Using a ketogenic diet to treat Alzheimer's disease

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

This study is testing whether a ketogenic diet can help people with mild to moderate Alzheimer's disease improve their thinking skills and daily living abilities.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 300 (estimated)
• Ages: 50 Years to 85 Years
• Sex: All
• Sponsor: Capital Medical University (Academic / other)
• Locations: 1 site (Beijing, Beijing)
• Trial ID: NCT06681948 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the tolerability, efficacy, and safety of a ketogenic diet (JT821) in patients with mild to moderate Alzheimer's disease. It is a randomized, double-blind, placebo-controlled study involving 300 subjects across multiple centers in China. Participants will be assigned to either the ketogenic diet group or a placebo group, with assessments of cognitive function and daily living abilities conducted at specified intervals during the treatment period. Safety evaluations will also be performed to monitor any adverse effects.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 50 to 85 with mild to moderate Alzheimer's disease who meet specific cognitive assessment criteria.

Not a fit: Patients with severe Alzheimer's disease or those who do not meet the eligibility criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve cognitive function and quality of life for patients with Alzheimer's disease.

How similar studies have performed: Previous studies have shown promise in using ketogenic diets for neurodegenerative diseases, suggesting potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Subject is between the ages of 50 - 85;
2. 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;
3. Meeting the diagnostic criteria for probable AD dementia of the National Institute on Aging and the Alzheimer's Association (NIA-AA) (2011);
4. Having experienced memory decline for at least 12 months and a slow progressive trend;
5. 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;
6. Total score on the Hachinski Ischemic Scale (HIS) ≤ 4 points;
7. Total score on the Hamilton Depression Scale (HAMD, 17-item version) ≤ 17 points;
8. 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;

   ③The grade on the Brain White Matter Lesion Rating Scale (Fazekas Scale) ≤ 2. If the patient can provide the results of the brain MRI oblique coronal hippocampal scan that meet the protocol requirements within 6 months prior to the screening visit, it can be used as the basis for enrollment and does not need to be repeated. If the researcher is unable to determine whether the subject's condition has changed, additional brain MRI plain scan and oblique coronal hippocampal scan can be conducted prior to enrollment.
9. Female patients must be postmenopausal women (postmenopause ≥ 24 weeks), have undergone surgical sterilization, or fertile women who agree to take effective contraceptive measures during the study. Fertile women or patients with a postmenopausal period shorter than 24 weeks must undergo a urine pregnancy test during the screening period, and the result must be negative;
10. Subjects are required to be receiving stable and regular anti-dementia drug treatment for more than 1 month at the first screening;
11. The subject should have a stable and reliable caregiver who can provide care for at least 4 days per week, with at least 4 hours per day. The caregiver will assist the subject throughout the study and must accompany the subject to each study visit, ensuring sufficient interaction and communication with the subject to facilitate the researcher in completing the relevant scale evaluations.
12. Prior to the screening visit examination, the subject must sign a written informed consent form. If the subject cannot sign due to limited cognitive ability or other reasons, the signature may be left blank, and the rationale must be stated. The legal guardian should provide the reason, sign the name, date, and time in the reason description area, and also sign the name, date, and time in the legal guardian column.

Exclusion Criteria:

1. 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;
2. Fasting blood glucose \> 7.0 mmol/L or patients previously diagnosed with diabetes;
3. 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;
4. 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;
5. 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;
6. Fasting triglycerides ≥ 5.7 mmol/L or total cholesterol ≥ 10.34 mmol/L at the screening visit and baseline;
7. Presence any of the following infections at the screening visit:

   Positive human immunodeficiency virus antibody (HIV Ab); Positive Treponema pallidum antibody (TP Ab);
8. 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;
9. 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;
10. Having undergone major surgeries deemed unsuitable for enrollment by the investigator within 6 months before the screening visit or those planning to undergo major surgeries during the study period (The definition of major surgeries refers to Grade 3 and Grade 4 surgeries as outlined in the "Administrative Measures for Grading of Surgeries in Medical Institutions (Trial)" implemented on December 6, 2022);
11. Patients who have suffered from malignant tumors within 3 years prior to the screening visit (excluding basal cell carcinoma of the skin that has been radically cured, squamous cell carcinoma of the skin and/or carcinoma in situ that has been radically resected);
12. Having a history of alcohol or drug abuse within 1 year prior to the screening visit;
13. Known allergy to any components of the investigational product in this study;
14. Having uncorrectable visual or auditory impairments or any other conditions that would affect the assessment of the scale;
15. Lactating women;
16. Contraindications to JT821:

Absolute contraindications:

1. Type 1 diabetes
2. Primary carnitine deficiency (Laboratory tests: Hypoglycemia with low ketone levels, elevated creatine kinase (CK), etc.)
3. Carnitine palmitoyltransferase (CPT) I and II deficiency (Laboratory tests: Hypoglycemia with low ketone levels, elevated transaminases, CK, elevated blood ammonia, tandem mass spectrometry for measurement of blood acylcarnitine profile, etc.)
4. Carnitine translocase deficiency (Laboratory tests: Hypoglycemia with low ketone levels, elevated transaminases, CK, elevated blood ammonia, tandem mass spectrometry for measurement of blood acylcarnitine profile, etc.)
5. β-Oxidation disorders (Laboratory tests: Blood glucose, electrolytes, blood lipids, coagulation, liver function, kidney function)
6. Medium-chain acyl dehydrogenase deficiency (MCAD) (Laboratory tests: Hypoglycemia with low ketone levels, elevated transaminases, CK, elevated blood ammonia, metabolic acidosis, tandem mass spectrometry for measurement of blood acylcarnitine profile, etc.)
7. Long-chain acyl dehydrogenase deficiency (LCAD) (Laboratory tests: Hypoglycemia with low ketone levels, elevated transaminases, CK, elevated creatine kinase isoenzyme (CK-MB) and lactate dehydrogenase (LDH), tandem mass spectrometry for measurement of blood acylcarnitine profile)
8. Short-chain acyl dehydrogenase deficiency (SCAD) (Laboratory tests: Tandem mass spectrometry for measurement of blood acylcarnitine profile, determination of SCAD enzyme activity)
9. Long-chain 3-hydroxyacyl-CoA deficiency (Laboratory tests: Hypoglycemia with low ketone levels, elevated transaminases, CK, elevated CK-MB and LDH, analysis of blood acylcarnitine profile, etc.)
10. Medium-chain 3-hydroxyacyl-CoA deficiency (Laboratory tests: Hypoglycemia with low ketone levels, elevated transaminases, CK, elevated CK-MB and LDH, analysis of blood acylcarnitine profile, etc.)
11. Pyruvate carboxylase deficiency (Laboratory tests: Hypoglycemia with low ketone levels, elevated transaminases, CK, elevated CK-MB and LDH, analysis of blood acylcarnitine profile, etc.)
12. Porphyria (Laboratory tests: Sunlight test of urinary porphobilinogen) Relative contraindications: (Fasting blood glucose \< 2.8 mmol/L, blood ketone \> 0.5 mmol/L) Patients who cannot maintain adequate nutrition (17) Any other situations that the investigator considers unsuitable for participating in this study; (18)Currently participating in other drug/device clinical trials.

Where this trial is running

Beijing, Beijing

• Capital Medical University Xuanwu Hospital — Beijing, Beijing, China (Recruiting)

Study contacts

• Principal investigator: Jianping Jia, Dr. — Xuanwu Hospital, Beijing
• Study coordinator: Jianping Jia, Dr.

Conditions Alzheimer Disease; Ketogenic Diet