A study of plasminogen in patients with amyotrophic lateral sclerosis and Parkinson’s disease
| ISRCTN | ISRCTN13974483 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN13974483 |
| Secondary identifying numbers | CA-18-08 |
- Submission date
- 22/01/2023
- Registration date
- 27/01/2023
- Last edited
- 14/11/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nervous System Diseases
Plain English Summary
Background and study aims
The plasminogen activator (PA) system, a general system that breaks proteins down into smaller peptides (proteolysis), has been suggested to be involved in neurodegeneration and regeneration processes in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), a lethal motoneuron disease. During the development of neurodegenerative disorders, including, CNS pathological proteins (including conformationally abnormal proteins or CAPs), i.e., misfolded proteins, denatured proteins and protein aggregates, accumulate inside and between neurons. CNS pathological protein aggregates are toxic to neurons and have an ‘infectivity’ property, allowing them to spread and propagate between neurons, which causes the death of neurons and the rapid expression of tissue plasminogen activator (tPA) in local neurons and microglia. Upon administration, plasminogen rapidly passes through the blood-brain-barrier, possibly through tight junctions and transport by endothelial cells, and arrives in the injured extracellular area, where it colocalizes with tPA on CAP aggregates, and therefore efficiently generates plasmin in individuals with ALS. The formed plasmin rapidly degrades intercellular CNS pathological protein aggregates, and the remaining soluble fragments, i.e., plasmin-generated protein fragments are taken up by microglial cells through endocytosis and subsequently degraded by lysosomes in these cells. In addition, plasminogen/plasmin may directly degrade intracellular CNS pathological protein aggregates or indirectly interact with other components to further enhance intracellular degradation. Plasminogen/plasmin also enters the nucleus to directly or indirectly regulate gene transcription and protein translation, which may further contribute to a decrease in neurodegeneration and an increase in neuroregeneration. Importantly, through the mechanisms proposed above, increases in intracellular and extracellular plasminogen/plasmin levels effectively clear CNS pathological proteins both inside and outside neurons and inhibit the spread of propagative CNS pathological proteins between neurons, and further in combination with its other neuroprotective effects, alleviates neurodegeneration, promotes neuroregeneration and may even restore normal neural functions. Thus, this study will investigate whether plasminogen is an effective therapeutic strategy to inhibit ALS disease progression, reverse disease symptoms, or even treat the disease.
Who can participate?
Patients diagnosed with ALS or PD
What does the study involve?
This study involves the treatment of plasminogen in ALS or PD
What are the possible benefits and risks of participating?
Patients can get free medication, and the clinical symptoms of ALS such as disability will be improved after the administration of the drug. Considering the properties of plasminogen, there may be the risk of bleeding, hypersensitivity reactions and infection after receiving plasminogen.
The study involves the effects of plasminogen on ALS patients.
Where is the study run from?
The intervention was performed at the home of patients or Beijing Chang’an Chinese and Western Integrated Medicine Hospital
When is the study starting and how long is it expected to run for?
January 2018 to October 2021
Who is funding the study?
Talengen Institute of Life Sciences (China)
Who is the main contact?
1. Dr Jinan Li (Principal investigator), jnl@talengen-pharma.com
2. Ms Chunying Guo (public/scientific contact), guocy@talengen-pharma.com
Contact information
Public
Room C602G
289 Digital Peninsula
Shunfeng Industrial Park
No.2 Red Willow Road
Futian District
Shenzhen
518000
China
| Phone | +86 15919440001 |
|---|---|
| guocy@talengen-pharma.com |
Principal Investigator
Room C602G
289 Digital Peninsula
Shunfeng Industrial Park
No.2 Red Willow Road
Futian District
Shenzhen
518000
China
| Phone | +86 13810850852 |
|---|---|
| jnl@talengen-pharma.com |
Scientific
Beijing Chang’an Chinese and Western Integrated Medicine Hospital
Beijing
100010
China
| Phone | +86-13811582746 |
|---|---|
| htzdm2011@163.com |
Study information
| Study design | One-arm open-label non-randomized interventional study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Home, Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | A study of plasminogen in patients with amyotrophic lateral sclerosis and Parkinson’s disease |
| Study hypothesis | The use of plasminogen effectively clears CNS pathological proteins, exerts neuroprotective effects, alleviates neurodegeneration, promotes neuroregeneration and may even restore normal neural functions in patients with amyotrophic lateral sclerosis and Parkinson’s disease. |
| Ethics approval(s) | Approved 05/09/2018, The Ethics Committee of Beijing Chang’an Chinese and Western Integrated Medicine Hospital (19 Zaolinqian St, Xicheng District, Beijing, China; +86-13522667371; 421337949@qq.com), ref: none provided |
| Condition | Amyotrophic lateral sclerosis and Parkinson’s disease |
| Intervention | Plasminogen is a protein being studied as a potential treatment for amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD). Currently, there are only a few FDA-approved drugs to treat ALS or PD, but they do not have a significant impact on survival or disease progression. Therefore, researchers are looking for new and effective ways to treat ALS and PD. The study was conducted by clinical doctors or nursing staff with more than 5 years of clinical work experience. They administered the treatment face-to-face, either at the patient's home or at the Beijing Chang’an Chinese and Western Integrated Medicine Hospital. The study was an open-label, one-arm, and non-randomized study. The treatment duration was 72 weeks. The treatment was given through intravenous injection, at a dose of 50-200 mg each time, 1 time per 1-3 days, two weeks as one treatment course, and 2 weeks intervals between courses. Sometimes, the intravenous injection was combined with atomization inhalation, which was administered once a day, 10 mg each time, beginning on the third day of treatment. The patients' clinical symptoms of ALS were measured using the Revised Amyotrophic Lateral Sclerosis Functional Rating (ALSFRS-R) or by trained clinical evaluators. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Plasminogen |
| Primary outcome measure | Current primary outcome measure as of 09/11/2023: Motor function measured using the ALS Functional Rating Scale-Revised (ALS-FRS-R) scale at baseline and 2, 6, 10, 22 and 46 weeks or the statement of patients were evaluated by Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) at baseline and 2, 6, 10, 22 and 46 weeks Previous primary outcome measure: Motor function measured using the ALS Functional Rating Scale-Revised (ALS-FRS-R) scale at baseline and 2, 6, 10, 22 and 46 weeks |
| Secondary outcome measures | Adverse events measured by a routine blood tests, blood biochemistry, coagulation function, hemolysis function, routine urine tests, 12 lead ECG, physical examination, vital signs, etc at baseline and 22 and 46 weeks |
| Overall study start date | 05/01/2018 |
| Overall study end date | 01/10/2021 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 40 |
| Participant inclusion criteria | 1. Male and female patients ≥18 years of age with sporadic or familial ALS or PD 2. If taking riluzole and/or edaravone, must be on a stable dose prior to screening |
| Participant exclusion criteria | 1. History of a clinically significant non-ALS or PD neurologic disorder 2. Inability to swallow capsules. 3. Human immunodeficiency virus (HIV) or current chronic/active infection with hepatitis C virus or hepatitis B virus 4. Women who are pregnant, planning to become pregnant, or are breastfeeding. 5. Use of non-invasive ventilation (NIV) or mechanical ventilation via tracheostomy, or any form of oxygen supplementation. 6. Current or anticipated need for a diaphragm pacing system (DPS). 7. Currently using glucocorticoids or have a history of regular systemic glucocorticoid use within the last 12 months. 8. Previous exposure or treatment with glucocorticoid receptor modulators or antagonists. |
| Recruitment start date | 05/01/2019 |
| Recruitment end date | 01/10/2020 |
Locations
Countries of recruitment
- China
Study participating centre
Beijing
100010
China
Sponsor information
Research organisation
Room C602G
289 Digital Peninsula
Shunfeng Industrial Park
No.2 Red Willow Road
Futian District
Shenzhen
518000
China
| Phone | +86 15919440001 |
|---|---|
| guocy@talengen-pharma.com |
Funders
Funder type
Research organisation
No information available
Results and Publications
| Intention to publish date | 01/02/2023 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from Ms Chunying Guo, guocy@talengen-pharma.com. The type of data that will be shared comprises a table showing the scoring records, clinical observation record forms, images, videotapes, and detection data. Dates of availability: 05/10/2023 to 05/10/2033. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | 27/01/2023 | No | No |
Additional files
Editorial Notes
14/11/2023: The following changes were made to the trial record:
1. The overall end date was changed from 10/10/2023 to 01/10/2021.
2. The target number of participants was changed from 20 to 40.
3. The recruitment end date was changed from 05/05/2023 to 01/10/2020.
4. The plain English summary was updated to reflect these changes.
09/11/2023: The following changes were made to the study record:
1. The condition was changed from 'Amyotrophic lateral sclerosis' to 'Amyotrophic lateral sclerosis and Parkinson’s disease' and all other fields were updated accordingly.
2. The primary outcome measure was updated.
29/03/2023: Internal review.
02/02/2023: The ethics details were updated.
27/01/2023: Trial's existence confirmed by the Ethics Committee of Beijing Chang’an Chinese and Western Integrated Medicine Hospital.
