The Ketogenic Diet in the Treatment of Alzheimer's Disease

NCT ID: NCT06681948

Last Updated: 2024-11-12

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-20
• Study Completion Date: 2025-05-30

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or if the subject or their legal guardian actively requests to withdraw or retracts informed consent, they may be withdrawn based on the investigator's determination.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.

Conditions

Alzheimer Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Ketogenic diet

The subjects initially enter the screening phase (≤ 2 weeks); following randomization, they undergo the titration period (≤ 2 weeks), gradually titrating to the maximum dose stipulated in the protocol or the maximum tolerable dose for the subject; during the treatment period (26 weeks), but if intolerance emerges during the treatment, the subject can revert to the previous tolerated dose for continued treatment.

The dosage was titrated incrementally until reaching the maximum daily dose of 30g * 3 meals/day as stipulated in the protocol or the maximum tolerable daily dose for the subject. After entering the treatment period (from week 3 to week 28), this dose was maintained for 26 weeks.

Group Type: EXPERIMENTAL

Ketogenic diet

Intervention Type: DIETARY_SUPPLEMENT

Ketogenic diet

Control

The subjects initially enter the screening phase (≤ 2 weeks); following randomization, they undergo the titration period (≤ 2 weeks), gradually titrating to the maximum dose stipulated in the protocol or the maximum tolerable dose for the subject; during the treatment period (26 weeks), but if intolerance emerges during the treatment, the subject can revert to the previous tolerated dose for continued treatment.

The dosage was titrated incrementally until reaching the maximum daily dose of 30g * 3 meals/day as stipulated in the protocol or the maximum tolerable daily dose for the subject. After entering the treatment period (from week 3 to week 28), this dose was maintained for 26 weeks.

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DIETARY_SUPPLEMENT

placebo

Interventions

Ketogenic diet

Ketogenic diet

Intervention Type: DIETARY_SUPPLEMENT

placebo

placebo

Intervention Type: DIETARY_SUPPLEMENT

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.

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

West China Hospital

OTHER

Sponsor Role: collaborator

The First Affiliated Hospital of Zhengzhou University

OTHER

Sponsor Role: collaborator

Tianjin Huanhu Hospital

OTHER

Sponsor Role: collaborator

Shandong Provincial Hospital

OTHER_GOV

Sponsor Role: collaborator

Peking University Third Hospital

OTHER

Sponsor Role: collaborator

Shanghai Mental Health Center

OTHER

Sponsor Role: collaborator

Beijing Tiantan Hospital

OTHER

Sponsor Role: collaborator

Xiangya Hospital of Central South University

OTHER

Sponsor Role: collaborator

First Affiliated Hospital of Chongqing Medical University

OTHER

Sponsor Role: collaborator

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

OTHER

Sponsor Role: collaborator

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

OTHER

Sponsor Role: collaborator

Sichuan Provincial People's Hospital

OTHER

Sponsor Role: collaborator

Brain Hospital Affiliated to Guangzhou Medical University

UNKNOWN

Sponsor Role: collaborator

Sir Run Run Shaw Hospital

OTHER

Sponsor Role: collaborator

Capital Medical University

OTHER

Sponsor Role: lead

Responsible Party

Jianping Jia

Head of Department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jianping Jia, Dr.

Role: PRINCIPAL_INVESTIGATOR

Xuanwu Hospital, Beijing

Locations

Capital Medical University Xuanwu Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Jianping Jia, Dr.

Role: CONTACT

jjp@ccmu.edu.cn

0086-10 - 83199449

Facility Contacts

Jianping Jia, Dr.

Role: primary

jjp@ccmu.edu.cn

0086-10-83199449

Other Identifiers

XWYY-GLST-01

Identifier Type: -

Identifier Source: org_study_id