Silkworm Pupa Powder Improves Alzheimer's Disease

A Prospective, Single-Arm Study Evaluating Silkworm Pupa Powder in Improving Alzheimer's Disease Among Patients

The goal of this clinical trial is to learn if silkworm pupa powder works to treat Alzheimer's disease in patients. It will also learn about the safety of silkworm pupa powder, and its effect on patients' nutritional and frailty status. The main questions it aims to answer are:

• Does silkworm pupa powder improve cognitive function and daily living abilities?
• Does silkworm pupa powder improve nutritional status and frailty?
• What medical problems do participants have when taking silkworm pupa powder?

Researchers will evaluate the treatment by comparing the participants' conditions after taking the powder to their baseline conditions (a single-arm study without a placebo) to see if silkworm pupa powder works to treat Alzheimer's disease.

Participants will:

• Take silkworm pupa powder every day for 12 weeks
• Visit the clinic once every 4 weeks for checkups and tests
• Use an electronic punch-card system daily and report any symptoms

Inclusion Criteria:

• Diagnosis of probable Alzheimer's disease (AD) according to the National Institute on Aging-Alzheimer's Association (NIA-AA) criteria. Disease severity is classified as mild to moderate, defined as a Mini-Mental State Examination (MMSE) total score of 0-24 points, inclusive, at both screening and baseline.
• Confirmation of AD pathology per the 2024 revised AD diagnostic criteria (biomarker-defined AD with both Aβ and tau positivity):
• Aβ positivity: Plasma Aβ42/40 ratio ≤0.08 or amyloid-PET positivity (SUVR ≥1.1).
• Tau positivity: Plasma p-tau217 ≥2.5 pg/mL (or CSF p-tau181/Aβ42 ratio ≥0.02).
• Age 50 to 90 years (inclusive), male or female, with at least a primary school education.
• Stable medication use: If receiving approved AD therapies (e.g., acetylcholinesterase inhibitors, GV-971, NMDA receptor antagonists), doses must remain stable for ≥12 weeks prior to baseline. Treatment-naïve participants are also eligible. All other permitted non-AD related concomitant medications must remain stable for ≥4 weeks prior to baseline unless otherwise specified.
• Hachinski Ischemia Scale (HIS) total score ≤4.
• Geriatric Depression Scale-15 (GDS-15) total score ≤4.
• Neuroimaging evidence: Screening CT/MRI showing age-related brain changes or cerebral atrophy.
• Participant has a stable and reliable caregiver, as confirmed by the investigator.
• Written informed consent must be provided by the participant or, if the participant lacks decision-making capacity, by a legally authorized representative (in accordance with local laws, regulations, and customs). Participants must agree to provide peripheral blood, stool, and urine samples during the study for biomarker analysis.

Exclusion Criteria:

• Diagnosis of dementia other than Alzheimer's disease (AD) or other central nervous system disorders.
• Unstable vital signs accompanied by abnormalities in cardiac, pulmonary, hepatic, renal, or other organ functions.
• Abnormally low folate and/or vitamin B12 levels, or evidence that hypothyroidism has caused or exacerbated the participant's dementia. Abnormal syphilis test results.
• Comorbid psychiatric disorders.
• Long-term alcoholism or substance abuse that may compromise the evaluation of treatment efficacy.
• Intolerance or allergy to the study medication (silkworm pupa powder).
• Abnormalities detected on cranial MRI, including ischemic or hemorrhagic infarctions, hydrocephalus, or brain tumors.
• Diagnosis of clinically significant cardiovascular or cerebrovascular disease requiring treatment within 12 months or at present.
• Geriatric Depression Scale-15 (GDS-15) score >4 at screening.
• Any other inadequately controlled condition (e.g., cardiac, respiratory, renal, or gastrointestinal disorders affecting absorption, such as gastric cancer, gastric bypass surgery, or recurrent diarrhea) that may jeopardize participant safety or interfere with study assessments, as judged by the investigator.
• Administration of any new chemical entity in an AD clinical study within 6 months prior to screening.
• Clinically significant abnormalities in physical examination, vital signs, laboratory tests, or electrocardiogram (ECG) requiring further investigation, treatment, or posing risks to study procedures or safety.
• Participation in a clinical study involving therapeutic monoclonal antibodies, antibody-derived proteins, immunoglobulin therapy, or vaccines within 6 months prior to screening.
• Participation in a clinical study involving any anti-amyloid therapies (including any monoclonal antibody therapy and any BACE inhibitor therapy).
• Any inadequately controlled immune disorder, or immune disease requiring treatment with immunoglobulins, systemic monoclonal antibodies (or derivatives), systemic immunosuppressants, or plasmapheresis during the study.
• Inadequately controlled bleeding disorders (including platelet count <50,000 or INR >1.5 for participants not on anticoagulants, e.g., warfarin). Participants on anticoagulants must have their anticoagulation status optimized and receive a stable dose within 4 weeks prior to screening. Participants receiving anticoagulant therapy must not participate in cerebrospinal fluid (CSF) assessments.
• Participation in another concurrent silkworm pupa powder intervention study conducted at the same study center.