Safety, Efficacy and Dose Titration of Sodium Oligo-mannurarate Capsule on Mild to Moderate Alzheimer's Disease

Phase II Study of Sodium Oligo-mannurarate Capsule on Mild to Moderate Alzheimer Disease

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.

Study Overview

• Status: Completed
• Conditions: Cognitive Impairment; Alzheimer Disease
• Intervention / Treatment: Drug: Sodium oligo-mannurarate 900mg; Drug: Placebo; Drug: Sodium oligo-mannurarate 600mg

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.

• Study Type: Interventional
• Enrollment (Actual): 255
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100005
      • Beijing Hospital
  • Chongqing
    • Chongqing, Chongqing, China, 400010
      • Chongqing Medical University Second Affiliated Hospital
    • Chongqing, Chongqing, China, 400038
      • The First Affliated Hospital of Third Military Medical University
    • Chongqing, Chongqing, China, 400042
      • The Third Affliated Hospital of Third Military Medical University
  • Guangdong
    • Guangzho, Guangdong, China, 510170
      • Guangzhou Brain Hospital
    • Guangzhou, Guangdong, China, 510120
      • Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
  • Hebei
    • Zhangjiakou, Hebei, China, 075000
      • The 251 Hospital of People's Liberation Army
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150001
      • The First Affliated Hospital of Harbin Medical University
  • Hubei
    • Wuhan, Hubei, China, 430070
      • Wuhan General Hospital of Guangzhou Military of People's Military Army
    • Wuhan, Hubei, China, 430077
      • Zhongnan Hospital of Wuhan University
  • Hunan
    • Changsha, Hunan, China, 410005
      • Hunan Provincial People's Hospital
  • Inner Mongolia
    • Baotou, Inner Mongolia, China, 014040
      • The Central Hospital of Baotou
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • The Affliated Brain Hospital of Nanjing Medical University
    • Wuxi, Jiangsu, China, 214151
      • Wuxi mental health center
  • Liaoning
    • Shenyang, Liaoning, China, 110001
      • The First Affliated Hospital of Chinese Medical University
  • Shandong
    • Jinan, Shandong, China, 250021
      • Shandong Provincial Hospital
    • Jinan, Shandong, China, 250012
      • Qilu Hospital of Shandong University
    • Jinan, Shandong, China, 250033
      • The Second Hospital of Shandong University
  • Shanghai
    • Shanghai, Shanghai, China, 200011
      • The Ninth Hospital, Shanghai Jiao Tong University school of Medicine
    • Shanghai, Shanghai, China, 200030
      • Shanghai Mental Health Center , Shanghai Jiao Tong University school of Medicine
  • Shanxi
    • Xi'an, Shanxi, China, 710038
      • Tangdu Hospital of The Forth Military Medical University of PLA
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital, West China School of Medicine Sichuan University
  • Tianjin
    • Tianjin, Tianjin, China, 300052
      • Tianjin Medical University General Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310016
      • Sir Run Run Shaw Hospital, Medical College of Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; simulant of sodium oligo-mannurarate capsule
Experimental: sodium oligo-mannurarate 900mg	Drug: Sodium oligo-mannurarate 900mg; sodium oligo-mannurarate capsule 900mg twice a day for 24 weeks; Other Names: Sodium oligo-mannurarate high dose
Experimental: sodium oligo-mannurarate 600mg	Drug: Sodium oligo-mannurarate 600mg; sodium oligo-mannurarate capsule 600mg twice a day for 24 weeks; Other Names: Sodium oligo-mannurarate low dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	24 weeks
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.	24 weeks
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.	24 weeks

Collaborators and Investigators

• Sponsor: Shanghai Greenvalley Pharmaceutical Co., Ltd.
• Collaborators: Shanghai Mental Health Center
• Investigators: Principal Investigator: Shifu Xiao, M.D., Shanghai Mental Health Center

Publications and helpful links

General Publications

• Wang T, Kuang W, Chen W, Xu W, Zhang L, Li Y, Li H, Peng Y, Chen Y, Wang B, Xiao J, Li H, Yan C, Du Y, Tang M, He Z, Chen H, Li W, Lin H, Shi S, Bi J, Zhou H, Cheng Y, Gao X, Guan Y, Huang Q, Chen K, Xin X, Ding J, Geng M, Xiao S. A phase II randomized trial of sodium oligomannate in Alzheimer's dementia. Alzheimers Res Ther. 2020 Sep 14;12(1):110. doi: 10.1186/s13195-020-00678-3.

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): August 1, 2013
• Study Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: September 30, 2011
• First Submitted That Met QC Criteria: October 13, 2011
• First Posted (Estimate): October 18, 2011

Study Record Updates

• Last Update Posted (Estimate): January 27, 2015
• Last Update Submitted That Met QC Criteria: January 25, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: 9712011-1