Effects of Bifidobacterium Longum OLP-01 Supplement on Cognitive Function, Exercise Performance, Nutritional Status and Gut Microbiota in Stroke Patients

Study Overview
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Brief Summary
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Stroke is a syndrome of acute, focal neurological deficit attributed to vascular injury of the central nervous system. It was the 2nd leading cause of death worldwide and accompanied by high disability rate also increases the social burden.Our research is to investigate the effects of intervention with Bifidobacterium longum OLP-01 on cognitive function, exercise performance, nutritional status and gut microbiota in stroke patients. Study population: We will recruit 120 stroke patients and the inclusion criteria are: (1) Aged 20-75 years old, (2) Diagnosed with stroke more than 3 months, (3) Undergoing outpatient rehabilitation and the condition is stable. The exclusion criteria are: (1) Aphasia, dementia or depression, (2) BMI ≥ 35 kg/m2, (3) Cancer treatment in 3 months, (4) Some severe disease may interfere patients to join the study, (5) Failed to cooperate the examination and treatment because of emotion or mental condition. Study design: A two-arm single-blind randomized controlled clinical trial will be performed for 12 weeks and the subjects will be divided in to 2 groups: (1) placebo group, (2) supplement group. Subjects were asked to supplement with either 2 × 1010 colony-forming unit (CFU) of Bifidobacterium longum OLP-01 powder per day or placebo for 12 weeks. Medical history, drug use and life style questionnaires were giving before intervention. Outcomes will be assess in week 0 and week 12 during intervention. 3. Outcome assessment: Anthropometry data: height, weight, body mass index, waist circumference, mid-upper arm circumference, hip circumference, calf circumference, waist to hip ratio. Body composition: muscle mass, body fat, basal metabolic rate. Clinical data: blood pressure, stroke related characteristics. Blood biochemistry: A. Nutritional status: albumin, prealbumin, transferrin. B. Glycemic profiles: fasting blood glucose, glycated hemoglobin A1c (HbA1c). C. Lipid profiles: total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG). D. Complete blood counts: white blood cells (WBC), red blood cells (RBC), hemoglobin (HB), platelet count (PLT), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC). E. WBC differential counts: neutrophils (NEUT), lymphocytes (LYM), monocytes (MONO), eosinophils (EOS), basophils (BASO). F. C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor alpha (TNF-α). Gut microbiota: relative abundance, α-diversity, β-diversity. Nutritional status: 3-day dietary record, mini-nutritional assessment (MNA). Cognitive function: Montreal cognitive assessment (MoCA), trail-making test A and B (TMT A and B), Stroop color naming test. Exercise performance: timed up and go test (TUGT), 6-min walking test. The purpose of the study is to investigate the intervention of Bifidobacterium longum OLP-01 supplement on cognitive function, physiological performance, nutritional status, and gut microbiota in stroke patients.

Official Title
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Effects of Bifidobacterium Longum OLP-01 Supplement on Cognitive Function, Exercise Performance, Nutritional Status and Gut Microbiota in Stroke Patients

Conditions
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Stroke

Intervention / Treatment
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* Dietary Supplement: Bifidobacterium longum OLP-01
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Aged 20-75 years old Diagnosed with stroke more than 3 months Undergoing outpatient rehabilitation and the condition is stable Exclusion criteria Aphasia, dementia or depression BMI ≥ 35 kg/m2 Cancer treatment in 3 months Some severe disease may interfere patients to join the study Failed to cooperate the examination and treatment because of emotion or mental condition.

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo group<br>Subjects in placebo group will treat with placebo. | Other: Placebo<br>* Subjects in placebo group will supplement with placebo powder per day for 12 weeks.<br>|
| Experimental: Supplement group<br>Subjects in supplement group will treat with Bifidobacterium longum OLP-01. | Dietary Supplement: Bifidobacterium longum OLP-01<br>* Bifidobacterium longum OLP-01 is one of probiotics. Subjects in OLP-01 group will supplement with either 2 × 1010 colony-forming unit (CFU) of Bifidobacterium longum OLP-01 powder per day for 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montreal cognitive assessment (MoCA) | Cognitive function | Week 0 | 
| Montreal cognitive assessment (MoCA) | Cognitive function | Week 12 | 
| Montreal cognitive assessment (MoCA) (change) | Cognitive function | Change from week 0 to week 12 | 
| Trail-making test A and B (TMT A and B) | Cognitive function | Week 0 | 
| Trail-making test A and B (TMT A and B) | Cognitive function | Week 12 | 
| Trail-making test A and B (TMT A and B) (change) | Cognitive function | Change from week 0 to week 12 | 
| Stroop color naming test | Cognitive function | Week 0 | 
| Stroop color naming test | Cognitive function | Week 12 | 
| Stroop color naming test (change) | Cognitive function | Change from week 0 to week 12 | 
| Timed up and go test (TUGT) | Exercise performance | Week 0 | 
| Timed up and go test (TUGT) | Exercise performance | Week 12 | 
| Timed up and go test (TUGT) (change) | Exercise performance | Change from week 0 to week 12 | 
| 6-min walking test | Exercise performance | Week 0 | 
| 6-min walking test | Exercise performance | Week 12 | 
| 6-min walking test (change) | Exercise performance | Change from week 0 to week 12 | 
| Albumin | Nutritional Status | Week 0 | 
| Albumin | Nutritional Status | Week 12 | 
| Albumin (change) | Nutritional Status | Change from week 0 to week 12 | 
| Pre-albumin | Nutritional Status | Week 0 | 
| Pre-albumin | Nutritional Status | Week 12 | 
| Pre-albumin (change) | Nutritional Status | Change from week 0 to week 12 | 
| Transferrin | Nutritional Status | Week 0 | 
| Transferrin | Nutritional Status | Week 12 | 
| Transferrin (change) | Nutritional Status | Change from week 0 to week 12 | 
| 3-day dietary record | Nutritional Status | Week 0 | 
| 3-day dietary record | Nutritional Status | Week 12 | 
| 3-day dietary record (change) | Nutritional Status | Change from week 0 to week 12 | 
| Mini-nutritional assessment (MNA) | Nutritional Status | Week 0 | 
| Mini-nutritional assessment (MNA) | Nutritional Status | Week 12 | 
| Mini-nutritional assessment (MNA) (change) | Nutritional Status | Change from week 0 to week 12 | 
| Relative abundance | Gut microbiota Use the 16s RNA sequencing to conduct the next generation sequencing (NGS) measure the relative abundance, including the phylum, class, family, genus. | Week 0 | 
| Relative abundance | Gut microbiota Use the 16s RNA sequencing to conduct the next generation sequencing (NGS) measure the relative abundance, including the phylum, class, family, genus. | Week 12 | 
| α-diversity | Gut microbiota | Week 0 | 
| α-diversity | Gut microbiota | Week 12 | 
| β-diversity | Gut microbiota | Week 0 | 
| β-diversity | Gut microbiota | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Height | Anthropometry data | Week 0 | 
| Height | Anthropometry data | Week 12 | 
| Height (change) | Anthropometry data | Change from week 0 to week 12 | 
| Weight | Anthropometry data | Week 0 | 
| Weight | Anthropometry data | Week 12 | 
| Weight (change) | Anthropometry data | Change from week 0 to week 12 | 
| Body mass index (BMI) | Anthropometry data Weight and height will be combined to report BMI in kg/m^2 | Week 0 | 
| Body mass index (BMI) | Anthropometry data Weight and height will be combined to report BMI in kg/m^2 | Week 12 | 
| Body mass index (BMI) (change) | Anthropometry data Weight and height will be combined to report BMI in kg/m^2 | Change from week 0 to week 12 | 
| Waist circumference | Anthropometry data | Week 0 | 
| Waist circumference | Anthropometry data | Week 12 | 
| Waist circumference (change) | Anthropometry data | Change from week 0 to week 12 | 
| Mid-upper arm circumference | Anthropometry data | Week 0 | 
| Mid-upper arm circumference | Anthropometry data | Week 12 | 
| Mid-upper arm circumference (change) | Anthropometry data | Change from week 0 to week 12 | 
| Hip circumference | Anthropometry data | Week 0 | 
| Hip circumference | Anthropometry data | Week 12 | 
| Hip circumference (change) | Anthropometry data | Change from week 0 to week 12 | 
| Calf circumference | Anthropometry data | Week 0 | 
| Calf circumference | Anthropometry data | Week 12 | 
| Calf circumference (change) | Anthropometry data | Change from week 0 to week 12 | 
| Waist to hip ratio | Anthropometry data Waist circumference and hip circumference will be combined to report waist to hip ratio | Week 0 | 
| Waist to hip ratio | Anthropometry data Waist circumference and hip circumference will be combined to report waist to hip ratio | Week 12 | 
| Waist to hip ratio (change) | Anthropometry data Waist circumference and hip circumference will be combined to report waist to hip ratio | Change from week 0 to week 12 | 
| Muscle mass | Body composition | Week 0 | 
| Muscle mass | Body composition | Week 12 | 
| Muscle mass (change) | Body composition | Change from week 0 to week 12 | 
| Body fat | Body composition | Week 0 | 
| Body fat | Body composition | Week 12 | 
| Body fat (change) | Body composition | Change from week 0 to week 12 | 
| Basal metabolic rate | Body composition | Week 0 | 
| Basal metabolic rate | Body composition | Week 12 | 
| Basal metabolic rate (change) | Body composition | Change from week 0 to week 12 | 
| Blood pressure | Clinical data | Week 0 | 
| Blood pressure | Clinical data | Week 12 | 
| Blood pressure (change) | Clinical data | Change from week 0 to week 12 | 
| Stroke related characteristics (including the time since stroke diagnosed, side of lesion, stroke type, use of aid) | Stroke related characteristics would collect form clinical data or ask form subjects directly | Week 0 | 
| Stroke related characteristics (including the time since stroke diagnosed, side of lesion, stroke type, use of aid) | Stroke related characteristics would collect form clinical data or ask form subjects directly | Week 12 | 
| Medical history, drug use and life style questionnaires | Clinical data This questionnaires including 3 parts (medical history, drug use and life style). Medical history and drug use will write by subjects. Life style (e.g. smocking habit, exercise frequency) will ask the subjects. | Week 0 | 
| Medical history, drug use and life style questionnaires | Clinical data This questionnaires including 3 parts (medical history, drug use and life style). Medical history and drug use will write by subjects. Life style (e.g. smocking habit, exercise frequency) will ask the subjects. | Week 12 | 
| Fasting blood glucose | Blood biochemistry | Week 0 | 
| Fasting blood glucose | Blood biochemistry | Week 12 | 
| Fasting blood glucose (change) | Blood biochemistry | Change from week 0 to week 12 | 
| Glycated hemoglobin A1c (HbA1c) | Blood biochemistry | Week 0 | 
| Glycated hemoglobin A1c (HbA1c) | Blood biochemistry | Week 12 | 
| Glycated hemoglobin A1c (HbA1c) (change) | Blood biochemistry | Change from week 0 to week 12 | 
| Total cholesterol (TC) | Blood biochemistry | Week 0 | 
| Total cholesterol (TC) | Blood biochemistry | Week 12 | 
| Total cholesterol (TC) (change) | Blood biochemistry | Change from week 0 to week 12 | 
| High density lipoprotein cholesterol (HDL-C) | Blood biochemistry | Week 0 | 
| High density lipoprotein cholesterol (HDL-C) | Blood biochemistry | Week 12 | 
| High density lipoprotein cholesterol (HDL-C) (change) | Blood biochemistry | Change from week 0 to week 12 | 
| Low density lipoprotein cholesterol (LDL-C) | Blood biochemistry | Week 0 | 
| Low density lipoprotein cholesterol (LDL-C) | Blood biochemistry | Week 12 | 
| Low density lipoprotein cholesterol (LDL-C) (change) | Blood biochemistry | Change from week 0 to week 12 | 
| Triglycerides (TG) | Blood biochemistry | Week 0 | 
| Triglycerides (TG) | Blood biochemistry | Week 12 | 
| Triglycerides (TG) (change) | Blood biochemistry | Change from week 0 to week 12 | 
| White blood cells (WBC) | Blood biochemistry | Week 0 | 
| White blood cells (WBC) | Blood biochemistry | Week 12 | 
| White blood cells (WBC) (change) | Blood biochemistry | Change from week 0 to week 12 | 
| Red blood cells (RBC) | Blood biochemistry | Week 0 | 
| Red blood cells (RBC) | Blood biochemistry | Week 12 | 
| Red blood cells (RBC) (change) | Blood biochemistry | Change from week 0 to week 12 | 
| Hemoglobin (HB) | Blood biochemistry | Week 0 | 
| Hemoglobin (HB) | Blood biochemistry | Week 12 | 
| Hemoglobin (HB) (change) | Blood biochemistry | Change from week 0 to week 12 | 
| Platelet count (PLT) | Blood biochemistry | Week 0 | 
| Platelet count (PLT) | Blood biochemistry | Week 12 | 
| Platelet count (PLT) (change) | Blood biochemistry | Change from week 0 to week 12 | 
| Hematocrit (HCT) | Blood biochemistry | Week 0 | 
| Hematocrit (HCT) | Blood biochemistry | Week 12 | 
| Hematocrit (HCT) (change) | Blood biochemistry | Change from week 0 to week 12 | 
| Mean corpuscular volume (MCV) | Blood biochemistry | Week 0 | 
| Mean corpuscular volume (MCV) | Blood biochemistry | Week 12 | 
| Mean corpuscular volume (MCV) (change) | Blood biochemistry | Change from week 0 to week 12 | 
| Mean corpuscular hemoglobin (MCH) | Blood biochemistry | Week 0 | 
| Mean corpuscular hemoglobin (MCH) | Blood biochemistry | Week 12 | 
| Mean corpuscular hemoglobin (MCH) (change) | Blood biochemistry | Change from week 0 to week 12 | 
| Mean corpuscular hemoglobin concentration (MCHC) | Blood biochemistry | Week 0 | 
| Mean corpuscular hemoglobin concentration (MCHC) | Blood biochemistry | Week 12 | 
| Mean corpuscular hemoglobin concentration (MCHC) (change) | Blood biochemistry | Change from week 0 to week 12 | 
| Neutrophils (NEUT) | Blood biochemistry (WBC counts) | Week 0 | 
| Neutrophils (NEUT) | Blood biochemistry (WBC counts) | Week 12 | 
| Neutrophils (NEUT) | Blood biochemistry (WBC counts) | Change from week 0 to week 12 | 
| Lymphocytes (LYM) | Blood biochemistry (WBC counts) | Week 0 | 
| Lymphocytes (LYM) | Blood biochemistry (WBC counts) | Week 12 | 
| Lymphocytes (LYM) | Blood biochemistry (WBC counts) | Change from week 0 to week 12 | 
| Monocytes (MONO) | Blood biochemistry (WBC counts) | Week 0 | 
| Monocytes (MONO) | Blood biochemistry (WBC counts) | Week 12 | 
| Monocytes (MONO) | Blood biochemistry (WBC counts) | Change from week 0 to week 12 | 
| Eosinophils (EOS) | Blood biochemistry (WBC counts) | Week 0 | 
| Eosinophils (EOS) | Blood biochemistry (WBC counts) | Week 12 | 
| Eosinophils (EOS) | Blood biochemistry (WBC counts) | Change from week 0 to week 12 | 
| Basophils (BASO) | Blood biochemistry (WBC counts) | Week 0 | 
| Basophils (BASO) | Blood biochemistry (WBC counts) | Week 12 | 
| Basophils (BASO) | Blood biochemistry (WBC counts) | Change from week 0 to week 12 | 
| Interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-α) | Blood biochemistry (cytokines) | Week 0 | 
| Interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-α) | Blood biochemistry (cytokines) | Week 12 | 
| Interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-α) (change) | Blood biochemistry (cytokines) | Change from week 0 to week 12 | 
| C-reactive protein (CRP) | Blood biochemistry | Week 0 | 
| C-reactive protein (CRP) | Blood biochemistry | Week 12 | 
| C-reactive protein (CRP) (change) | Blood biochemistry | Change from week 0 to week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bifidobacterium longum OLP-01, Stroke, Cognitive function, Exercise performance, Nutritional status, Gut microbiota