Clinical trial NCT04041349: Clinical Observation for the Therapeutic Effect of mNGF on Cognitive Decline in Cerebral Small Vessel Disease
Official title: Clinical Observation for the Therapeutic Effect of mNGF on Cognitive Decline in Cerebral Small Vessel Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Cerebral Small Vessel Diseases
Keywords: Cerebral Small Vessel Diseases
Mouse Nerve Growth Factor
cognitive impairment
Lead sponsor: Zhujiang Hospital
Sponsor class: OTHER
Collaborators: name: First Affiliated Hospital, Sun Yat-Sen University
name: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: First Affiliated Hospital of Jinan University
name: Guangdong 999 Brain Hospital
name: Dongguan People's Hospital
name: Houjie Hospital of Dongguan City
name: First Affiliated Hospital of Shantou University Medical College
name: Wuhan University
name: The First Affiliated Hospital of Guangdong Pharmaceutical University
First posted: 2019-08-01
Enrollment: 50
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study was a multicenter, prospective, randomized controlled trial. In this study, 510 patients with cognitive impairment of cerebral small vessel disease who met the inclusion criteria are randomly included in multiple centers and randomized into two groups (standard treatment group and mouse nerve growth factor addition treatment group). The standard treatment group is treated with conventional drugs and cholinesterase inhibitors. In addition to the above treatment, the mouse nerve growth factor addition treatment group is administered with nerve growth factor 20 μg (9000 U)/vial for 14 consecutive days, intramuscularly once a day. Systematic clinical evaluation of patient cognitive function is performed at baseline, 14-day, and 3-month follow-up, and imaging (MR) is also evaluated twice at baseline, 14-day, and 3-month follow-up. At last observe the clinical effect of mouse nerve growth factor on cognitive impairment of cerebral small vessel disease.

Detailed description: Cerebral small vessel disease (CSVD) refers to the disease that involves cerebral small blood vessels, including arterioles, arterioles, capillaries, and venules, etc.The clinical manifestations of CSVD are complex and varied, but cognitive impairment is one of the core clinical manifestations of CSVD, and some patients have gait and sphincter dysfunction.At present, CSVD is an important subtype of vascular cognitive dysfunction and the most common cause of vascular dementia in clinic.Currently, the treatment of cognitive impairment in small cerebral vascular diseases is conducted in two aspects: the treatment and prevention of the structure and function of small cerebral vascular diseases, and the treatment of cognitive dysfunction.The treatments recommended by experts for cognitive dysfunction include cholinesterase inhibitors, nmda-receptor antagonists, and other drugs, but these drugs have not been specifically studied for the treatment of cognitive impairment in small cerebral vascular diseases.The treatment of cognitive impairment in small cerebral vascular disease is still in difficulty, and there is no effective and specific treatment at present.Mouse Nerve Growth Factor (mNGF) is a soluble protein which promotes Nerve Growth, isolated and purified successively by Levi-Montalcini and Cohen in 1959 and 1960.The discovery of NGF makes people realize that some factors are needed to promote the development, growth and maintain the activity of neurons in the process of nervous system, which opens up a new field of neurobiology, for which the two scholars won the 1986 Nobel Prize in physiology.Clinical use of NGF in the treatment of Alzheimer's Disease (AD), NGF injection into Meynert basal ganglia showed that NGF can improve the symptoms of AD and AD induced brain atrophy.Meynert basal ganglia is considered to be the main source of cholinergic neurons and plays an important role in the pathogenesis of AD and Parkinson's Disease (PD). Similar studies in China have also confirmed that nerve growth factor can reduce the symptoms of vascular dementia in stroke patients and delay the development of cognitive dysfunction.It has been found that nerve growth factor, like other special types of macromolecular proteins, can pass through the blood-brain barrier (BBB) through receptor-mediated endocytosis.In the animal studies, BBB integrity was significantly damaged in rats with hypertensive white matter lesions, in which case, nerve growth factor can play a role in protecting neurons, preventing cell apoptosis and promoting nerve reconstruction through BBB.By carrying out this study, the researchers intend to explore the therapeutic effect of rat nerve growth factor on cognitive dysfunction caused by cerebral small vascular disease, and preliminarily explore its imaging mechanism, so as to provide a new direction for further research on drug treatment of cognitive dysfunction caused by cerebral small vascular disease.

Eligibility criteria: Inclusion Criteria:

1. Aged 50-80 years old;
2. Clinical symptoms of acute CSVD, including Transient ischemic attack (TIA) or lacunar infarction, and with related lesions on MRI imaging (acute infarction with diameter \< 20mm on (diffusion weighted imaging) DWI or with diameter of 3-15mm on MRI-T1,T2 or FLAIR);
3. For patients with chronic CSVD symptoms, two or more CSVD imaging markers are required : lacune (number \> = 1), white matter lesion (Fazekas \> = 2), cerebral microbleeds (number \> =1 in deep white matter), enlarged perivascular space(number \> = 10 in basal ganglia);
4. Clinical diagnosis of vascular cognitive impairment or dementia, MMSE score =\<26;
5. Signed informed consent.

Exclusion Criteria:

1. Intracranial or extracranial arterial stenosis of \> 50% luminal stenosis or prior history of endarterectomy of cerebral large arteries;
2. TOAST classification suggested (very) possible cardioembolic stroke;
3. Large cortical or subcortical infarction with diameter \> 1.5cm on MRI; White matter lesions caused by other diseases such as multiple sclerosis; Other central nervous system diseases such as cerebral hemorrhage, brain trauma, epilepsy, encephalitis, hydrocephalus or brain tumors; Oher systemic diseases, such as liver and kidney insufficiency, tumor, etc.;
4. History of alcohol intoxication, drug addiction, or mental disease, or severe aphasia;
5. Contraindication for MRI examination. -

Primary outcomes:
measure: change of Alzheimer's disease assessment scale-cognition (ADAS-cog) score
timeFrame: Baseline -14 days -3 months
Secondary outcomes:
measure: change of Mini-mental State Examination (MMSE)
timeFrame: Baseline -14 days -3 months
measure: Montreal Cognitive Assessment (MoCA) scale
timeFrame: Baseline -14 days -3 months
measure: digit span test
timeFrame: Baseline -14 days -3 months
measure: Activity of Daily Living Scale
timeFrame: Baseline -14 days -3 months
measure: Patient Health Questionnaire-9 Score
timeFrame: Baseline -14 days -3 months
measure: Hamilton anxiety scale
timeFrame: Baseline -14 days -3 months
measure: Hamilton depression scale
timeFrame: Baseline -14 days -3 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Zhujiang Hospiatal
state: Guangdong
Study officials:
affiliation: Zhujiang Hospital
name: Xiaoya Gao, Doctor
role: PRINCIPAL_INVESTIGATOR
References: