Alzheimer Disease, Asthenia, Frailty, Sarcopenia
Conditions
Keywords
Silkworm Pupa Powder, Nutritional Status, Frailty State, Cognitive Function, Dietary Supplement
Brief summary
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
Interventions
DIETARY_SUPPLEMENTSilkworm pupa powder
Silkworm pupa powder, 2 times a day, two packets (12\*2 g) each time, take with warm water, before meals, for three months
Sponsors
Zhejiang Provincial Tongde Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to 90 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) | The 0th、 4th 、8th and 12th week after taking Silkworm | The ADAS-Cog is a tool designed to assess the severity of cognitive impairment in patients with Alzheimer's disease (AD). It consists of 12 items that evaluate multiple cognitive domains, including memory, orientation, language, praxis (practical ability), attention, and others. Through a series of standardized cognitive tasks, it measures the severity of AD-related cognitive symptoms and tracks changes in response to treatment. Higher total scores indicate more severe cognitive impairment. |
| Bilateral Hippocampal Volume | The 0th、 4th 、8th and 12th week after taking Silkworm Silkworm pupa powder | Bilateral hippocampal volume will be measured using 3.0T structural MRI T1-weighted imaging. Lower hippocampal volume indicates greater AD-related brain atrophy. |
| Entorhinal Cortex Volume | The 0th、 4th 、8th and 12th week after taking Silkworm Silkworm pupa powder | Entorhinal cortex volume will be measured using 3.0T structural MRI T1-weighted imaging. Lower volume indicates greater AD-related brain atrophy. |
| Temporoparietal Regional Volume | The 0th、 4th 、8th and 12th week after taking Silkworm Silkworm pupa powder | Temporoparietal regional volume will be measured using 3.0T structural MRI T1-weighted imaging. Lower volume indicates greater AD-related brain atrophy. |
| Cortical Thickness of AD-Related Brain Regions | The 0th、 4th 、8th and 12th week after taking Silkworm Silkworm pupa powder | Cortical thickness in AD-related brain regions, including the entorhinal cortex and temporoparietal cortex, will be measured using 3.0T structural MRI. Lower cortical thickness indicates greater cortical atrophy. |
| Fractional Anisotropy | The 0th、 4th 、8th and 12th week after taking Silkworm Silkworm pupa powder | Fractional anisotropy will be measured using diffusion tensor imaging to assess white matter microstructural integrity. Lower fractional anisotropy generally indicates reduced white matter integrity. |
| Mean Diffusivity | The 0th、 4th 、8th and 12th week after taking Silkworm Silkworm pupa powder | Mean diffusivity will be measured using diffusion tensor imaging to assess white matter microstructural changes. Higher mean diffusivity generally indicates greater microstructural disruption. |
| Radial Diffusivity | The 0th、 4th 、8th and 12th week after taking Silkworm Silkworm pupa powder | Radial diffusivity will be measured using diffusion tensor imaging to assess white matter microstructural changes. Higher radial diffusivity generally indicates greater white matter microstructural abnormality. |
| Default Mode Network Functional Connectivity | The 0th、 4th 、8th and 12th week after taking Silkworm Silkworm pupa powder | Functional connectivity of the default mode network will be assessed using resting-state functional MRI to evaluate AD-related brain network function. |
| Salience Network Functional Connectivity | The 0th、 4th 、8th and 12th week after taking Silkworm Silkworm pupa powder | Functional connectivity of the salience network will be assessed using resting-state functional MRI to evaluate AD-related brain network function. |
| Amplitude of Low-Frequency Fluctuations | The 0th、 4th 、8th and 12th week after taking Silkworm Silkworm pupa powder | Amplitude of low-frequency fluctuations will be measured using resting-state functional MRI to assess local spontaneous neuronal activity. |
| Regional Homogeneity | The 0th、 4th 、8th and 12th week after taking Silkworm Silkworm pupa powder | Regional homogeneity will be measured using resting-state functional MRI to assess local synchronization of neuronal activity. |
| Blood Neurofilament Light Chain Concentration | The 0th、 4th 、8th and 12th week after taking Silkworm Silkworm pupa powder | Neurofilament light chain concentration in blood will be measured as a biomarker of neuronal injury and neurodegeneration. Higher concentrations generally indicate greater neuronal injury. |
| Aβ42 Concentration in Blood or Cerebrospinal Fluid | The 0th、 4th 、8th and 12th week after taking Silkworm Silkworm pupa powder | Aβ42 concentration in blood or cerebrospinal fluid will be measured as an Alzheimer's disease-related amyloid biomarker. |
| Aβ40 Concentration in Blood or Cerebrospinal Fluid | The 0th、 4th 、8th and 12th week after taking Silkworm Silkworm pupa powder | Aβ40 concentration in blood or cerebrospinal fluid will be measured as an Alzheimer's disease-related amyloid biomarker. |
| Aβ42/Aβ40 Ratio in Blood or Cerebrospinal Fluid | The 0th、 4th 、8th and 12th week after taking Silkworm Silkworm pupa powder | The Aβ42/Aβ40 ratio in blood or cerebrospinal fluid will be measured as an Alzheimer's disease-related amyloid biomarker. |
| Phosphorylated Tau 181 Concentration in Blood or Cerebrospinal Fluid | The 0th、 4th 、8th and 12th week after taking Silkworm Silkworm pupa powder | Phosphorylated tau 181 concentration in blood or cerebrospinal fluid will be measured as a biomarker of tau pathology in Alzheimer's disease. |
| Phosphorylated Tau 217 Concentration in Blood or Cerebrospinal Fluid | The 0th、 4th 、8th and 12th week after taking Silkworm Silkworm pupa powder | Phosphorylated tau 217 concentration in blood or cerebrospinal fluid will be measured as a biomarker of tau pathology in Alzheimer's disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CIBIC-plus Score | The 0th、 4th 、8th and 12th week after taking Silkworm Silkworm pupa powder | The Clinician's Interview-Based Impression of Change Plus Caregiver Input is a semi-structured interview tool used to assess global clinical change in patients with dementia after treatment. The score ranges from 1 to 7, with 1 indicating very much improved, 4 indicating no change, and 7 indicating very much worsened. |
| MMSE Total Score | The 0th、 4th 、8th and 12th week after taking Silkworm Silkworm pupa powder | Mini-Mental State Examination (MMSE): A validated 30-point cognitive screening tool evaluating domains including orientation, memory, attention, language, and visuospatial abilities. Rationale: The dual assessment leverages: CIBIC-plus for holistic, clinician-judged disease progression (anchored to baseline severity). MMSE for quantifiable tracking of specific cognitive deficits. |
Countries
China
Contacts
CONTACTJiangtao Zhang
Outcome results
None listed