 09/26/2019 |
最近更新发布: | 09/29/2019 |
实际学习开始日期: | 09/24/2019 |
预计主要完成日期: | 07/31/2021 |
预计完成日期: | 07/31/2021 |
状况或疾病
干预/治疗
Drug: Montelukast Group
Drug: Placebo Group
相
手臂组
臂 | 干预/治疗 |
---|---|
Experimental: Montelukast Group Montelukast (10, 20, or 40 mg) | Drug: Montelukast Group Participants in this arm will take a pill of Montelukast daily on escalating doses: 10, 20 to 40 mg.
All participants will be initiated on 10 mg. The dose will be increased in 2-week increments to 20 mg and 40 mg as long as participants report no intolerable symptoms or adverse events. |
Placebo Comparator: Placebo Group Matched placebo pill | Drug: Placebo Group Participants in this arm will take a matched placebo pill daily |
资格标准
有资格学习的年龄 | 50 Years 至 50 Years |
有资格学习的性别 | All |
接受健康志愿者 | 是 |
标准 | Inclusion Criteria: 1. Age: 50 years or older 2. 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 scale /Memory box score=0.5; (v) General functional performance sufficiently preserved (Functional Assessment Questionnaire ≤5). 3. 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 Exclusion Criteria: 1. Intolerance to Montelukast; 2. Current diagnosis of bronchial asthma or exercise-induced bronchospasm and currently on Montelukast or other leukotriene receptor antagonists (Zafirlukast, Pranlukast); 3. Liver disease (elevated liver enzymes (>2x normal): Alanine aminotransferase (ALT), AST, alkaline phosphatase, total bilirubin); 4. Renal disease (Creatinine >2.0 mg/dl), platelets<50,000/μl, or INR>1.9; 5. 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; 6. Other contributing factors to cognitive impairment such as uncontrolled hypothyroidism (TSH >10 mU/l) or untreated low vitamin B12 (<250 ng/mL); 7. Uncontrolled congestive heart failure reflected by poor exercise tolerance and shortness of breath at rest or with some exertion; 8. Actively undergoing chemotherapy or radiation therapy for cancer treatment; 9. History of stroke in the past 3 years; 10. Severely impaired cognition (MoCA ≤10, FAST >5 or CDR >2); 11. 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, Dabigatraban or Pradaxa. Subjects who can have either one lumbar puncture (LP) or MRI will be enrolled; 12. Inability to have cognitive assessment due to hearing, vision, or language issues or due to severe impairment; 13. History of increased intracranial pressure (ICP); 14. 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; 15. Use of phenobarbital or rifampin due to drug interaction. |
结果
主要结果指标
1. Number of participants with any gastrointestinal (GI) symptoms [1 year]
2. Number of participants with reported anaphylaxis [1 year]
3. Number of participants with elevated liver enzymes [1 year]
4. Change in prothrombin time (PT)/ international normalized ratio (INR) [Baseline, 1 year]
5. Change in Neuropsychiatric Inventory Questionnaire (NPI-Q) [Baseline, 1 year]
6. Number of patients with seizures [1 year]
7. Number of discontinuations from Montelukast [1 year]
次要成果指标
1. Change in CSF amyloid [Baseline, 1 year]
2. Change in CSF tau [Baseline, 1 year]
3. Change in Clinical Dementia Rating (CDR) [Baseline, 1 year]
4. Change in NIH Toolbox Cognition battery (NIHTB-CB) [Baseline, 1 year]