A Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase II Clinical Trial to Evaluate the Efficacy and Safety of Flos Gossypii Flavonoids Tablet in the Treatment of Mild and Moderate Alzheimer's Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 240
- 试验地点
- 19
- 主要终点
- Alzheimer's Disease Assessment Scale-Cognitive section(ADAS-cog/11)
研究概览
简要总结
In clinical trials of preclinical pharmacodynamic studies, Flos Gossypii Flavonoids Tablet has been proved to significantly improve the learning and memory ability of Alzheimer's disease model. Phase I clinical tolerance test is to observe the human body's tolerance to Flos Gossypii Flavonoids Tablet, and provide a basis for the formulation of safe and reasonable dosing regimens for phase II clinical trials. Therefore, a Phase II clinical trial is now being conducted to explore the efficacy and safety of the Flos Gossypii Flavonoids Tablet in the treatment of mild to moderate Alzheimer's disease (marinus sea deficiency/brain collateral stasis syndrome). In this study, the researchers will use a multicenter, randomized, double-blind, placebo-controlled parallel method to recruit AD patients to confirm the efficacy and safety of Flos Gossypii Flavonoids Tablet. Confirmation of drug efficacy will be observed through changes in AD patients' general cognitive and different cognitive domain functions, daily living activities, and symptom severities.
详细描述
Cotton flower is a Xinjiang Uygur ethnic medicine, and its main active ingredients are flavonoids. Studies have proved that flavonoids have strong characteristics of antioxidant stress and anti-inflammatory response. Preclinical pharmacodynamic studies on rats showed that the Flos Gossypii Flavonoids Tablet could significantly improve the learning and memory ability of AD model caused by different factors, and the mechanism may be related to its inhibition of oxidative stress and inflammatory response. A total of 57 subjects were enrolled in the Phase I tolerance clinical study. The results showed that the experimental drug may temporarily increase the three indexes of glutamic oxaloacetic transaminase, creatine kinase and lactate dehydrogenase, which can self-recovery in a short time. Combined with the safety evaluation results of phase I clinical trial, Flos Gossypii Flavonoids Tablet is a drug with high safety.
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 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 50 to 85 years old (including 50 and 85 years old), male or female;
- •Meet the diagnostic criteria of "likely ad dementia" of the National Institute on aging Alzheimer's disease association (NIA-AA) (2011);
- •The subjects are primary school graduates / graduates and above, and have the ability to complete the cognitive ability test and other tests specified in the program;
- •Memory loss lasted for at least 6 months and tended to worsen gradually;
- •Subjects with mild or moderate illness: 11 ≤ MMSE ≤ 26;
- •Total score of Clinical Dementia Rating Scale (CDR):
- •Mild dementia: CDR = 1.0; Moderate dementia: CDR = 2.0;
- •The total score of Hachinski scale(HIS) ≤ 4;
- •The total score of Hamilton Depression Scale (HAMD 17 item version) is ≤ 10;
- •There was no obvious positive sign in nervous system examination;
- •Coronal scanning of head MRI in screening stage: the MTA grade of medial temporal lobe atrophy visual assessment scale is grade 2 or higher, and the signal changes of T2 FLAIR sequence in coronal position of hippocampus. If the subject can provide the head MRI film that meets the requirements within 1 month before screening, it can be used as the basis for enrollment without repeated shooting; If the researcher cannot judge whether the subject's condition has changed, the coronal MRI scan of the head before enrollment can be added;
- •The subjects should have stable and reliable caregivers, who will take care of them at least 3 days a week and at least 2 hours a day. The caregivers will accompany the subjects to participate in the whole process of the study. Caregivers must accompany the subjects to the study visit and assist the investigator in completing the Neuropsychiatric Inventory (NPI), Alzheimer's Disease Collaborative Study-Ability of Daily Living Scale (ADCS-ADL), and Clinician Interview Based Impression of Severity (CIBIC -plus), and other scale scores;
- •Agree to participate and sign the informed consent form by the legal guardian. Due to the subject's limited cognitive ability and other reasons, the subject's signature is allowed to be left blank, and the reason is explained. In addition, the legal guardian shall sign the reason statement, and the legal guardian shall sign the informed consent;
- •Meet the criteria the traditional Chinese medicine of AD which is characterized by the syndrome of insufficient sea of marrow/cerebral collateral stasis. According to the Dementia Syndrome Classification Scale (SDSD), one of the syndromes of insufficient sea of marrow/cerebral collateral stasis can be met.
排除标准
- •During screening, MRI examination showed significant focal lesions, fulfilling one of the following conditions:
- •① There were more than 2 infarcts with diameter > 2 cm at any site;
- •② MRI examination showed that there were infarcts with arbitrary diameter in key parts (such as thalamus, hippocampus, entorhinal cortex, paraolfactory cortex, angular gyrus, cortex and other subcortical gray matter nuclei);
- •③ Fazekas scale grade of white matter lesions > 2;
- •④ There are other imaging evidences that do not support mild and moderate AD;
- •Dementia caused by other reasons: vascular dementia, central nervous system infection, Creutzfeldt Jakob disease, Huntington's disease, Parkinson's disease, Lewy body dementia, traumatic dementia, other physical and chemical factors (such as drug poisoning, alcoholism, carbon monoxide poisoning, etc.), important physical diseases (such as hepatic encephalopathy, pulmonary encephalopathy, etc.), intracranial space occupying lesions (such as subdural hematoma, brain tumor), endocrine disorders (such as thyroid disease, parathyroid disease), and vitamin B12, folic acid deficiency or any other known cause;
- •Have suffered from central nervous system diseases (including stroke, optic neuromyelitis, epilepsy, etc.);
- •Subjects who were diagnosed with psychiatric disorders according to DSM-V criteria, including schizophrenia or other mental diseases, bipolar disorder, severe depression or delirium;
- •Abnormal laboratory indexes: liver function (ALT and AST) exceeded 1.5×ULN, renal function (CR) exceeded 1.5×ULN, and creatine kinase exceeded 2×ULN;
- •Untreated hypertensive and hypotensive subjects at screening, or hypertensive subjects with uncontrolled hypertension after treatment; subjects with good blood pressure control after treatment can be determined by the investigator to be suitable for inclusion in this study;
- •Within 1 month of the screening visit, the subject has new or ongoing unstable or serious heart, lung, liver, kidney and hematopoietic diseases according to the judgment of the researcher, and does not meet the conditions for clinical research;
- •Clinically, people with significant allergic reaction history, especially drug allergy history, or known allergy to this product and its excipients;
- •Dyspepsia, esophageal reflux, gastric bleeding or peptic ulcer disease, frequent heartburn (≥ once a week) or any surgical operation that may affect drug absorption (such as partial / total gastrectomy, partial / total small bowel resection and cholecystectomy) within 6 months before screening;
- •Alcohol or drug abusers;
- •Human immunodeficiency virus antibody (ant HIV) and Treponema pallidum antibody (ant TP) are positive;
- •Those who are currently using and cannot stop using drugs for Alzheimer's disease;
- •Screening for cholinesterase inhibitors, N-methyl-D-aspartate receptor antagonists (NMDA antagonists), mental retardants, antiparkinsonian drugs and opioid analgesics taken within 1 month before the visit;
- •There are uncorrectable visual and auditory disorders, and the neuropsychological test and scale evaluation cannot be completed;
- •Female subjects with positive pregnancy test or lactation and subjects unable to take effective contraceptive measures or have family planning;
- •Participated in other clinical trials within 3 months before the screening visit;
- •There are other situations that the researcher believes are not suitable to participate in this study.
研究组 & 干预措施
Active group(low dose group)
Take 5 tablets each time (including 3 tablets of study drug and 2 tablets of placebo), 3 times a day, a total of 2.7g per day. Take it with warm water half an hour before meals.
干预措施: Flos gossypii flavonoids tablet (Drug)
Active group(high dose group)
Take 5 tablets of the study drug each time, 3 times a day, a total of 4.5g per day. Take it with warm water half an hour before meals.
干预措施: Flos gossypii flavonoids tablet (Drug)
Control group
Take 5 tablets of the control drug (placebo) each time, 3 times a day, 4.5g a day. Take it with warm water half an hour before meals.
干预措施: Flos gossypii flavonoids tablet (Drug)
结局指标
主要结局
Alzheimer's Disease Assessment Scale-Cognitive section(ADAS-cog/11)
时间窗: Change from baseline in ADAS-cog scores at Week 26
Differences between the low-dose and high-dose groups in changes in ADAS cog/11 scores (relative to baseline) at weeks 13 and 26 were compared with the placebo group. The ADAS-cog/11 measures 11 items: word recall, commands, constructional praxis, naming objects or fingers, ideational praxis, orientation, word recognition, remembering word recognition test instructions, spoken language ability, word-finding difficulty and comprehension. The total score ranges from 0 to 70, with lower scores representing milder disease.
次要结局
- Alzheimer's Disease Co-operative Study Activities of Daily Living (ADCS-ADL)(Change from baseline in ADCS-ADL scores at Week 26)
- Clinician Interview Based Impression of Severity (CIBIC-plus)(Change from baseline in CIBIC-plus scores at Week 26)
- Mini-mental State Examination (MMSE)(Change from baseline in MMSE scores at Week 26)
- Neuropsychiatric Inventory (NPI)(Change from baseline in Caregiver Stress Score on the NPI Scale at Week 26)
- Dementia syndrome classification scale (SDSD)(Change from baseline in SDSD scores at Week 26)
研究者
Jianping Jia
Director and Professor
Capital Medical University