The Ketogenic Diet in the Treatment of Behavioral Variant Frontotemporal Dementia

Prior treatment

• Having a low-carb diet , ketogenic diet, or vegan diet within 3 months before the screening visit or being currently doing.
• 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;

Other illness

• Dementia caused by other factors: Alzheimer's Disease，vascular dementia, central nervous system infections (such as AIDS, syphilis, etc.), 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 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;
• Patients diagnosed with schizophrenia spectrum disorder ,bipolar disorder, moderate to severe depression or delirium according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).
• Presence any of the following infections at the screening visit:
  • Positive human immunodeficiency virus antibody (HIV Ab); Positive Treponema pallidum antibody (TP Ab);
• Having uncorrectable visual or auditory impairments or any other conditions that would affect the assessment of the scale;
• Type 1 diabetes
• Liver failure

Lab values

• 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;
• Primary carnitine deficiency (Laboratory tests: Hypoglycemia with low ketone levels, elevated creatine kinase (CK), etc.)
• Carnitine palmitoyl transferase (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.)
• 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.)
• β-Oxidation disorders (Laboratory tests: Blood glucose, electrolytes, blood lipids, coagulation, liver function, kidney function)
• 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.)
• Very long-chain acyl dehydrogenase deficiency (VLCAD) (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)
• 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)
• Short-chain acyl dehydrogenase deficiency (SCAD) (Laboratory tests: Tandem mass spectrometry for measurement of blood acylcarnitine profile, determination of SCAD enzyme activity)
• 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.)
• 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.)
• Pyruvate carboxylase deficiency (Laboratory tests: Hypoglycemia with low ketone levels, elevated transaminases, CK, elevated CK-MB and LDH, analysis of blood acylcarnitine profile, etc.)
• Porphyria (Laboratory tests: Sunlight test of urinary porphobilinogen)
• Pregnancy
  • Relative contraindications:
  • Patients who cannot maintain adequate nutrition (Fasting blood glucose \< 2.8 mmol/L, blood ketone \> 0.5 mmol/L) (15) Any other situations that the investigator considers unsuitable for participating in this study; (16)Currently participating in other investigational product/device for treatment or participating in other clinical trials for treatment purposes.

Other

• Contraindications to JT821:
  • Absolute contraindications:
• Acute pancreatitis

• Subject is between the ages of 45 - 70;
• Meetting the diagnostic criteria for "probable bvFTD published by the International bvFTD Standards Consortium in 2011;
• Subjects must not undergo any drug adjustment treatment for 2 months prior to the enrollment and during the enrollment period ;
• Subjects must sign a written informed consent form prior to the screening visit examination. 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.
• Subject is between the ages of 45 - 70;
• Meetting the diagnostic criteria for "probable bvFTD published by the International bvFTD Standards Consortium in 2011;
• Subjects must not undergo any drug adjustment treatment for 2 months prior to the enrollment and during the enrollment period ;
• Subjects must sign a written informed consent form prior to the screening visit examination. 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.