The Ketogenic Diet in the Treatment of Alzheimer's Disease

NCT06681948 | Completed

• 1 other identifier: XWYY-GLST-01
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Alzheimer Disease

Keywords

Ketogenic Diet; Alzheimer Disease

Outcome Measures

Primary Outcomes (1)

• Alzheimer's Disease Assessment Scale-Cognitive section(ADAS-cog)

  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.

  The comparison of the baseline change values between the experimental group and the control group after 26 weeks of treatment .

Secondary Outcomes (6)

• 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

Study Arms (2)

Ketogenic diet

EXPERIMENTAL

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.

Dietary Supplement: Ketogenic diet

Control

PLACEBO COMPARATOR

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.

Dietary Supplement: placebo

Interventions

Ketogenic diet DIETARY_SUPPLEMENT

Ketogenic diet

Ketogenic diet

placebo DIETARY_SUPPLEMENT

placebo

Control

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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.
• 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;
• Subjects are required to be receiving stable and regular anti-dementia drug treatment for more than 1 month at the first screening;
• 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.
• 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.

You may not qualify if:

• 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;
• 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);
• 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);
• Having a history of alcohol or drug abuse within 1 year prior to the screening visit;
• Known allergy to any components of the investigational product in this study;
• Having uncorrectable visual or auditory impairments or any other conditions that would affect the assessment of the scale;

Sponsors & Collaborators

• Capital Medical University: lead
• West China Hospital: collaborator
• The First Affiliated Hospital of Zhengzhou University: collaborator
• Tianjin Huanhu Hospital: collaborator
• Shandong Provincial Hospital: collaborator
• Peking University Third Hospital: collaborator
• Shanghai Mental Health Center: collaborator
• Beijing Tiantan Hospital: collaborator
• Xiangya Hospital of Central South University: collaborator
• First Affiliated Hospital of Chongqing Medical University: collaborator
• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: collaborator
• The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School: collaborator
• Sichuan Provincial People's Hospital: collaborator
• Brain Hospital Affiliated to Guangzhou Medical University: collaborator
• Sir Run Run Shaw Hospital: collaborator

Study Sites (1)

Capital Medical University Xuanwu Hospital

Beijing, Beijing Municipality, 100053, China

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Diet, Ketogenic

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Diet, Carbohydrate-Restricted; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Jianping Jia, Dr.

  Xuanwu Hospital, Beijing

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Department

Study Record Dates

• First Submitted: October 20, 2024
• First Posted: November 12, 2024
• Study Start: February 23, 2024
• Primary Completion: September 10, 2025
• Study Completion: November 11, 2025
• Last Updated: March 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)