nct06534723

Phase 3 Clinical Trial of Wujia Yizhi Granules in the Treatment of Mild-to-moderate Alzheimer's Dementia (NCT06534723)

Executive Summary

Phase 3 Clinical Trial of Wujia Yizhi Granules in the Treatment of Mild-to-moderate Alzheimer's Dementia (NCT06534723)

Executive Summary

NCT06534723 is an ongoing Phase 3, multicenter, randomized, double-blind, placebo-controlled clinical trial evaluating the safety and efficacy of Wujia Yizhi Granules, a traditional Chinese medicine (TCM) formulation, in the treatment of mild-to-moderate Alzheimer's disease dementia. Sponsored by Sichuan Jishengtang Pharmaceutical Co., Ltd., this trial represents one of the most rigorous evaluations of a traditional Chinese medicine formulation for Alzheimer's disease conducted under contemporary clinical trial standards. The study aims to enroll 570 participants and will run for approximately 2.5 years, with a primary completion date anticipated in late 2026[@wujiatrial2024].

The investigation of Wujia Yizhi Granules reflects a growing interest in integrating traditional Chinese medicine approaches into evidence-based Alzheimer's disease treatment paradigms. Traditional Chinese medicine has been used for centuries to treat cognitive impairment and age-related dementia, with historical texts describing "dementia" syndromes that bear resemblance to modern diagnostic criteria. This trial represents an effort to validate these traditional approaches using contemporary clinical trial methodology, potentially offering new therapeutic options for the millions of patients affected by Alzheimer's disease worldwide["@lin2023"].

Background and Rationale

Traditional Chinese Medicine in Neurodegenerative Disease

Traditional Chinese medicine (TCM) offers a distinct philosophical and therapeutic framework for understanding and treating disease, including neurodegenerative conditions. Unlike the single-target, molecular approach that dominates Western pharmaceutical development, TCM formulations typically contain multiple bioactive compounds that act on multiple targets simultaneously, potentially addressing the complex, multifactorial pathogenesis of Alzheimer's disease[@zhou2024].

Historical Context:

Chinese medical texts dating back thousands of years describe conditions characterized by cognitive decline, memory loss, and functional impairment in elderly individuals. Traditional formulations were developed to address these "deficiency" syndromes, with the underlying philosophy that cognitive function depends on proper functioning of specific organ systems—particularly the kidney and spleen according to TCM theory.

Philosophical Foundation:

TCM approaches to cognitive impairment are based on several key principles:

The Wujia Yizhi Granules Formulation

Wujia Yizhi Granules represents a modern pharmaceutical preparation of a traditional Chinese medicine formula. The exact composition is proprietary, but formulations of this type typically incorporate multiple herbal components chosen for their synergistic effects on cognitive function.

Theoretical Mechanism:

Based on TCM theory, Wujia Yizhi Granules operates through several mechanisms:

Scientific Investigation of TCM Mechanisms

Modern scientific research has begun to elucidate potential mechanisms through which traditional Chinese medicine formulations may benefit Alzheimer's disease[@wang2022]:

Anti-inflammatory Effects:

• Many TCM compounds demonstrate anti-inflammatory properties
• Neuroinflammation is recognized as a key contributor to Alzheimer's disease pathogenesis
• TCM formulations may reduce pro-inflammatory cytokine production and microglial activation

• Oxidative stress is elevated in Alzheimer's disease brains
• Many herbal compounds possess antioxidant properties
• May protect neurons from oxidative damage

• Some TCM compounds have shown ability to modulate amyloid-beta metabolism
• Potential effects on tau phosphorylation and aggregation
• May promote clearance of pathological proteins

• TCM compounds may protect synaptic structure and function
• May enhance neurotransmitter systems
• Could support learning and memory processes

• Some formulations support mitochondrial function
• May improve neuronal energy metabolism
• Protect against apoptosis

Clinical Trial Design

Study Overview

| Parameter | Value |
|-----------|-------|
| NCT Number | NCT06534723 |
| Phase | Phase 3 |
| Status | Recruiting |
| Sponsor | Sichuan Jishengtang Pharmaceutical Co., Ltd. |
| Enrollment | 570 participants |
| Study Type | Interventional |
| Allocation | Randomized |
| Masking | Double-blind |
| Intervention | Wujia Yizhi Granules vs. Placebo |
| Duration | 12 months treatment |
| Start Date | August 2024 |
| Primary Completion | December 2026 |

Study Design

This is a Phase 3, randomized, double-blind, placebo-controlled clinical trial designed to rigorously evaluate the efficacy and safety of Wujia Yizhi Granules in mild-to-moderate Alzheimer's disease.

Key Design Features:

Diagnostic Criteria

Inclusion Criteria:

Participants must meet all of the following criteria:

• Diagnosis: Alzheimer's disease dementia according to NIA-AA criteria
• Severity: Mild-to-moderate stage (typically MMSE 12-26, CDR 0.5-2.0)
• Age: 50-85 years
• Duration: At least 6 months since diagnosis
• TCM Pattern: Syndrome of deficiency of spleen and kidney according to TCM diagnostic criteria
• Stable Medication: Stable cholinesterase inhibitor or memantine use for ≥3 months (if applicable)
• Caregiver: Availability of reliable caregiver to supervise medication and accompany to visits

• Other Dementia: Alzheimer's disease due to other causes (vascular dementia, Lewy body dementia, frontotemporal dementia)
• Significant Psychiatric: Active major depression, psychosis, or other significant psychiatric disorder
• Neurological: History of stroke, traumatic brain injury, or other neurological disease
• Medical: Uncontrolled medical conditions (hypertension, diabetes, cardiac disease)
• Medications: Use of other TCM formulations for cognitive impairment
• Laboratory: Abnormal liver or kidney function tests

TCM Syndrome Assessment

A distinctive feature of this trial is the incorporation of TCM syndrome diagnosis into participant selection. Participants must be diagnosed with "Syndrome of Deficiency of Spleen and Kidney" according to established TCM diagnostic criteria, which may include:

Spleen Deficiency Indicators:

• Fatigue
• Poor appetite
• Loose stools
• Pale tongue with thin coating

• Back pain
• Frequent urination
• Tinnitus
• Pale or weak pulse

Outcome Measures

Primary Endpoints

The trial employs multiple primary and secondary endpoints to comprehensively evaluate efficacy:

Cognitive Endpoint:

• Change from baseline to endpoint in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog12)
• Widely validated measure of cognitive function in Alzheimer's disease trials
• Assesses memory, language, praxis, and attention

• Change from baseline to endpoint in Clinical Dementia Rating-Sum of Boxes (CDR-SB)
• Comprehensive measure of global dementia severity
• Assesses cognition, function, and behavior

Secondary Endpoints

Cognitive Measures:

• Mini-Mental State Examination (MMSE)
• Montreal Cognitive Assessment (MoCA)
• Rey Auditory Verbal Learning Test (RAVLT)

• Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL)
• Functional Activities Questionnaire (FAQ)

• Neuropsychiatric Inventory (NPI)
• Geriatric Depression Scale (GDS)

• Plasma biomarkers (potentially including Aβ, tau, and neurodegeneration markers)
• Safety laboratories

TCM-Specific Assessments

Syndrome-Related Outcomes:

• TCM syndrome severity score
• Individual symptom assessment
• Quality of life according to TCM principles

Regulatory Context

TCM in Modern Clinical Trials

The conduct of rigorously controlled clinical trials for traditional Chinese medicine formulations represents an important evolution in the integration of TCM into evidence-based medicine. This trial reflects several trends:

Standardization:

• Use of standardized, pharmaceutical-grade formulations
• Rigorous quality control of herbal ingredients
• Defined dosing regimens

• Randomized, double-blind, placebo-controlled design
• Independent ethics oversight
• Pre-registered trial protocol

• Potential for regulatory approval if trial is successful
• Integration with conventional pharmaceutical regulation
• Contribution to evidence base for TCM

International Context

While this trial is being conducted primarily in China, it contributes to a global effort to evaluate TCM approaches:

China:

• Strong government support for TCM research
• Large population of treatment-naive Alzheimer's patients
• Established TCM clinical trial infrastructure

• Growing recognition of potential TCM contributions
• Interest from international pharmaceutical companies
• Potential for global regulatory submission

Safety Considerations

Safety Monitoring

The trial includes comprehensive safety monitoring:

Adverse Event Reporting:

• Systematic collection of all adverse events
• Assessment of relationship to study medication
• Severity grading

• Regular liver function tests
• Kidney function monitoring
• Hematology parameters

• Baseline and periodic electrocardiograms
• Cardiac safety assessment

Known Safety Profile

Based on pre-clinical and earlier clinical data, Wujia Yizhi Granules is expected to have a favorable safety profile, as typical of TCM formulations. Potential considerations include:

Gastrointestinal:

• Mild gastrointestinal discomfort possible
• Generally well-tolerated

• Rare possibility of allergic reactions to herbal components
• Standard monitoring protocols in place

• Low likelihood based on composition
• Standard precautions for herbal preparations

Clinical Significance

Potential Benefits

If successful, this trial could provide:

New Therapeutic Option:

• Alternative approach for Alzheimer's disease treatment
• Particularly relevant for patients seeking complementary options
• May be acceptable to patients reluctant to use Western pharmaceuticals

• Improvement in cognitive function
• Preservation of daily activities
• Reduction in behavioral symptoms

• Some evidence suggests TCM may affect underlying disease processes
• Potential to slow progression
• Multi-target approach may address disease complexity

Addressing Unmet Need

Alzheimer's disease represents one of the most significant unmet medical needs in contemporary healthcare:

Limitations of Current Therapies:

• Cholinesterase inhibitors provide modest symptomatic benefit
• No disease-modifying therapies approved
• Significant side effects with some treatments

• Different mechanism of action
• Potentially fewer side effects
• May complement existing treatments

Integration with Conventional Care

Potential Role in Treatment Paradigm

Wujia Yizhi Granules, if approved, would likely serve as:

Adjunct Therapy:

• Complementary to cholinesterase inhibitors
• May be combined with other treatments
• Integrates with conventional care

• For patients intolerant of Western medications
• Patient preference consideration
• Cultural acceptability

• Potential use in mild cognitive impairment
• Early intervention possibility
• Maintenance treatment

Cross-References

Related Pages

• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Traditional Chinese Medicine Approaches](/treatments/traditional-chinese-medicine)
• [Mild Cognitive Impairment](/diseases/mild-cognitive-impairment)
• [Amyloid Beta](/proteins/amyloid-beta)
• [Tau Protein](/proteins/tau)
• [Clinical Trials Overview](/clinical-trials/overview)
• [Drug Development Pipeline](/clinical-trials/drug-pipeline)

External Resources

• [ClinicalTrials.gov Record](https://clinicaltrials.gov/study/NCT06534723)
• [Sichuan Jishengtang Pharmaceutical](http://www.jishengtang.com/)
• [National Center for Complementary and Integrative Health](https://www.nccih.nih.gov/)

References