Silkworm Pupa Powder Improves Dementia.

A Prospective, Double-Blind, Randomized Controlled Trial Evaluating Silkworm Pupa Powder Versus Placebo in Improving Alzheimer's Disease Among Patients

The purpose of this clinical trial is to determine whether silkworm pupa powder is effective in treating Alzheimer's disease. It will also investigate whether silkworm pupa powder can improve the nutritional and frailty status of patients with Dementia. The main questions it aims to answer are:

• Will silkworm pupa powder improve the daily living conditions of patients with Alzheimer's disease?
• Will silkworm pupa powder improve the nutritional status and frailty of Alzheimer's disease patients?

Researchers will compare silkworm pupa powder with a placebo (a similar substance containing 0.5% silkworm pupa powder) to see if silkworm pupa powder can treat Alzheimer's disease.

Participants will:

• Take silkworm pupa powder or placebo daily for four months;
• Visit the clinic for check-ups and tests every four weeks;
• Record their symptoms and various physiological indicators.

Study Overview

• Status: Recruiting
• Conditions: Asthenia; Sarcopenia; Alzheimer Disease(AD)
• Intervention / Treatment: Dietary supplement: Silkworm pupa powder; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jiangtao Zhang; Phone Number: +8618969125501; Email: 18969125501@163.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310012
      • Recruiting
      • Tongde Hospital of Zhejiang Province
      • Contact: Jiangtao Zhang, Phd; Phone Number: 8618969125501; Email: 18969125501@163.com
      • Contact: Yihua Jiang, bachelor; Phone Number: 8613819189045; Email: 917547557@qq.com
      • Principal Investigator: Jiangtao Zhang, Phd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of probable Alzheimer's disease (AD) according to the National Institute on Aging-Alzheimer's Association (NIA-AA) criteria, with disease severity classified as mild, moderate, or severe (i.e., Mini-Mental State Examination [MMSE] total score between 0 and 24 points [inclusive] at 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 of age (inclusive), with at least a primary school education. Both males and females are eligible.
• 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 non-AD-related permitted 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.
• Caregiver availability: Participant has a stable and reliable caregiver, as confirmed by the investigator.
• Informed consent: 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 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. Participants with abnormal syphilis test results.
• Patients with comorbid psychiatric disorders.
• Long-term alcoholism or substance abuse that may compromise the evaluation of treatment efficacy.
• Participants with intolerance or allergy to the study medications.
• 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.

• Antibiotic use:

  1. Continuous antibiotic use for more than 10 days within 12 weeks prior to baseline.
  2. Anticipated need for antibiotic treatment exceeding 10 days during the study.
• 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.
• Participation in any clinical trial involving novel chemical entities for Alzheimer's disease (AD) within 6 months prior to screening, unless confirmed to have been in the placebo group.
• Clinically significant abnormalities in physical examination, vital signs, laboratory tests, or electrocardiogram (ECG) requiring further investigation, treatment, or posing risks to study procedures/safety.
• Participation in clinical trials involving therapeutic monoclonal antibodies, antibody-derived proteins, immunoglobulin therapy, or vaccines within 6 months prior to screening, unless confirmed to have been in the placebo group.
• Participation in clinical trials involving anti-amyloid therapies (including monoclonal antibodies or BACE inhibitors), unless confirmed to have received only placebo.
• Uncontrolled immune disorders requiring treatment with immunoglobulins, systemic monoclonal antibodies (or derivatives), systemic immunosuppressants, or plasmapheresis during the study.
• Participants with uncontrolled bleeding disorders, including platelet count <50,000 or INR >1.5 (for those not on anticoagulants, e.g., warfarin). Participants on anticoagulants must have optimized and stable dosing for ≥4 weeks prior to screening. Anticoagulated participants are excluded from cerebrospinal fluid (CSF) assessments.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control group; Placebo, 2 sachets (12*2 g) twice a day, with warm water, before meals, for three months	Dietary supplement: Placebo; Placebo, 2 sachets (12*2 g) twice a day, with warm water, before meals, for three months
Experimental: Experimental Group; Silkworm pupa powder, 2 times a day, two packets (12*2 g) each time, take with warm water, before meals, for three months	Dietary supplement: Silkworm 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog)	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.	The 0th、 4th 、8th and 12th week after taking Silkworm
Frailty indicators	This study employs serum 25-hydroxyvitamin D concentration as the central biomarker for frailty assessment. The selection is predicated on vitamin D's pivotal role in preserving musculoskeletal function and neuroprotective mechanisms, coupled with established evidence that suboptimal 25-hydroxyvitamin D levels exhibit significant correlations with geriatric frailty syndrome and cognitive decline. Through quantitative analysis via high-precision mass spectrometry, dynamic monitoring of vitamin D status alterations pre- and post-intervention will be conducted. Further investigation will elucidate its associations with frailty phenotypes (e.g., grip strength, gait speed) and dementia progression pathways.	The 0th、 4th 、8th and 12th week after taking Silkworm Silkworm pupa powder.
Frailty indicators	Plasma D-dimer concentration has been incorporated into the core biomarker panel for frailty assessment.Change in plasma D-dimer levels from baseline to 12 months, measured by immunoassay, to evaluate its association with disease progression in Alzheimer's disease	The 0th、 4th 、8th and 12th week after taking Silkworm Silkworm pupa powder.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive and Global Functional Assessment:	The combined evaluation of cognitive decline and global clinical status in Alzheimer's disease (AD) will be assessed using: Clinician's Interview-Based Impression of Change plus caregiver input (CIBIC-plus): A semi-structured clinician-rated scale capturing global changes in cognition, function, and behavior, incorporating caregiver perspectives. 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. This approach aligns with FDA guidelines for multidimensional evaluation of therapeutic efficacy in AD trials (e.g., 21 CFR 314.510). Statistical Analysis: Changes in CIBIC-plus (ordinal scale) and MMSE scores (continuous scale) will be analyzed longitudinally,	The 0th、 4th 、8th and 12th week after taking Silkworm Silkworm pupa powder.
Assessing patient nutritional improvement using Third Lumbar Skeletal Muscle Index (L3-SMI).	The nutritional index is evaluated using the Third Lumbar Skeletal Muscle Index (L3-SMI): A single cross-sectional image of L3 is obtained through CT scanning, and skeletal muscles in the image are identified and quantified using a HU threshold of -29 to 150. The total muscle area at this level is calculated using 3D Slicer software, and then divided by the square of the height (m^2) to obtain the Third Lumbar Skeletal Muscle Index (L3-SMI). Time Frame: The 0th、 4th 、8th and 12th week after taking Silkworm Silkworm pupa powder.	The 0th、 4th 、8th and 12th week after taking Silkworm Silkworm pupa powder.

Collaborators and Investigators

• Sponsor: Zhejiang Provincial Tongde Hospital
• Collaborators: Hangzhou Institute of Medicine Chinese Academy of Sciences

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: March 21, 2025
• First Submitted That Met QC Criteria: March 21, 2025
• First Posted (Actual): March 27, 2025

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: nutritional status; Alzheimer Disease; Sarcopenia; asthenia; frailty state
• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Manifestations; Mental Disorders; Pathological Conditions, Anatomical; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Muscular Atrophy; Atrophy; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Alzheimer Disease; Sarcopenia; Asthenia
• Other Study ID Numbers: Jiangtao Zhang

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No