Cerebral Small Vessel DiseasesPhase 4NCT04041349
Clinical Observation for the Therapeutic Effect of mNGF on Cognitive Decline in Cerebral Small Vessel Disease
A Phase 4 study testing mouse nerve growth factor in people with Cerebral Small Vessel Diseases, run by Zhujiang Hospital at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 50 to 80 years
- Conditions the study is for
- Cerebral Small Vessel Diseases
- What is being tested?
- mouse nerve growth factor
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteChina
- Study dates
- 7 Sep 2019to 28 Feb 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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. -
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Zhujiang Hospiatal
Guangzhou, Guangdong, 510000
Xiaoya Gao, master, 86-18680282869, gaoxy23@126.com
About this study
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.
Read the 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.
- Conditions
- Cerebral Small Vessel Diseases
- Being tested
- mouse nerve growth factor
- Keywords
- Cerebral Small Vessel Diseases, Mouse Nerve Growth Factor, cognitive impairment
- Medical subject headings
- Cerebral Small Vessel Diseases, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
mouse nerve growth factorDrug
Also called mNGF
mouse nerve growth factor of 20 UG (9000 U)/day for 14 consecutive days by intramuscular injection
| Study group | Role | What they receive |
|---|---|---|
| The standard treatment group | No intervention | The standard treatment group is treated with conventional drugs and cholinesterase inhibitors |
| mouse nerve growth factor (mNGF)group | Experimental | Conventional drugs and cholinesterase inhibitors + mouse nerve growth factor (mNGF) of 20 μg (9000 U)/day for 14 consecutive days by intramuscular injection. Receives: Drug: mouse nerve growth factor |
What is being measured
The primary outcome is the main question the study is designed to answer.
change of Alzheimer's disease assessment scale-cognition (ADAS-cog) score
Cognitive function assessment
Measured: Baseline -14 days -3 months
Secondary outcomes (7)
change of Mini-mental State Examination (MMSE)
Dementia screening scale
Measured: Baseline -14 days -3 months
Montreal Cognitive Assessment (MoCA) scale
A rapid screening tool for mild cognitive impairment
Measured: Baseline -14 days -3 months
digit span test
test the ability to concentrate attention, instantaneous memory and anti - information interference ability
Measured: Baseline -14 days -3 months
Activity of Daily Living Scale
Barthel index was used to reflect the daily life ability of the interviewees
Measured: Baseline -14 days -3 months
Patient Health Questionnaire-9 Score
Depression assessment tool
Measured: Baseline -14 days -3 months
Hamilton anxiety scale
Assess the severity of anxiety symptoms in neurosis and other patients
Measured: Baseline -14 days -3 months
Hamilton depression scale
A commonly used scale in clinical evaluation of depression
Measured: Baseline -14 days -3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2019
- Study start7 Sep 2019
- Primary completion30 Nov 2020 (estimated)
- Study completion28 Feb 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cerebral Small Vessel DiseasesStudies of the same condition, open and under way.
- More trials run by Zhujiang HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Zhujiang Hospital
- Sponsor type
- University, hospital or other
- 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
- Responsible party
- Principal investigator, Gao Xiaoya, Zhujiang Hospital
- Investigators
- Xiaoya Gao, Doctor, Principal investigator, Zhujiang Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04041349
- Sponsor's protocol ID
- 2019-KY-026-02
- Status last verified
- Oct 2020
- First submitted
- 9 Jul 2019
- Last updated
- 2 Nov 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Observation for the Therapeutic Effect of mNGF on Cognitive Decline in Cerebral Small Vessel Disease
- ClinicalTrials.gov ID
- NCT04041349
- Acronym / sponsor ID
- 2019-KY-026-02
- Conditions
- Cerebral Small Vessel Diseases
- Keywords
- Cerebral Small Vessel Diseases, Mouse Nerve Growth Factor, cognitive impairment
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Zhujiang HospitalUniversity, hospital or other
- 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
- Study start
- 7 Sep 2019 (actual)
- Primary completion
- 30 Nov 2020 (estimated)
- Study completion
- 28 Feb 2021 (estimated)
- First posted
- 1 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| The standard treatment group | No intervention | –The standard treatment group is treated with conventional drugs and cholinesterase inhibitors |
| mouse nerve growth factor (mNGF)group | Experimental | Drug: mouse nerve growth factorConventional drugs and cholinesterase inhibitors + mouse nerve growth factor (mNGF) of 20 μg (9000 U)/day for 14 consecutive days by intramuscular injection. |
Who may qualify
- Ages
- 50 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (5 listed)
- 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. -
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| mouse nerve growth factorAlso: mNGFmouse nerve growth factor of 20 UG (9000 U)/day for 14 consecutive days by intramuscular injection | Drug | mouse nerve growth factor (mNGF)group |
Primary outcome
change of Alzheimer's disease assessment scale-cognition (ADAS-cog) score
Time frame: Baseline -14 days -3 months
Cognitive function assessment
7 secondary outcomes
change of Mini-mental State Examination (MMSE)
Time frame: Baseline -14 days -3 months
Montreal Cognitive Assessment (MoCA) scale
Time frame: Baseline -14 days -3 months
digit span test
Time frame: Baseline -14 days -3 months
Activity of Daily Living Scale
Time frame: Baseline -14 days -3 months
Patient Health Questionnaire-9 Score
Time frame: Baseline -14 days -3 months
Hamilton anxiety scale
Time frame: Baseline -14 days -3 months
Hamilton depression scale
Time frame: Baseline -14 days -3 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Xiaoya Gao, Doctor principal investigator
Zhujiang Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing mouse nerve growth factor in people with Cerebral Small Vessel Diseases, run by Zhujiang Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 2 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Xiaoya Gao, Doctor (86-18680282869, gaoxy23@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
change of Alzheimer's disease assessment scale-cognition (ADAS-cog) score (time frame: Baseline -14 days -3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2020.