Evaluation of the Effect of Wismemo on Alzheimer's Dementia Patients

Evaluation of the Effect of Probiotic Supplementation on Cognitive, Emotional and Related Status on Alzheimer's Dementia Patients

The present studies demonstrated that pro-inflammation, systemic oxidative stress and dysfunction in the brain-gut microbiota axis were involved in Alzheimer's disease (AD) pathogenesis. These results implied the decreased regulation of inflammation-associated risk and microbiota in AD patients could provide the novel strategies for combating the disease. This study was designed to assess the addition of Wismemo in treatment of cholinesterase inhibitors (such as donepezil, rivastigmine, galantamine) in the AD patients.

Study Overview

• Status: Withdrawn
• Conditions: Alzheimer Disease
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Wismemo

Detailed Description

Previously studies have shown some probiotics could improve stress-related diseases such as anxiety, autism, depression and schizophrenia might be through regulating brain-gut microbiota axis, pro-inflammation and oxidative stress. Although recent clinical study indicated that mix-probiotics (containing Lactobacillus acidophilus, Lactobacillus casei, Bifidobacteria bifidum and Lactobacillus fermentum) consumption could improve the cognitive function of dementia patients.

In this clinical study, whether Genmont specific strain probiotics could improve the clinical syndromes and delay worsens in Alzheimer's dementia patients with regular treatment were clarified. A Randomized, double-blind, placebo-controlled clinical trial would be carried out. AD's patients with regular treatment are additive consumption multi-strain probiotic supplement (Wismemo). Half of participants will receive Wismeno and regular treatment in combination, while the other half will receive placebo and regular treatment in combination. To evaluate of the effect of probiotic supplementation on cognitive, emotional and related status on Alzheimer's dementia patients.

• Study Type: Interventional
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects with Alzheimer's Dementia. (According to the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association diagnostic criteria (NINCDS-ADRDA) and new criteria and guidelines to diagnose Alzheimer's disease were published in 2011 by the National Institute on Aging and Alzheimer's Association)
2. Subjects with administrating cholinesterase inhibitors, such as donepezil, rivastigmine, galantamine.
3. Subjects in age of 55-95 years old.

Exclusion Criteria:

1. Subjects are mixed dementia and vascular dementia.
2. Administration of probiotic dietary supplement 2 weeks before inclusion expect for yakult or yogurt.
3. Participation in other clinical trials.
4. Subjects with thyroid dysfunction.
5. Subjects are receiving cancer drugs.
6. Subjects are receiving immunosuppressant drugs.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Subjects received two placebo sachets per day	Dietary supplement: Placebo; placebo; Other Names: Regular treatment with placebo
Experimental: Probiotic; Subjects received two Wismemo sachets with 1x10^10 cfu/day	Dietary supplement: Wismemo; Multi-strain probiotic supplement includes Lactobacillus reuteri GMNL-89, Lactobacillus paracasei GMNL-133 and Lactobacillus plantarum GMNL-141.; Other Names: Regular treatment with Wismemo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mini-Mental State Examination (MMSE) for efficacy	Change in cognitive status was evaluated using the Mini-Mental State Examination (MMSE). MMSE will be assessed at baseline and after intervention. The maximum score is 30. If the scores are less than 24, it would be assessed to the mild dementia. If the scores are less than 16, it would be assessed to the severe dementia.	0, 3, 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neuropsychiatric Inventory (NPI) for efficacy and quality of life	Change from baseline in scores of psychosocial scale and caregiver distress was evaluated using the neuropsychiatric Inventory (NPI) by 12 items respectively. The 12 items include delusion, fantasy, depression, anxiety, etc., The maximum score of psychosocial scale is 144. The maximum score of caregiver distress is 60. Change in scores of total and each item will be assessed at baseline and after intervention.	0, 3, 6 months
Change from baseline in levels of peroxidation and antioxidant profiles (MDA and TAC)	Serum levels may possibly decrease peroxidation or increase antioxidant effects of probiotics.	0 and 6 months
Change from baseline in levels of inflammatory markers (IL-10,IL-6, IL-1 beta, TNF-alpha and TGF-beta)	Serum levels may possibly decrease inflammatory or increase anti-inflammatory effects of probiotics.	0 and 6 months
Change from baseline in levels of inflammatory markers (hs-CRP)	Serum levels may possibly decrease inflammatory effects of probiotics.	0 and 6 months
Change from baseline in levels of blood sugar (HbA1c)	Serum levels may possibly decrease high blood sugar effect of probiotics.	0 and 6 months
Change from baseline in levels of insulin resistance profile (FPG, insulin and HOMA-IR)	Serum levels may possibly decrease insulin resistance effect of probiotics.	0 and 6 months
Gut microbiota for efficacy	Stool samples at baseline and after intervention will be collected. Gut microbiota profile will be assessed.	0 and 6 months
Mini-Nutritional Assessment (MNA) for feasibility and efficacy	Change in Mini-Nutritional Assessment (MNA) MNA will be assessed at baseline and after intervention. The maximum score is 14. If the scores are 12-14, it would be assessed to normal malnutrition. If the scores are less than 12, it would be assessed to have the risk of malnutrition. If the scores are less than 8, it would be assessed to the malnutrition.	0, 3, 6 months
Defecation frequency and type for feasibility and efficacy	Change in Defecation frequency and type Defecation frequency and type will be assessed at baseline and after intervention.	0, 3, 6 months
Zarit's Caregiver Burden Scale for quality of life	Change in total scores of Zarit's Caregiver Burden Scale will be assessed at baseline and after intervention for caregiver stress. The maximum score is 48. The minimum score is 0. If the scores are 0-10, it would be assessed to no to mild burden. If the scores are 10-20, it would be assessed to mild to moderate burden. If the scores are greater than 20, it would be assessed to high burden.	0, 3, 6 months
Brief Symptom Rating Scale for quality of life	Change in total scores of Brief Symptom Rating Scale (BSRS-5) will be assessed at baseline and after intervention for caregiver stress. The maximum score is 24. The minimum score is 0. If the scores are 0-5, it would be assessed to good. If the scores are 6-9, it would be assessed to mild emotional distress. If the scores are 10-14, it would be assessed to moderate emotional distress. If the scores are greater than or equal t 15, it would be assessed to severe emotional distress.	0, 3, 6 months
Fatigue scale for quality of life	Change in total scores of Fatigue scale will be assessed at baseline and after intervention for caregiver stress. The maximum score is 63. The minimum score is 9.	0, 3, 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Drug Records for feasibility and efficacy	Drug Records including the dosage and frequency The major drugs including cholinesterase inhibitors, such as donepezil, rivastigmine, galantamine will be assessed at baseline and after intervention.	0, 3, 6 months
Adverse Events (AE) for feasibility and safety	Expected AE including constipation, diarrhea, flatulence and others gastrointestinal symptoms, unexpected or suspected adverse reaction will be assessed at baseline and after intervention. The AE will be reported by numbers of participants and ratio with different symptoms. And concern the AE of cholinesterase inhibitors with probiotic.	0, 3, 6 months
Change from baseline in levels of complete blood count and white blood cell differential count	To assess the safety after intervention using blood samples.	0 and 6 months
Change from baseline in levels of AST and ALT	To assess the liver toxicity after intervention using blood samples.	0 and 6 months
Change from baseline in levels of BUN, creatinine, microalbumin, GFR, ACR and urine routine examination	To assess the kidney toxicity after intervention using blood and urine samples.	0 and 6 months

Collaborators and Investigators

• Sponsor: GenMont Biotech Incorporation
• Collaborators: Chang Gung Memorial Hospital
• Investigators: Principal Investigator: Nai-Ching Chen, M.D., Chang Gung Memorial Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2020
• Primary Completion (Actual): February 11, 2020
• Study Completion (Actual): February 11, 2020

Study Registration Dates

• First Submitted: September 4, 2019
• First Submitted That Met QC Criteria: September 17, 2019
• First Posted (Actual): September 18, 2019

Study Record Updates

• Last Update Posted (Actual): February 13, 2020
• Last Update Submitted That Met QC Criteria: February 11, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Alzheimer's disease; Probiotics; Dementia; Intestinal microbiota; Chronic inflammation
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Tauopathies; Dementia; Alzheimer Disease
• Other Study ID Numbers: 201801746A3

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No