Ignite Creation Date:
2024-05-06 @ 8:28 PM
Last Modification Date:
2024-10-26 @ 3:28 PM
Study NCT ID:
NCT06391645
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-04-30
First Post:
2024-03-08
Brief Title:
Nerve Growth Factor Encapsulated With 2-methacryloyloxyethyl Phosphorylcholine Nanocapsules in the Treatment of Amyotrophic Lateral Sclerosis
Sponsor:
Beijing Tiantan Hospital
Organization:
Beijing Tiantan Hospital
Study Overview
Official Title:
Nerve Growth Factor Encapsulated With 2-methacryloyloxyethyl Phosphorylcholine Nanocapsules in the Treatment of Amyotrophic Lateral Sclerosis
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
NATURAL
Brief Summary:
Amyotrophic lateral sclerosis ALS is one of the most lethal neurodegenerative diseases with most patients dying from respiratory failure 3-5 years after the onset The purpose of this study is to explore the efficacy and safety of nerve growth factor NGF encapsulated with 2-methacryloyloxyethyl phosphorylcholine MPC nanocapsules in the treatment of ALS patients
Detailed Description:
Amyotrophic lateral sclerosis ALS is one of the most lethal neurodegenerative diseases Most patients die due to respiratory failure 3-5 years after disease onset Due to the low permeability and blocking of the blood-brain barrier BBB on more than 95 of all kinds of drugs the drug treatment of ALS is relatively limited Although a series of studies have been carried out on new therapies to ALS such as monoclonal antibodies represented by ozanezumab and antisense oligonucleotides represented by tofersen the conclusions are mostly limited to safety evaluation
Nerve growth factor NGF provides protection andor regeneration for neurons in the peripheral and central nervous system CNS which is considered to be a nerve regeneration agent with great therapeutic potential The phase I clinical trial of intravenous recombinant human nerve growth factor rhNGF showed that on the premise of ensuring safety only a trace of NGF 36-738 ngml within 5 minutes was detected in the plasma samples of the subjects who were injected with rhNGF 10 μgkg the maximum dose of this trial design
In purpose of improving the therapeutic effect of NGF the investigators plan to encapsulate NGF in nanoparticles linked by 2-methacryloyloxyethyl phosphorylcholine MPC consisting of one molecule of choline and one molecule of acetylcholine analog After intravenous administration the drug particles are effectively delivered to the CNS via receptor-mediated transcytosis RMT with the help of acetylcholine transporter and choline transporter widely expressed on brain capillary endothelial cells The animal experiments have confirmed that intravenous injection of MPC encapsulated NGF capsule nNGF can effectively prolong the survival time of SOD1G93A mice reduce the body weight loss and delay the time of dyskinesia onset compared with NGF Similar results were obtained in the rhesus monkey model
The purpose of this study is to explore the efficacy and safety of NGF encapsulated with MPC nanocapsules in the treatment of ALS patients
This is a prospective randomized open-label blinded endpoint PROBE clinical trial The trial planned to enroll 60 ALS patients aged 18-80 years with disease duration 6 months to 3 years with forced vital capacity FVC 85 of predicted value
Patients will be randomly assigned to one of the following 3 groups at 11 ratio
Treatment group 1 NGF 60ml wrapped in MPC nanomaterials dose was given as 320 μgml was injected intravenously every week for 12 weeks including one administration at the starting point for a total of 13 times as well as maintaining original basic drugs and rehabilitation treatment
Treatment group 2 NGF 37ml wrapped in MPC nanomaterials dose was given as 320 μgml was injected intravenously every week for 12 weeks including one administration at the starting point for a total of 13 times as well as maintaining original basic drugs and rehabilitation treatment
Control group NGF 60ml dose was given as 320 μgml was injected intravenously every week for 12 weeks including one administration at the starting point for a total of 13 times as well as maintaining original basic drugs and rehabilitation treatment
Face to face interviews will be made on baseline 284 days after randomization 847 days after randomization and 1207 days after randomization Online interviews will be made on 18014 days and 1 year 14 days after randomization
The primary outcome Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised ALSFRS-R scores of ALS patients in the treatment group and the control group after 3 months of NGF injection will be compared by Wilcoxon rank sum test and β and 95 confidence interval CI will be calculated The survival mortality of ALS patients in treatment group and control group will be analyzed by COX regression model and hazard ratio HR value and 95CI were be calculated Survival curve will be calculated by Nelson-Aalen cumulative risk curve and Grays test will be used for comparison between groups
Nerve growth factor NGF provides protection andor regeneration for neurons in the peripheral and central nervous system CNS which is considered to be a nerve regeneration agent with great therapeutic potential The phase I clinical trial of intravenous recombinant human nerve growth factor rhNGF showed that on the premise of ensuring safety only a trace of NGF 36-738 ngml within 5 minutes was detected in the plasma samples of the subjects who were injected with rhNGF 10 μgkg the maximum dose of this trial design
In purpose of improving the therapeutic effect of NGF the investigators plan to encapsulate NGF in nanoparticles linked by 2-methacryloyloxyethyl phosphorylcholine MPC consisting of one molecule of choline and one molecule of acetylcholine analog After intravenous administration the drug particles are effectively delivered to the CNS via receptor-mediated transcytosis RMT with the help of acetylcholine transporter and choline transporter widely expressed on brain capillary endothelial cells The animal experiments have confirmed that intravenous injection of MPC encapsulated NGF capsule nNGF can effectively prolong the survival time of SOD1G93A mice reduce the body weight loss and delay the time of dyskinesia onset compared with NGF Similar results were obtained in the rhesus monkey model
The purpose of this study is to explore the efficacy and safety of NGF encapsulated with MPC nanocapsules in the treatment of ALS patients
This is a prospective randomized open-label blinded endpoint PROBE clinical trial The trial planned to enroll 60 ALS patients aged 18-80 years with disease duration 6 months to 3 years with forced vital capacity FVC 85 of predicted value
Patients will be randomly assigned to one of the following 3 groups at 11 ratio
Treatment group 1 NGF 60ml wrapped in MPC nanomaterials dose was given as 320 μgml was injected intravenously every week for 12 weeks including one administration at the starting point for a total of 13 times as well as maintaining original basic drugs and rehabilitation treatment
Treatment group 2 NGF 37ml wrapped in MPC nanomaterials dose was given as 320 μgml was injected intravenously every week for 12 weeks including one administration at the starting point for a total of 13 times as well as maintaining original basic drugs and rehabilitation treatment
Control group NGF 60ml dose was given as 320 μgml was injected intravenously every week for 12 weeks including one administration at the starting point for a total of 13 times as well as maintaining original basic drugs and rehabilitation treatment
Face to face interviews will be made on baseline 284 days after randomization 847 days after randomization and 1207 days after randomization Online interviews will be made on 18014 days and 1 year 14 days after randomization
The primary outcome Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised ALSFRS-R scores of ALS patients in the treatment group and the control group after 3 months of NGF injection will be compared by Wilcoxon rank sum test and β and 95 confidence interval CI will be calculated The survival mortality of ALS patients in treatment group and control group will be analyzed by COX regression model and hazard ratio HR value and 95CI were be calculated Survival curve will be calculated by Nelson-Aalen cumulative risk curve and Grays test will be used for comparison between groups
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None