Clinical trial NCT04301466: Efficacy and Safety of Qi Zhi Tong Luo Capsule in Vascular Cognitive Impairment
Official title: Efficacy and Safety of Qi Zhi Tong Luo Capsule in Vascular Cognitive Impairment: a Randomized, Double-blind, Placebo- Controlled, Multicentre Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Vascular Cognitive Impairment
Qi Zhi Tong Luo Capsule
Randomized Controlled Trial
Lead sponsor: Dongzhimen Hospital, Beijing
Sponsor class: OTHER
Collaborators: name: Shanxi Zhendong Pharmacy Co., Ltd
First posted: 2020-03-10
Enrollment: 362
Sex: ALL
Minimum age (years): 45
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Qi Zhi Tong Luo (QZTL) capsule, a traditional Chinese herbal medicine, which was used to treat stoke-related symptoms, include trouble speaking, paralysis and trouble walking. This study aimed to evaluate the efficacy and safety of QZTL capsule in the treatment of vascular cognitive impairment. This study was designed as randomized, double-blind, parallel, placebo-controlled, multicentre trial. It consisted of a single-blind run-in period using placebo only (2 weeks) and a double-blind treatment phase after randomization (24 weeks), and follow-up 12 weeks after withdrawal.The primary efficacy variables included changes from baseline in the Clinical Dementia Rating scale-Sum Box (CDR-SB) and the Mini-mental State Examination (MMSE) after 24 weeks of treatment. The secondary efficacy measurements include the Clock Drawing Test (CDT), Hopkins Verbal Learning Test (HVLT) and Ability of Daily Living (ADL).


Eligibility criteria: Inclusion Criteria:

1. Decline in cognitive function from a prior baseline and impairment in at least 1 cognitive domain, the domain of cognition including executive function(Trail Making Test-part A(Chinese version,150s)\>98s)), memory function decline (Hopkins verbal learning test free recall(36 points) \<18.5 points), language function decline (Boston naming test (Chinese version 30 items)\<22 points), and visuo-spatial functions (Clock drawing test(10 points)\<8.5 points) ;
2. Evidence of cerebrovascular disease relies on structural magnetic resonance imaging (MRI) , history and clinical feature. The neuroimaging should include at least one of following: a) a single large vessel infarction which was sufficient to cause cognition decline; b) infarction at a single strategic place was sufficient to cause severe cognition decline( the thalamus, angular gyrus, and basal ganglia, including the caudate nucleus and globus pallidus); c) multiple lacunar infarctions (≥3) outside the brainstem, or 2 lacunar infarcts at key locations, a single lacunar focus with extensive white matter lesions(WMLs) ; d) extensive and integrated WMLs(Fazekas scale≥3 points) ; e) intracranial hemorrhage in key parts, or ≥2 intracranial hemorrhages; f) combination of above.
3. There was a clear temporal relationship between a vascular event and onset of cognitive deficit, cognitive impairment should appear within 3 months after a stroke, or abrupt deterioration, or stepwise progression of deficits; or cognitive impairment may be related to vascular factors, the Hachinski Ischemia scale (HIS) score ≥7;
4. And the patients must have adequate vision and hearing to participate in study assessments;
5. Have a stable caregiver;
6. Can read simple articles and write simple sentences;
7. Informed consent, signed informed consent by legal guardian.

Exclusion Criteria:

1. Evidence of other reasons caused cognitive impairment, like Alzheimer disease, frontotemporal dementia, Parkinson disease dementia, dementia with Lewy bodies, Huntington disease, etc;
2. Subdural hematoma, traffic hydrocephalus, brain tumor, thyroid disease, vitamin deficiency, or other diseases which can lead to cognitive impairment;
3. Major depression (Hamilton depression rating scale \[HAMD\] ≥17) or other mental disorders ;
4. History of drug or alcohol abuse in the past 6 month;
5. History of epilepsy;
6. Patients with myasthenia gravis;
7. Subject cannot complete related test due to severe neurologic deficits;
8. Other uncontrolled chronic illnesses, like severe cardiovascular disease (severe arrhythmia, myocardial infarction within 3 months, severe heart failure(New York Heart Association Functional Classification III and IV,); uncontrolled hypertension, diabetes);
9. 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);
10. Concomitant use of the anticonvulsants, antipsychotics, cholinomimetic drugs, anticholinergic agents, anti-Parkinson drugs, cholinesterase inhibitors, memantine, nootropic drug, nimodipine, anticholinergic or anticholinergic antidepressant or anxiolytic and other cognition enhancers within 1 month;
11. Severe asthma and chronic obstructive pulmonary disease;
12. Patients with severe indigestion, gastrointestinal obstruction, gastric or duodenal ulcers;
13. Patients with glaucoma;
14. History of hypersensitivity to the treatment drugs;
15. Participate in other clinical study.

Primary outcomes:
measure: Changes of Clinical Dementia Rating-Sum of the Boxes scale (CDR-SB) from baseline
timeFrame: week 0, 12, 24,36
measure: Changes of Mini-mental State Examination(MMSE from baseline
timeFrame: week 0, 12, 24,36
Secondary outcomes:
measure: Changes of Hopkins Verbal Learning Test from baseline
timeFrame: week 0, 12, 24,36
measure: Changes of Clock drawing test from baseline
timeFrame: week 0, 12, 24,36
measure: Changes of Ability of daily living scale from baseline
timeFrame: week 0, 12, 24,36
Other outcomes:
Locations:
city: Beijing
country: China
facility: Dongzhimen Hospital ,Beijing University of Chinese Medicine
state: Beijing
Study officials:
References: