Alzheimer Disease, Cognitive Impairment
Conditions
Brief summary
The primary purpose of this study is to determine whether sodium oligo-mannurarate capsule is effective and safe in the treatment of mild to moderate alzheimer' disease, and to determine the best therapeutic dose of sodium oligo-mannurarate capsule.
Detailed description
Alzheimer's disease is known for placing a great burden on caregivers which includes social, psychological, physical or economic aspects. Research indicates that the disease is associated with plaques and tangles in the brain. Currently used treatments offer a small symptomatic benefit. No treatments to delay or halt the progression of the disease are, as of yet, available. The investigators suppose sodium oligo-mannurarate capsule to be effective to halt the progression of the disease.
Interventions
DRUGSodium oligo-mannurarate 600mg
sodium oligo-mannurarate capsule 600mg twice a day for 24 weeks
sodium oligo-mannurarate capsule 900mg twice a day for 24 weeks
DRUGPlacebo
simulant of sodium oligo-mannurarate capsule
Sponsors
Shanghai Mental Health Center
Shanghai Greenvalley Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* At least primarily educated. * Accord with Probable Alzheimer disease of National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association(NINCDS-ADRDA)'s Criteria. * 10 points ≤ Minimum Mean-Square Error(MMSE) ≤ 24 points. * Hachinski ischemia scale \<4 points. * Hamilton depression scale ≤10 points. * Should have stable accompanying person, or at least contact 2 hours per day, 4 days per week with accompanying person. The accompanying person should help the patient throughout the trial. * Signed the information consent form.
Exclusion criteria
* Have been in other clinical trials within 30 days before this trial' start. * women during pregnancy or lactation. * Dementia caused by other diseases. * previous nervous system diseases. * Abnormal laboratory results. * Uncontrolled hypertension. * Unstable or serious diseases of heart, lung, liver, kidney and blood. * Visual or auditory handicap. * Significant focal lesions revealed by electronic computer X-ray tomography(CT) or magnetic resonance imaging(MRI) in one year before enrollment. * Alcohol abuse or drug abuse. * psychotic, including patients with serious depression. * Patients being in drug therapy of Alzheimer disease which cannot be stopped. * In treatment of heparin, Polysaccharide sulfate, mannose ester 3 weeks before the recruitment. * Investigator consider the patient cannot finish this trial for any reason. * Relatives or employees of the investigators, staff of the investigate centers, contract research organization and sponsor.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of Alzheimer's Disease Assessment Scale-cognitive Subscale(ADAS-cog)/12 After 24 Wks Treatment of Sodium Oligo-mannurarate Capsule | 24 weeks | Alzheimer's Disease Assessment Scale-cognitive Subscale(ADAS-cog)/12 is the most popular cognitive testing instrument used in clinical trials. It consists of 12 tasks measuring the disturbances of memory, language, praxis, attention and other cognitive abilities which are often referred to as the core symptoms of AD. The total score ranges 0-75, the higher score indicates more severity of the disease. Change after 24 wks treatment was calculated by the week 24 minus week 0 (baseline), and a negative change represents an improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change of Clinician's Interview-Based Impression of Change Plus(CIBIC-plus) After 24 Wks Treatment of Sodium Oligo-mannurarate Capsule | 24 weeks | Clinician's Interview-Based Impression of Change Plus(CIBIC-plus) is widely used in antidementia drug trials. It comprises Likert scales for disease severity and changes, and written accounts summarizing semistructured interviews evaluating behavior, cognition, and function. The results classified as 7 degrades as: Markedly improved, Moderately improved, Minimally improved, No change, Minimally worse, Moderately worse, and Markedly worse. |
| Change of Alzheimer's Disease Cooperative Study/Activities of Daily(ADCS-ADL) After 24 Wks Treatment of Sodium Oligo-mannurarate Capsule | 24 weeks | Alzheimer's Disease Cooperative Study/Activities of Daily (ADCS-ADL) is a scale assessed the daily activties of AD patients after interviewed the caregiver. The scale mainly assess the eating, walking, writing, bathing and reading, et al of the subject. The total score ranges 0-78, the higher score indicate improvement in daily activities. Change after 24 wks treatment was calculated by the week 24 minus week 0 (baseline), and a positive change represents an improvement. |
| Change of Neuropsychiatric Inventory(NPI) After 24 Wks Treatment of Sodium Oligo-mannurarate Capsule | 24 weeks | Neuropsychiatric Inventory (NPI) is a scale to obtain information on the presence of psychopathology in patient with brain disorders. The NPI was developed for application to patients with AD and other dementias, but it may be useful in the assessment of behavioral changes in other conditions. Twelve behavioral areas included in the NPI will be assessed in this trial: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety and elation/euphoria, et al. The total score ranges 0 to 120, the higher score indicates worse state of the AD patient. Change after 24wks treatmnt was calculated by the week 24 minus week 0 (baseline), and a negative change represents an improvement. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sodium Oligo-mannurarate 900mg Sodium oligo-mannurarate 900mg: sodium oligo-mannurarate capsule 900mg twice a day for 24 weeks | 83 |
| Sodium Oligo-mannurarate 600mg Sodium oligo-mannurarate 600mg: sodium oligo-mannurarate capsule 600mg twice a day for 24 weeks | 76 |
| Placebo Placebo: simulant of sodium oligo-mannurarate capsule | 83 |
| Total | 242 |
Baseline characteristics
| Characteristic | Sodium Oligo-mannurarate 900mg | Sodium Oligo-mannurarate 600mg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 70.39 years STANDARD_DEVIATION 8.51 | 70.26 years STANDARD_DEVIATION 8.4 | 70.34 years STANDARD_DEVIATION 8.13 | 70.33 years STANDARD_DEVIATION 8.24 |
| Sex: Female, Male Female | 50 Participants | 41 Participants | 52 Participants | 143 Participants |
| Sex: Female, Male Male | 33 Participants | 35 Participants | 31 Participants | 99 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 86 | 12 / 84 | 5 / 85 |
| serious Total, serious adverse events | 3 / 86 | 6 / 84 | 6 / 85 |
Outcome results
Primary
Change of Alzheimer's Disease Assessment Scale-cognitive Subscale(ADAS-cog)/12 After 24 Wks Treatment of Sodium Oligo-mannurarate Capsule
Alzheimer's Disease Assessment Scale-cognitive Subscale(ADAS-cog)/12 is the most popular cognitive testing instrument used in clinical trials. It consists of 12 tasks measuring the disturbances of memory, language, praxis, attention and other cognitive abilities which are often referred to as the core symptoms of AD. The total score ranges 0-75, the higher score indicates more severity of the disease. Change after 24 wks treatment was calculated by the week 24 minus week 0 (baseline), and a negative change represents an improvement.
Time frame: 24 weeks
Population: 85, 84, 86 patients were enrolled, and 2, 8 and 3 subjects were excluded from FAS in placebo, 600 mg and 900 mg group respectively. So the case No. ananlysed were 83, 76, 83 for placebo, 600 mg and 900 mg group respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sodium Oligo-mannurarate 900mg | Change of Alzheimer's Disease Assessment Scale-cognitive Subscale(ADAS-cog)/12 After 24 Wks Treatment of Sodium Oligo-mannurarate Capsule | -2.58 units on a scale | Standard Error 0.62 |
| Sodium Oligo-mannurarate 600mg | Change of Alzheimer's Disease Assessment Scale-cognitive Subscale(ADAS-cog)/12 After 24 Wks Treatment of Sodium Oligo-mannurarate Capsule | -1.39 units on a scale | Standard Error 0.75 |
| Placebo | Change of Alzheimer's Disease Assessment Scale-cognitive Subscale(ADAS-cog)/12 After 24 Wks Treatment of Sodium Oligo-mannurarate Capsule | -1.45 units on a scale | Standard Error 0.77 |
Secondary
Change of Alzheimer's Disease Cooperative Study/Activities of Daily(ADCS-ADL) After 24 Wks Treatment of Sodium Oligo-mannurarate Capsule
Alzheimer's Disease Cooperative Study/Activities of Daily (ADCS-ADL) is a scale assessed the daily activties of AD patients after interviewed the caregiver. The scale mainly assess the eating, walking, writing, bathing and reading, et al of the subject. The total score ranges 0-78, the higher score indicate improvement in daily activities. Change after 24 wks treatment was calculated by the week 24 minus week 0 (baseline), and a positive change represents an improvement.
Time frame: 24 weeks
Population: 85, 84, 86 patients were enrolled, and 2, 8 and 3 subjects were excluded from FAS in placebo, 600 mg and 900 mg group respectively. So the case No. ananlysed were 83, 76, 83 for placebo, 600 mg and 900 mg group respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sodium Oligo-mannurarate 900mg | Change of Alzheimer's Disease Cooperative Study/Activities of Daily(ADCS-ADL) After 24 Wks Treatment of Sodium Oligo-mannurarate Capsule | -0.49 units on a scale | Standard Error 0.91 |
| Sodium Oligo-mannurarate 600mg | Change of Alzheimer's Disease Cooperative Study/Activities of Daily(ADCS-ADL) After 24 Wks Treatment of Sodium Oligo-mannurarate Capsule | -0.47 units on a scale | Standard Error 0.88 |
| Placebo | Change of Alzheimer's Disease Cooperative Study/Activities of Daily(ADCS-ADL) After 24 Wks Treatment of Sodium Oligo-mannurarate Capsule | -1.06 units on a scale | Standard Error 0.85 |
Secondary
Change of Clinician's Interview-Based Impression of Change Plus(CIBIC-plus) After 24 Wks Treatment of Sodium Oligo-mannurarate Capsule
Clinician's Interview-Based Impression of Change Plus(CIBIC-plus) is widely used in antidementia drug trials. It comprises Likert scales for disease severity and changes, and written accounts summarizing semistructured interviews evaluating behavior, cognition, and function. The results classified as 7 degrades as: Markedly improved, Moderately improved, Minimally improved, No change, Minimally worse, Moderately worse, and Markedly worse.
Time frame: 24 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sodium Oligo-mannurarate 900mg | Change of Clinician's Interview-Based Impression of Change Plus(CIBIC-plus) After 24 Wks Treatment of Sodium Oligo-mannurarate Capsule | Markedly improved | 0 participants |
| Sodium Oligo-mannurarate 900mg | Change of Clinician's Interview-Based Impression of Change Plus(CIBIC-plus) After 24 Wks Treatment of Sodium Oligo-mannurarate Capsule | Moderately improved | 13 participants |
| Sodium Oligo-mannurarate 900mg | Change of Clinician's Interview-Based Impression of Change Plus(CIBIC-plus) After 24 Wks Treatment of Sodium Oligo-mannurarate Capsule | Minimally improved | 29 participants |
| Sodium Oligo-mannurarate 900mg | Change of Clinician's Interview-Based Impression of Change Plus(CIBIC-plus) After 24 Wks Treatment of Sodium Oligo-mannurarate Capsule | No change | 35 participants |
| Sodium Oligo-mannurarate 900mg | Change of Clinician's Interview-Based Impression of Change Plus(CIBIC-plus) After 24 Wks Treatment of Sodium Oligo-mannurarate Capsule | Moderately worse | 2 participants |
| Sodium Oligo-mannurarate 900mg | Change of Clinician's Interview-Based Impression of Change Plus(CIBIC-plus) After 24 Wks Treatment of Sodium Oligo-mannurarate Capsule | Markedly worse | 0 participants |
| Sodium Oligo-mannurarate 900mg | Change of Clinician's Interview-Based Impression of Change Plus(CIBIC-plus) After 24 Wks Treatment of Sodium Oligo-mannurarate Capsule | Minimally worse | 4 participants |
| Sodium Oligo-mannurarate 600mg | Change of Clinician's Interview-Based Impression of Change Plus(CIBIC-plus) After 24 Wks Treatment of Sodium Oligo-mannurarate Capsule | No change | 23 participants |
| Sodium Oligo-mannurarate 600mg | Change of Clinician's Interview-Based Impression of Change Plus(CIBIC-plus) After 24 Wks Treatment of Sodium Oligo-mannurarate Capsule | Markedly improved | 2 participants |
| Sodium Oligo-mannurarate 600mg | Change of Clinician's Interview-Based Impression of Change Plus(CIBIC-plus) After 24 Wks Treatment of Sodium Oligo-mannurarate Capsule | Markedly worse | 0 participants |
| Sodium Oligo-mannurarate 600mg | Change of Clinician's Interview-Based Impression of Change Plus(CIBIC-plus) After 24 Wks Treatment of Sodium Oligo-mannurarate Capsule | Moderately improved | 9 participants |
| Sodium Oligo-mannurarate 600mg | Change of Clinician's Interview-Based Impression of Change Plus(CIBIC-plus) After 24 Wks Treatment of Sodium Oligo-mannurarate Capsule | Moderately worse | 3 participants |
| Sodium Oligo-mannurarate 600mg | Change of Clinician's Interview-Based Impression of Change Plus(CIBIC-plus) After 24 Wks Treatment of Sodium Oligo-mannurarate Capsule | Minimally worse | 21 participants |
| Sodium Oligo-mannurarate 600mg | Change of Clinician's Interview-Based Impression of Change Plus(CIBIC-plus) After 24 Wks Treatment of Sodium Oligo-mannurarate Capsule | Minimally improved | 18 participants |
| Placebo | Change of Clinician's Interview-Based Impression of Change Plus(CIBIC-plus) After 24 Wks Treatment of Sodium Oligo-mannurarate Capsule | No change | 25 participants |
| Placebo | Change of Clinician's Interview-Based Impression of Change Plus(CIBIC-plus) After 24 Wks Treatment of Sodium Oligo-mannurarate Capsule | Markedly improved | 3 participants |
| Placebo | Change of Clinician's Interview-Based Impression of Change Plus(CIBIC-plus) After 24 Wks Treatment of Sodium Oligo-mannurarate Capsule | Minimally worse | 17 participants |
| Placebo | Change of Clinician's Interview-Based Impression of Change Plus(CIBIC-plus) After 24 Wks Treatment of Sodium Oligo-mannurarate Capsule | Moderately worse | 0 participants |
| Placebo | Change of Clinician's Interview-Based Impression of Change Plus(CIBIC-plus) After 24 Wks Treatment of Sodium Oligo-mannurarate Capsule | Minimally improved | 32 participants |
| Placebo | Change of Clinician's Interview-Based Impression of Change Plus(CIBIC-plus) After 24 Wks Treatment of Sodium Oligo-mannurarate Capsule | Moderately improved | 6 participants |
| Placebo | Change of Clinician's Interview-Based Impression of Change Plus(CIBIC-plus) After 24 Wks Treatment of Sodium Oligo-mannurarate Capsule | Markedly worse | 0 participants |
Secondary
Change of Neuropsychiatric Inventory(NPI) After 24 Wks Treatment of Sodium Oligo-mannurarate Capsule
Neuropsychiatric Inventory (NPI) is a scale to obtain information on the presence of psychopathology in patient with brain disorders. The NPI was developed for application to patients with AD and other dementias, but it may be useful in the assessment of behavioral changes in other conditions. Twelve behavioral areas included in the NPI will be assessed in this trial: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety and elation/euphoria, et al. The total score ranges 0 to 120, the higher score indicates worse state of the AD patient. Change after 24wks treatmnt was calculated by the week 24 minus week 0 (baseline), and a negative change represents an improvement.
Time frame: 24 weeks
Population: 85, 84, 86 patients were enrolled, and 2, 8 and 3 subjects were excluded from FAS in placebo, 600 mg and 900 mg group respectively. So the case No. ananlysed were 83, 76, 83 for placebo, 600 mg and 900 mg group respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sodium Oligo-mannurarate 900mg | Change of Neuropsychiatric Inventory(NPI) After 24 Wks Treatment of Sodium Oligo-mannurarate Capsule | -1.11 units on a scale | Standard Error 1.22 |
| Sodium Oligo-mannurarate 600mg | Change of Neuropsychiatric Inventory(NPI) After 24 Wks Treatment of Sodium Oligo-mannurarate Capsule | 0.24 units on a scale | Standard Error 0.83 |
| Placebo | Change of Neuropsychiatric Inventory(NPI) After 24 Wks Treatment of Sodium Oligo-mannurarate Capsule | -2.08 units on a scale | Standard Error 0.98 |