Guilingji Capsule for Mild-to-moderate Cognitive Impairment

Efficacy and Safety of Guilingji Capsule in Older Adults With Mild-to-Moderate Cognitive Impairment (Kidney and Marrow Deficiency Pattern)

This study is aiming to evaluate the efficacy and safety of Guilingji capsule in older adults with mild-to-moderate cognitive impairment who diagnosed as the kidney and marrow deficiency pattern in TCM. A total of 348 participants are evenly assigned to two arms. In the intervention arm, participants receive Guilingji capsule and Ginko Biloba Extract mimetic in combination, while the other arm will receive Ginko Biloba Extract tablet with Gulingji mimetic.

Study Overview

• Status: Unknown
• Conditions: Cognitive Dysfunction
• Intervention / Treatment: Drug: Gulingji capsules; Drug: Ginko Biloba Extract tablet

Detailed Description

This study is a multi-center, randomized, positive control, noninferiority clinical trials. Experimental arm (174 cases) take 0.6 g of Gulingji capsules once a day and 19.2 mg of Ginko Biloba Extract mimetic three times a day. Active Comparator arm (174 cases) should take 0.6 g of Gulingji mimetic once a day and 19.2 mg of Ginko Biloba Extract tablet three times a day. The intervention lasted for 24 weeks. Clinical researchers, participants and statisticians are blinded to the treatment assignment throughout the study. Co-primary efficacy endpoints are change from baseline to week 12 and 24 in Mini-Mental State Examination score and Montreal Cognitive Assessment (MoCA) total score.Change from baseline to week 12 and 24 in Clinical Dementia Rating score, Alzheimer's Disease Assessment Scale-Cognitive subscale score, Activities of Daily Living, and Chinese Medicine Symptom Scale scoreare additional endpoints. Prespecified secondary biomarker endpoint is change from baseline in the serum level of acetylcholine and acetylcholinesterase at week 24.

• Study Type: Interventional
• Enrollment (Anticipated): 348
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100091
      • Li Hao

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 58 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Aged between 60 and 85 years old
2. With a disease course ≥ 6 months and confirmed by others
3. Mini-Mental State Examination (MMSE) score between 10 and 26, or MMSE score >26 but Montreal Cognitive Assessment (MoCA) score<26
4. Meeting the diagnostic criteria of mild-to-moderate cognitive impairment
5. Meeting the diagnostic criteria of kidney deficiency pattern in Traditional Chinese medicine
6. Screening visit brain MRI and CT scan consistent with the diagnosis of mild-to-moderate cognitive impairment
7. Adequate visual and auditory abilities to perform all aspects of the cognitive and functional assessments
8. Received a primary and/or a higher education
9. Lives at home with appropriate caregiver capable of accompanying the subject on all clinic visits, or community dwelling with caregiver capable of accompanying the subject on all clinic visits and visiting with the subject approximately 5 times per week for the duration of the study
10. Signed and dated written informed consent. The subject's caregiver must also consent to participate in the study

Exclusion Criteria:

1. Significant neurological disease, other than AD MCI and VaD, that may affect cognition, such as the Parkinson's disease, the Huntington's disease, normal pressure hydrocephalus, brain tumors, progressive supra-nuclear palsy, epilepsy, chronic subdural hematoma and multiple sclerosis, history of severe head trauma with persistent neurological deficits or known abnormal brain structure
2. Thyroid disease, vitamin B12 or folic acid deficiency, severe anemia or malnutrition, serious heart, liver, lung, kidney and other organ diseases that may affect the cognitive function
3. Allergic to Ginkgo products
4. Use of any other medications with the potential to affect cognition
5. Current presence of a clinically important major psychiatric disorder or symptom
6. Alcohol addiction, or long-term use of antipsychotic drugs, or a history of severe head trauma
7. Cannot complete with cognitive function examines.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; In this arm, patients take 0.6g of Gulingji capsules, 2 hours before breakfast, served with light salt water once a day. Also an oral take of 19.2mg Ginko Biloba Extract mimetic three times a day. Treatment lasts for 24 weeks.	Drug: Gulingji capsules; Patients take 0.6g of Gulingji capsules, 2 hours before breakfast, served with light salt water once a day. Also an oral take of 19.2mg Ginko Biloba Extract mimetic three times a day. Treatment lasts for 24 weeks.
Active Comparator: Control; In this arm, patients take 0.6g of Gulingji mimetic, 2 hours before breakfast, served with light salt water once a day. Also an oral take of 19.2mg Ginko Biloba Extract tablet three times a day. Treatment lasts for 24 weeks.	Drug: Ginko Biloba Extract tablet; Patients take 0.6g of Gulingji mimetic, 2 hours before breakfast, served with light salt water once a day. Also an oral take of 19.2mg Ginko Biloba Extract tablet three times a day. Treatment lasts for 24 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Change From Baseline in Mini-Mental State Examination (MMSE) Total Score at Week 12 and 24	MMSE is a 30-point questionnaire and contains items assessing orientation, memory, attention and calculation, naming and visuospatial skills of patients.	Baseline,12th week±3 days, 24th week±3 days
The Change From Baseline in Montreal Cognitive Assessment (MoCA) Total Score at Week 12 and 24	MoCA is a 30-point questionnaire and evaluates orientation, executive function, language ability, short-term memory, attention and visuospatial ability.	Baseline,12th week±3 days, 24th week±3 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Change From Baseline in Clinical Dementia Rating (CDR) Total Score at Week 12 and 24	The CDR test is a numeric scale used to quantify the severity of symptoms of dementia. It sums 6 clinical ratings: 1) memory, 2) orientation, 3) judgment and problem solving, 4) involvement in community affairs, 5) home and hobbies, and 6) personal care based on the CDR interview. The CDR includes discussions with the participant and caregiver using a structured format. CDR total score range is 0 (least impairment) to 18 (most impairment); a negative change from baseline indicates an improvement.	Baseline,12th week±3 days, 24th week±3 days
The Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Total Score at Week 12 and 24	The ADAS-Cog is a multi-item, objective measure of cognitive function. Analysis of the ADAS-Cog for this study is based upon an 12 item score from the following items 1) word recall task, 2) naming objects and fingers, 3) following commands, 4) constructional praxis, 5) ideational praxis, 6) orientation, 7) word recognition, 8) remembering test instructions, 9) spoken language ability, 10) word finding difficulty in spontaneous speech, 11) comprehension, and 12) attention during the test. The ADAS-Cog ranged from 0 to 75 points, with higher scores indicating a greater degree of impairment. A negative change from baseline indicates a decrease in cognitive impairment.	Baseline,12th week±3 days, 24th week±3 days
The Change From Baseline in Activities of Daily Living (ADL) Total Score at Week 12 and 24	The ADL is a test used in healthcare to evaluate the people's daily self care activities.	Baseline,12th week±3 days, 24th week±3 days
The Change From Baseline in The Chinese Medicine Symptom Scale (CM-SS) Total Score at Week 12 and 24	The CM-SS is a tool, designed according to the Guiding Principles of Clinical Research on New Drugs of Traditional Chinese Medicine issued in 2002, to evaluate the effects of treatments on Traditional Chinese medicine patterns (here refers to kidney deficiency pattern). Scoring is mainly based on some typical TCM symptoms, such as tongue coating and pulse.	Baseline,12th week±3 days, 24th week±3 days
The Change From Baseline in The Serum Level of Acetylcholine and Acetylcholinesterase at Week 24	Acetylcholine and acetylcholinesterase are potential circulatory biomarkers of cognitive dysfunction.	Baseline, 24th week±3 days

Collaborators and Investigators

• Sponsor: Xiyuan Hospital of China Academy of Chinese Medical Sciences
• Collaborators: Peking University First Hospital; Guang'anmen Hospital of China Academy of Chinese Medical Sciences; Beijing Hospital; Beijing Shijitan Hospital, Capital Medical University; The First Affiliated Hospital of Henan University of Traditional Chinese Medicine; Shanxi Dayi Hospital; Shaanxi Hospital of Traditional Chinese Medicine; Shandong University of Traditional Chinese Medicine; Huadong Hospital; Longhua Hospital; Beijing Xuanwu Traditional Chinese Medicine Hospital
• Investigators: Study Chair: Hao Li, Institute of Geriatrics, Xiyuan Hospital, China Academy of Chinese Medical Sciences,

Publications and helpful links

General Publications

• Liu NY, Pei H, Liu MX, Liu LT, Fu CG, Li H, Chen KJ. Efficacy and Safety of Guilingji Capsules () for Treating Mild-to-Moderate Cognitive Impairment: Study Protocol for A Randomized, Double-Blind, Positive-Controlled, Multicenter and Noninferiority Trial. Chin J Integr Med. 2020 Aug;26(8):577-582. doi: 10.1007/s11655-020-2723-5. Epub 2020 Aug 5.

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2018
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: August 23, 2018
• First Submitted That Met QC Criteria: August 23, 2018
• First Posted (Actual): August 27, 2018

Study Record Updates

• Last Update Posted (Actual): August 27, 2018
• Last Update Submitted That Met QC Criteria: August 23, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Randomized clinical trial; Traditional Chinese medicine; Mild-to-moderate cognitive impairment
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: 2018XLA039-2

Drug and device information, study documents

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