Multiple System Atrophy
Conditions
Keywords
multiple system atrophy, 3-n-butylphthalide
Brief summary
The present study aims to conduct a randomized controlled trial to evaluate the efficacy and safety of 3-n-Butylphthalide (NBP) in improving symptoms in patients with Multiple System Atrophy (MSA). The main questions it aims to answer are: 1. To evaluate whether NBP soft capsules, compared with placebo, alleviates the major clinical symptoms in patients with MSA. 2. Whether NBP application is safe to treat patients with MSA. In this trial, NBP will be compared with placebo (similar soft capsule without effective component of NBP) to demonstrate if NBP can alleviates MSA symptoms Participants of ENMSA will: 1. Take NBP or Placebo three times a day for 6 months 2. Be served with clinical visit four times for follow-up and tests 3. Keep a diary of drug application and symptom changes
Interventions
DRUG3-N-butylphthalide
3-n-Butylphthalide (NBP), also known as celery seed oil extract, is a lipid-soluble compound isolated from celery seeds. NBP was approved by the China Food and Drug Administration (CFDA) in 2002 for the treatment of acute ischemic stroke. NBP has demonstrated significant improvement in motor deficits and exhibited neuroprotective effects in animal models of various neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). For NBP used in ENMSA trial, its dosage form is soft capsule, containing 100mg NBP per capsule. Application frequency will be three times a day, 2 capsules each time.
Sponsors
Second Affiliated Hospital, School of Medicine, Zhejiang University
The Second Affiliated Hospital of Jiaxing University
Beijing Chao Yang Hospital
Huzhou Central Hospital
Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University
First Affiliated Hospital of Guangxi Medical University
Ningbo No.2 Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Participants are assigned to NBP group or Placebo group in parallel for the duration of the study
Eligibility
Sex/Gender
ALL
Age
30 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Meet a diagnosis for "clinically established MSA" according to the Movement Disorder Society (MDS) diagnostic criteria for multiple system atrophy revised in 2022, as assessed by a neurologist; 2. Patients aged between 30 and 80 years, within 5 years since the initial diagnosis of MSA, and with a life expectancy greater than 3 years; 3. Patients are not entirely dependent on a wheelchair or bedridden and are capable of cooperating with necessary assessments and examinations, including scale evaluations, magnetic resonance imaging (MRI), and PET-CT scans; 4. Patients must have been on a stable medication regimen (for a duration of at least one month) prior to the trial, which may include drugs for anti-Parkinson, anti-autonomic dysfunction, anti-anxiety/depression agents, and sleep aids
Exclusion criteria
1. Patients with a diagnosis confirmed by PET-CT or revised during follow-up to other diseases, such as idiopathic Parkinson's disease, progressive supranuclear palsy, corticobasal degeneration, dementia with Lewy bodies, or secondary parkinsonian syndromes. 2. Patients with a history of other major neurological disorders, including ischemic stroke, intracranial hemorrhage, epilepsy, encephalitis, or central nervous system demyelinating diseases; 3. Patients with a history of psychiatric disorders that may involve psychotic symptoms, such as schizophrenia, major depressive disorder, or dissociative -conversion disorders. 4. Patients with severe hepatic or renal impairment (alanine aminotransferase \[ALT\] or aspartate aminotransferase \[AST\] levels \>2 xULN; Estimated creatinine clearance \<30 mL/min; 5. Patients with a heamorrhage event within the past 3 months or a high bleeding risk; 6. Patients with a history of significant craniocerebral trauma or surgery; 7. Patients with severe cognitive impairment (Mini-Mental State Examination \[MMSE\] score \<24); 8. Patients with a history of malignancy or autoimmune diseases; 9. Patients with dysphagia due to severe medullary dysfunction or esophageal disorders, or those unable to comply with medication administration for other reasons; 10. Patients who are pregnant, lactating, or planning a pregnancy within the next year.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Main symptom control of MSA | Baseline; 1st, 3rd, 6th, 12th month after intervention initiation | Use sum score Movement Disorder Society-Unified Multiple System Atrophy Rating Scale(MDS-UMSARS; score range: 0-104; higher score means worse symptoms of MSA) part I+II to evaluate the effectiveness of main symptom control of MSA |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall symptom control of MSA | Baseline; 1st, 3rd, 6th, 12th month after intervention initiation | Use sub score of Movement Disorder Society-Unified Multiple System Atrophy Rating Scale(MDS-UMSARS; score range: 0-104; higher score means worse symptoms of MSA) to evaluate the overall effectiveness of main symptom control of MSA |
| Autonomic function of MSA | Baseline; 6th, 12th month after intervention initiation | Use Composite Autonomic Symptom Score 31 (COMPASS-31; score range: 0-100; higher score means worse autonomic symptoms of MSA) scale to evaluate autonomic symptoms of MSA |
| Depressive symptom of MSA | Baseline; 6th, 12th month after intervention initiation | Use Hamilton Depression Scale (HAMD; score range: 0-52; higher score means worse depressive symptoms of MSA) scale to evaluate depressive symptom of MSA |
| Cognitive function of MSA | Baseline; 6th, 12th month after intervention initiation | Use Mini-mental State Examination scale (MMSE; score range: 0-30; higher score means better cognitive function of MSA patients) to evaluate cognitive symptoms of MSA |
| Life quality of MSA | Baseline; 6th, 12th month after intervention initiation | Use Multiple System Atrophy-Quality of Life (MSA-QoL; score range: 0-160; higher score means worse life quality of MSA) scale to evaluate life quality of MSA patients |
| Safety of Butylphthalide application in MSA patients | through study completion, an average of 1 year | Monitoring the incidence of AE/SAE and MSA specific mortality rate during the trial |
| Anxiety symptoms of MSA | Baseline; 6th, 12th month after intervention initiation | Use Hamilton Anxiety scale (HAMA; score range: 0-56; higher score means worse anxiety symptoms of MSA) to evaluate anxiety symptoms of MSA |
| Advanced Cognitive function of MSA | Baseline; 6th, 12th month after intervention initiation | Use Montreal Cognitive Assessment (MoCA; score range: 0-30; higher score means better cognitive function of MSA) to evaluate cognitive symptoms of MSA |
Countries
China
Contacts
CONTACTJiali Pu, MD
PRINCIPAL_INVESTIGATORJiali Pu, MD
2nd Affiliated Hospital, School of Medicine, Zhejiang University, China
Outcome results
None listed