A Randomized, Double-Blind, Placebo Parallel-Controlled, Multicenter Clinical Study for Evaluating the Efficacy, Safety and Tolerability of JT821 in the Treatment of Mild and Moderate Alzheimer's Disease
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Alzheimer Disease
- Sponsor
- Capital Medical University
- Enrollment
- 32
- Locations
- 1
- Primary Endpoint
- Alzheimer's Disease Assessment Scale-Cognitive section(ADAS-cog)
- Status
- Completed
- Last Updated
- last month
Overview
Brief Summary
This research is a randomized, double-blind, placebo-parallel controlled, and multi-center clinical study in China, aiming to evaluate the tolerability, efficacy, and safety of JT821 (Ketogenic Diet) in the treatment of mild to moderate Alzheimer's disease.
The ketogenic diet (KD) is a low-carbohydrate, adequate protein and high-fat diet. KD was shown to be effective in treating different neurodegenerative diseases.
Detailed Description
This is a randomized, double-blind, placebo-controlled, multi-center clinical study planned to include 300 subjects diagnosed with mild to moderate Alzheimer's disease. The primary aim of the study is to evaluate the tolerability, efficacy, and safety of JT821 in the treatment of mild to moderate Alzheimer's disease. Eligible patients will be randomly assigned in a 1:1 ratio to either the JT821 group or the placebo group. All subjects will undergo a 2-week product titration period based on a stable and regular anti-dementia drug treatment before entering a 26 week treatment period. Efficacy assessments will be conducted at week 13 and week 26 during the treatment period, utilizing the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) and the Mini-Mental State Examination (MMSE) to assesses the overall cognitive function of the subjects. Additionally, the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) will evaluate daily living abilities; and the Quality of Life in Alzheimer's Disease (QOL-AD) will assess the quality of life of Alzheimer's disease patients. Safety evaluation will include the vital signs, laboratory tests (twelve-lead electrocardiogram, fasting blood glucose, blood ketone levels (β-hydroxybutyrate), urinalysis, complete blood count, fasting lipid profile, liver and kidney function), as well as the recording of any adverse events. Subjects may withdraw from the study at any time. If subjects experience a serious adverse event, become pregnant, are lost to follow-up, show poor adherence, or if the subject or their legal guardian actively requests to withdraw or retracts informed consent, they may be withdrawn based on the investigator's determination. The sponsor reserves the right to terminate the study at any time for special reasons (such as major safety concerns, force majeure, etc.). A safety follow-up will be conducted two weeks after the termination of treatment.
Investigators
Jianping Jia
Head of Department
Xuanwu Hospital, Beijing
Eligibility Criteria
Inclusion Criteria
- •Subject is between the ages of 50 - 85;
- •Subject must have completed the sixth grade of primary school (or its equivalent) and capable of completing the cognitive ability assessments and other tests as stipulated in the protocol;
- •Meeting the diagnostic criteria for probable AD dementia of the National Institute on Aging and the Alzheimer's Association (NIA-AA) (2011);
- •Having experienced memory decline for at least 12 months and a slow progressive trend;
- •Subject with mild to moderate disease severity, specifically those who meet the following criteria at the screening visit and baseline: 11 points ≤ Mini-Mental State Examination (MMSE) total score \< 26 points (for subjects with primary school education, 11 points ≤ MMSE total score ≤ 22 points); 1 point ≤ Clinical Dementia Rating Scale (CDR) total score ≤ 2 points;
- •Total score on the Hachinski Ischemic Scale (HIS) ≤ 4 points;
- •Total score on the Hamilton Depression Scale (HAMD, 17-item version) ≤ 17 points;
- •At the screening visit or within the past 6 months, subject must undergo a brain magnetic resonance imaging (MRI) plain scan and oblique coronal hippocampal scan:
- •①Showing high likelihood of AD (Visual Rating Scale of Medial Temporal Lobe Atrophy \[MTA Scale\] grade: Grade 1 or higher is considered abnormal);
- •②No infarct lesions in key areas such as the thalamus, hippocampus, entorhinal cortex, parahippocampal cortex, angular gyrus, cortex, and other subcortical gray matter nuclei;
Exclusion Criteria
- •Dementia caused by other factors: vascular dementia, central nervous system infections (such as AIDS, syphilis, etc.), Creutzfeldt-Jakob disease, Huntington's disease and Parkinson's disease, Lewy body dementia, traumatic brain injury dementia, other physical and chemical factors (such as drug poisoning, alcohol poisoning, carbon monoxide poisoning, etc.), significant somatic diseases (such as hepatic encephalopathy, pulmonary encephalopathy, etc.), intracranial space-occupying lesions (such as subdural hematoma, brain tumors), endocrine system disorders (such as thyroid diseases, parathyroid diseases) and dementia caused by vitamin deficiency or any other known causes;
- •Fasting blood glucose \> 7.0 mmol/L or patients previously diagnosed with diabetes;
- •Having suffered from neurological diseases other than Alzheimer's disease, including cerebrovascular diseases, neurodegenerative diseases, central nervous system infections, demyelinating diseases, movement disorders, epilepsy, spinal cord diseases, peripheral neuropathy, autonomic nervous system diseases, neuromuscular junction and muscle diseases;
- •Patients diagnosed with psychiatric conditions according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), including schizophrenia or other mental illnesses, bipolar disorder, moderate to severe depression or delirium;
- •Abnormal laboratory tests at screening visit and baseline: including liver function tests (alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\]) exceeding twice the upper limit of normal; and renal function (creatinine \[Cr\]) exceeding 1.5 times the upper limit of normal. Slight exceedances that are not clinically significance, as judged by the investigator, may not be excluded;
- •Fasting triglycerides ≥ 5.7 mmol/L or total cholesterol ≥ 10.34 mmol/L at the screening visit and baseline;
- •Presence any of the following infections at the screening visit:
- •Positive human immunodeficiency virus antibody (HIV Ab); Positive Treponema pallidum antibody (TP Ab);
- •Other active and poorly controlled systemic severe bacterial, viral, fungal or parasitic infections (excluding fungal nail infections) that the investigator deems unsuitable for participation in this clinical study, such as sepsis, pyemia, bacteremia, and pneumonia caused by novel coronavirus infection;
- •Gastrointestinal diseases that could affect the absorption or metabolism of the investigational product as judged by the investigator, within 2 months before the screening visit;
Outcomes
Primary Outcomes
Alzheimer's Disease Assessment Scale-Cognitive section(ADAS-cog)
Time Frame: The comparison of the baseline change values between the experimental group and the control group after 26 weeks of treatment .
The comparison of the change values from the baseline of ADAS-cog between the experimental group and the control group after 26 weeks of treatment. ADAS-cog assesses seven aspects of cognitive function: word recall, instructions, structural practice, naming, conceptual practice, orientation, and word recognition. The total score ranges from 0 to 70, with lower scores representing milder disease.
Secondary Outcomes
- Alzheimer's Disease Assessment Scale-Cognitive section(ADAS-cog)(The variations relative to the baseline in the experimental group and the control group after 13 weeks of treatment.)
- Comparison of the variations in blood ketone values relative to baseline in both groups during the treatment period(During the 26-week treatment course of the experimental group and the control group.)
- Alzheimer's Disease Co-operative Study Activities of Daily Living (ADCS-ADL)(Changes relative to baseline in both groups after 13 weeks and 26 weeks of treatment .)
- Therapeutic efficacy (evaluated by ADAS-cog) of the Ketogenic Diet (JT821) combined with different drugs after 13 and 26 weeks of treatment(The changes relative to the baseline in both groups after 13 weeks and 26 weeks of treatment.)
- Mini-Mental State Examination (MMSE)(Changes relative to baseline in both groups after 13 weeks and 26 weeks of treatment)
- Quality of Life Alzheimer's Disease（QOL-AD）(Changes relative to baseline in both groups after 13 weeks and 26 weeks of treatment.)