Efficacy and Safety of Yangxue Qingnao Pills in the Treatment of Mild to Moderate Alzheimer's Disease

NCT04780399 | Unknown Phase 2 DMC

• 1 other identifier: P2020-03-BDY-12-V02
• Study Type: interventional
• Target: 216
• Locations: 1 country
• Sites: 1

Brief Summary

As a traditional Chinese medicine compound, Yangxue Qingnao Pills is proven to have beneficial effects on learning and memory ability in animal models of Alzheimer's disease(AD). The purpose of the study is to evaluate the efficacy and safety of Yangxue Qingnao Pills on patients with mild to moderate AD. This phase II randomized, double-blind, parallel controlled trial include a 2 weeks run-in period, and a 48 weeks double-blind treatment period of after randomization. Participants will be randomly allocated to Yangxue Qingnao pills high dose group (7.5 g per time,2 times per day) ; and Yangxue Qingnao pills low dose group (5 g per time,2 times per day), or placebo group. The outcome measures include general cognitive function, ability of daily living, and behavioural and psychological symptoms in AD patients.

Conditions

Alzheimer Disease; Yangxue Qingnao Pills; Randomized

Outcome Measures

Primary Outcomes (2)

• Alzheimer's Disease Assessment Scale- Cognition Subscale (ADAS-cog)

  The Alzheimer's Disease Assessment Scale-Cognitive Subscale test is one of the most frequently used tests to measure cognition in research studies and clinical trials for new drugs and other interventions.The ADAS-Cog consists of 11 parts and takes approximately 30 minutes to administer.The test administrator adds up points for the errors in each task of the ADAS-Cog for a total score ranging from 0 to 70. The greater the dysfunction, the greater the score. A score of 70 represents the most severe impairment and 0 represents the least impairment.

  Change from baseline ADAS-cog score at Week 48

• Clinical dementia rating scale-sum box(CDR-SB)

  The Clinical Dementia Rating Scale (CDR) is a global assessment instrument that yields global and Sum of Boxes (CDR-SB) scores, with the global score regularly used in clinical and research settings to stage dementia severity. The CDR-SB score is obtained by summing each of the domain box scores, with scores ranging from 0 to 18. Higher score means severe global cognition impairment.

  Change from baseline CDR-SB score at Week 48

Secondary Outcomes (3)

• Mini-Mental State Examination(MMSE)

  Change from baseline MMSE score at Week 48

• Neuropsychiatric Inventory(NPI)

  Change from baseline NPI score at Week 48

• Alzheimer's Disease Cooperative Study-Activities of Daily Living scale (ADCS-ADL/23)

  Change from baseline ADCS-ADL/23 score at Week 48

Other Outcomes (2)

• Blood biomarkers including Aβ42, Aβ40, T-tau, P-tau181, NfL, TOM1, IL-1R1,IL-1b, IL-6, IL-8, TNF-a, FB, FH, sCR1, MCP-1, eotaxin-1, Ach, ChEI

  Change from baseline of Aβ42, Aβ40, T-tau, P-tau181, NfL, TOM1, IL-1R1,IL-1b, IL-6, IL-8, TNF-a, FB, FH, sCR1, MCP-1, eotaxin-1, Ach, ChEI at Week 48

• Hippocampus volume with MRI

  Change of hippocampus volume with MRI after 48 weeks'treatment from baseline

Study Arms (3)

Yangxue Qingnao pills high dose group

EXPERIMENTAL

Yangxue Qingnao pills 7.5 g per time,2 times per day.

Drug: Yangxue Qingnao pills

Yangxue Qingnao pills lower dose group

EXPERIMENTAL

Yangxue Qingnao pills 5 g per time,2 times per day, and placebo identified to Yangxue Qingnao pills 2.5 g per time, 2 times per day.

Drug: Yangxue Qingnao pills

Placebo group

PLACEBO COMPARATOR

Placebo identified to Yangxue Qingnao pills 7.5 g per time,2 times per day

Drug: Placebo

Interventions

Yangxue Qingnao pills DRUG

72 subjects in the Yangxue Qingnao pills group take 7.5g of Yangxue Qingnao pills each time, twice a day, 0.5 hours after breakfast and dinner, taking with warm water.

Yangxue Qingnao pills high dose group

Placebo DRUG

72 subjects in the placebo group take 7.5g placebo identified to Yangxue Qingnao pills each time, twice a day, 0.5 hours after breakfast and dinner, taking with warm water.

Placebo group

Eligibility Criteria

• Age: 65 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Patients, Chinese speaking, in both gender are eligible to be included in the study only if they meet all of the following criteria:
• Meets NIA/AA core clinical criteria for probable AD;
• The body weight is between 45-90kg;
• Aged ≥ 65 and ≤ 85 years old;
• Mild to moderate stage of AD, defined as( MMSE score of 15 through 26) at baseline;
• Has had an MRI scan performed at baseline that has confirmed with a diagnosis of AD, Medial temporal atrophy scale (MTA) is used for routine assessment of the medial temporal lobe, and the MTA score need ≥1.5 (adjusted by age: 65-74 years ≥ 1.5 points, 75-84 years old ≥ 2.0 points);
• Has a PIB-PET scan or CSF result consistent with the presence of amyloid pathology at screening;
• And the patients must have adequate vision and hearing to participate in study assessments; has normal swallowing function, and can complete the medication;
• Have a stable caregiver;
• Can read simple articles and write simple sentences;
• Informed consent, signed informed consent by legal guardian.

You may not qualify if:

• Patients who confirmed with any of the following excluding criteria conditions were not enrolled for the study:
• Early-onset Alzheimer disease (oneset at \<65 years of age) and moderate to severe AD dementia (MMSE 14-0);
• Evidence of other reasons caused cognitive impairment, like vascular dementia, frontotemporal dementia, Parkinson's disease dementia, Lewy body dementia, Huntington's disease, subdural hematoma, communicating hydrocephalus, brain tumor, thyroid disease, vitamin deficiency Or other diseases that may cause cognitive impairment, or serious brain infections (including neurosyphilis, meningitis or encephalitis), etc.;
• There are unstable mental disorders, including major depression (HAMD≥17), severe anxiety disorder (HAMA≥12 points), bipolar disorder, schizophrenia, etc.;
• History of drug or alcohol abuse in the past 5 years;
• Other uncontrolled chronic illnesses, such as severe arrhythmia (ventricular rate \<60 beats/min or \>100 beats/min, or patients with myocardial infarction within 3 months before participating in the trial, or severe heart failure (NY classification III and IV), or severe abnormal blood pressure, systolic blood pressure ≤90mmHg or ≥180mmHg;
• Severe liver or kidney dysfunction (alanine aminotransferase or aspartate transaminase was more than 1.5 times the upper limit of normal, or serum creatinine was more than the upper limit of normal);
• A history of taking cholinesterase inhibitors, memantine, or proprietary Chinese medicines with clear nootropic effects within the past 1 month;
• Has received medications that affect the central nervous system (CNS), except treatments for AD for less than 4 weeks; that is, doses of chronic medications that affect the CNS should be stable for at least 4 weeks;
• One of the following manifestations on cranial MRI:\> 4 cerebral microhemorrhages, evidence of a prior macrohemorrhage, \> 3 lacunar infarcts over 10 mm each, any cortical infarct over 10 mm, or any other clinically significant finding (e.g., any lesion that may account for their cognitive impairment, including but not limited to brain tumor, severe white matter disease with a rating of 3 on the Fazekas scale for WM lesions ,arteriovenous malformation, cavernous hemangioma, or any infarct in a strategic subcortical location);
• History of hypersensitivity to the treatment drugs;
• Participate in other clinical study within the last 30 days;
• Has metal (ferromagnetic) implants, or a cardiac pacemaker and other conditions that could not undergo MRI scan;
• or other conditions that, in the investigator's opinion, could interfere with the analyses of safety and efficacy in this study.

Sponsors & Collaborators

• Dongzhimen Hospital, Beijing: lead

Study Sites (1)

Dongzhimen Hospital ,Beijing University of Chinese Medicine

Beijing, Beijing Municipality, 100700, China

RECRUITING

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Jinzhou Tian, MD,PhD

  Dongzhimen Hospital, Beijing

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jinzhou Tian, MD.PhD

CONTACT

+861084013380; jztian@hotmail.com

Jing Shi, MD

CONTACT

86-10-84011920; shijing87@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice president

Study Record Dates

• First Submitted: February 28, 2021
• First Posted: March 3, 2021
• Study Start: November 9, 2021
• Primary Completion: March 1, 2024
• Study Completion: December 30, 2024
• Last Updated: February 21, 2023

Record last verified: 2023-02

Locations

CN (1)