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Clinical Observation for the Therapeutic Effect of mNGF on Cognitive Decline in Cerebral Small Vessel Disease

Primary Purpose

Cerebral Small Vessel Diseases

Status
Unknown status
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
mouse nerve growth factor
Sponsored by
Zhujiang Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cerebral Small Vessel Diseases focused on measuring Cerebral Small Vessel Diseases, Mouse Nerve Growth Factor, cognitive impairment

Eligibility Criteria

50 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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. -

Sites / Locations

  • Zhujiang HospiatalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

The standard treatment group

mouse nerve growth factor (mNGF)group

Arm Description

The standard treatment group is treated with conventional drugs and cholinesterase inhibitors

Conventional drugs and cholinesterase inhibitors + mouse nerve growth factor (mNGF) of 20 μg (9000 U)/day for 14 consecutive days by intramuscular injection.

Outcomes

Primary Outcome Measures

change of Alzheimer's disease assessment scale-cognition (ADAS-cog) score
Cognitive function assessment

Secondary Outcome Measures

change of Mini-mental State Examination (MMSE)
Dementia screening scale
Montreal Cognitive Assessment (MoCA) scale
A rapid screening tool for mild cognitive impairment
digit span test
test the ability to concentrate attention, instantaneous memory and anti - information interference ability
Activity of Daily Living Scale
Barthel index was used to reflect the daily life ability of the interviewees
Patient Health Questionnaire-9 Score
Depression assessment tool
Hamilton anxiety scale
Assess the severity of anxiety symptoms in neurosis and other patients
Hamilton depression scale
A commonly used scale in clinical evaluation of depression

Full Information

First Posted
July 9, 2019
Last Updated
October 30, 2020
Sponsor
Zhujiang Hospital
Collaborators
First Affiliated Hospital, Sun Yat-Sen University, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, First Affiliated Hospital of Jinan University, Guangdong 999 Brain Hospital, Dongguan People's Hospital, Houjie Hospital of Dongguan City, First Affiliated Hospital of Shantou University Medical College, Wuhan University, The First Affiliated Hospital of Guangdong Pharmaceutical University
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1. Study Identification

Unique Protocol Identification Number
NCT04041349
Brief Title
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

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Unknown status
Study Start Date
September 7, 2019 (Actual)
Primary Completion Date
November 30, 2020 (Anticipated)
Study Completion Date
February 28, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Zhujiang Hospital
Collaborators
First Affiliated Hospital, Sun Yat-Sen University, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, First Affiliated Hospital of Jinan University, Guangdong 999 Brain Hospital, Dongguan People's Hospital, Houjie Hospital of Dongguan City, First Affiliated Hospital of Shantou University Medical College, Wuhan University, The First Affiliated Hospital of Guangdong Pharmaceutical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cerebral Small Vessel Diseases
Keywords
Cerebral Small Vessel Diseases, Mouse Nerve Growth Factor, cognitive impairment

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
The standard treatment group
Arm Type
No Intervention
Arm Description
The standard treatment group is treated with conventional drugs and cholinesterase inhibitors
Arm Title
mouse nerve growth factor (mNGF)group
Arm Type
Experimental
Arm Description
Conventional drugs and cholinesterase inhibitors + mouse nerve growth factor (mNGF) of 20 μg (9000 U)/day for 14 consecutive days by intramuscular injection.
Intervention Type
Drug
Intervention Name(s)
mouse nerve growth factor
Other Intervention Name(s)
mNGF
Intervention Description
mouse nerve growth factor of 20 UG (9000 U)/day for 14 consecutive days by intramuscular injection
Primary Outcome Measure Information:
Title
change of Alzheimer's disease assessment scale-cognition (ADAS-cog) score
Description
Cognitive function assessment
Time Frame
Baseline -14 days -3 months
Secondary Outcome Measure Information:
Title
change of Mini-mental State Examination (MMSE)
Description
Dementia screening scale
Time Frame
Baseline -14 days -3 months
Title
Montreal Cognitive Assessment (MoCA) scale
Description
A rapid screening tool for mild cognitive impairment
Time Frame
Baseline -14 days -3 months
Title
digit span test
Description
test the ability to concentrate attention, instantaneous memory and anti - information interference ability
Time Frame
Baseline -14 days -3 months
Title
Activity of Daily Living Scale
Description
Barthel index was used to reflect the daily life ability of the interviewees
Time Frame
Baseline -14 days -3 months
Title
Patient Health Questionnaire-9 Score
Description
Depression assessment tool
Time Frame
Baseline -14 days -3 months
Title
Hamilton anxiety scale
Description
Assess the severity of anxiety symptoms in neurosis and other patients
Time Frame
Baseline -14 days -3 months
Title
Hamilton depression scale
Description
A commonly used scale in clinical evaluation of depression
Time Frame
Baseline -14 days -3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Aged 50-80 years old; 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); 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); Clinical diagnosis of vascular cognitive impairment or dementia, MMSE score =<26; Signed informed consent. Exclusion Criteria: Intracranial or extracranial arterial stenosis of > 50% luminal stenosis or prior history of endarterectomy of cerebral large arteries; TOAST classification suggested (very) possible cardioembolic stroke; 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.; History of alcohol intoxication, drug addiction, or mental disease, or severe aphasia; Contraindication for MRI examination. -
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xiaoya Gao, Doctor
Phone
86-18680282869
Email
gaoxy23@126.com
First Name & Middle Initial & Last Name or Official Title & Degree
Xiaomei Liang
Phone
86-13602497928
Email
nfylxm@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xiaoya Gao, Doctor
Organizational Affiliation
Zhujiang Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Zhujiang Hospiatal
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiaoya Gao, master
Phone
86-18680282869
Email
gaoxy23@126.com

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Clinical Observation for the Therapeutic Effect of mNGF on Cognitive Decline in Cerebral Small Vessel Disease

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