A Retrospective Study to Investigate the Additive Effectiveness of Chinese Herbal Medicine in Alzheimer's Disease

In China, herbal therapy as a complementary therapy is very popular. Should conventional therapy (such as donepezil and memantine) combined with herbal therapy make add-on benefit? Cognition, activities of daily living and behavioral symptoms will be assessed. Data will be collected from the medical records of patients with Alzheimer's disease (AD) in memory clinics.

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease
• Intervention / Treatment: Dietary supplement: GRAPE granules

Detailed Description

Conventional therapy (CT), such as donepezil and memantine are well- known short-term treatments for the symptoms of Alzheimer's disease (AD). The efficacy of them, however, drops below baseline level after 9 months. Should Chinese herbal medicine make add-on benefit? The GRAPE formula was designed by Prof. J Tian, a prepared granules of Chinese herbs, according to Qifuyin in Jing Yue Quan Shu (published in A.D. 1624). Patients treated with CT+herbal therapy or CT alone for up to and over 12 months are collected. Cognition, activities of daily living and behavioral symptoms are selected as outcomes for assessing the effectiveness.

• Study Type: Observational
• Enrollment (Actual): 120

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Dongzhimen Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 46 years to 81 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

AD patients involved in this retrospective, observational study will be selected from the clinic registration system of memory clinics in Beijing. All the participants underwent routine clinical assessments, including detailed medical history, cognitive and neuropsychological tests, neurological examinations, laboratory tests (i.e. thyroid function, folic acid levels, vitamin B12 levels, and routine blood tests), and neuroimaging. Participants with detailed medical history will be sampled and grouped into two cohorts according the therapies received.

Description

Inclusion Criteria:

• Gradual and progressive change in cognitive functions for a period greater than 6 months;
• Objective evidence of significantly impaired episodic memory together with at least one of other cognitive domains on testing;
• Global cognitive decline measured by mini-mental state examination (MMSE) adjusted for education: ≤22 for illiteracy, ≤23 for primary school, ≤24 for middle school,≤26 for high education;
• Impaired abilities of daily living, ADLs score ≥16;
• Clinical Dementia Rating (CDR) total score 0.5~3.0;
• ≤4 point on Hachinski Ischaemic Score (HIS);
• Age-adjusted medial temporal lobe atrophy scale (MTA-scale) based on coronary magnetic resonance imaging (MRI) scan of the brain (1.0 or more for ≤65 years; 1.5 or more for ≤75 years and 2.0 or more for ≥75 years);
• Other causes of dementia excluded.

Exclusion Criteria:

• Sudden onset of cognitive disorder with focal nervous system signs in the early stages of disease, (e.g., incomplete paralysis, anesthesia, dysfunctional visual field, and dystaxia);
• Early occurrence of the following symptoms: gait disturbances, seizures, extrapyramidal signs, hallucinations and cognitive fluctuations;
• Any major psychiatric disorders (e.g., DSM-IV(Diagnostic and Statistical Manual of Mental Disorders) defined psychosis, major depression, bipolar disorder, or alcohol or substance abuse);
• Other conditions that may explain cognitive impairment (e.g., hypothyroidism, electrolyte imbalance, toxic, inflammatory, and metabolic disorders).

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Conventional therapy with herbs; Patients were treated with conventional therapy with Chinese herbal medicine (GRAPE granules).	Dietary supplement: GRAPE granules; GRAPE granules was mainly consisted of herbal medicines: Ren Shen (Ginseng, 10g/d), Di Huang (Rehmannia glutinosa, 30g/d), Shi Cangpu (Acorus tatarinowii, 10g/d), Yuan Zhi (Polygala tenuifolia, 10g/d), Yin Yanghuo (Epimedium brevicornu, 10g/d), Shan Zhuyu (Cornus officinalis, 10g/d), Rou Congrong (Cistanche deserticola, 10g/d), Yu Jin (Curcuma aromatica, 10g/d), Dan Shen (Salvia miltiorrhiza, 10g/d), Tian Ma (Angelica sinensis, 10g/d), Tian ma (Gastrodia elata, 10g/d), and Huang Lian (Berberine, 10g/d), which were supplied by Beijing Tcmages Pharmaceutical Co., LTD, Each bag of granules with 150ml warm water melt was taken orally twice a day.
Conventional therapy alone; In conventional therapy group, donepezil was the commonly used ChEI(cholinesterase inhibitor) to treat mild to severe AD patients. Memantine, a NMDA(N-methyl-D-aspartate ) antagonist, was given to moderate and severe AD patients. The dose of donepezil ranged from 5 to 10 mg once a day according to patients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mini-Mental State Examination (MMSE)	Change of global cognition was measured by MMSE, a 30-point scale, higher score indicates better cognition.	Up to 12 months, repeated measurement every 3 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Activities of Daily Living (ADLs)	Both basic ADLs (6-items) and instrumental ADLs (8-items) were measured. The ADLs contain 14 items (score 1-4), the range is 14 to 56, and higher scores indicate worse function.	Up to 12 months, repeated measurement every 3 months.
Clinical Dementia Rating (CDR)	The CDR is a 5-point scale used to characterize six domains of cognitive and functional performance applicable to Alzheimer disease and related dementias. 0 = Normal, 0.5 = Very Mild Dementia, 1 = Mild Dementia, 2 = Moderate Dementia, 3 = Severe Dementia.	Up to 12 months, repeated measurement every 3 months.
Neuropsychiatric Inventory (NPI)	NPI was used for rating the behavioral and psychological symptoms of dementia (BPSD), including 12-items, with a score rang from 0-144, higher score indicates worse state.	Up to 12 months, repeated measurement every 3 months.

Collaborators and Investigators

• Sponsor: Dongzhimen Hospital, Beijing
• Collaborators: Chinese PLA General Hospital; Peking University Third Hospital; Beijing Hospital
• Investigators: Principal Investigator: Jinzhou TIAN, Dr, Dongzhimen Hospital, BUCM

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2017
• Primary Completion (Actual): July 31, 2021
• Study Completion (Actual): July 31, 2021

Study Registration Dates

• First Submitted: July 17, 2017
• First Submitted That Met QC Criteria: July 17, 2017
• First Posted (Actual): July 19, 2017

Study Record Updates

• Last Update Posted (Actual): August 20, 2021
• Last Update Submitted That Met QC Criteria: August 18, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Complementary therapies
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: 2017-IRT-0810

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: The datasets are available from the PI on reasonable request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No