Nitrate Modulates Cognitive Impairment Via Oral Microbiota.

Study Overview
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Brief Summary
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Alcohol use is increasingly prevalent in modern society and is known to cause cognitive impairment and dysregulation of inflammatory responses. In the present study, the investigators want to perform a randomised controlled trials to test whether nitrate could change the oral microbiota and benefit the cognitive impairment in alcohol dependence patients. The investigators survey the oral bacterial communities in saliva samples of 70 alcohol dependent patients following 14 days of dietary inorganic nitrate (nitrate-rich beetroot juice,  750 mg NO3- /d) and placebo (nitrate-depleted beetroot juice,  1 mg NO3- /d) supplementation.

Official Title
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The Effect of Nitrate on Cognitive Function in Alcohol Dependence Patients and the Potential Microbiota Mechanism.

Conditions
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Microtia, Alcohol Dependence

Intervention / Treatment
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* Dietary Supplement: nitrate-rich beetroot juice
* Dietary Supplement: nitrate-depleted beetroot juice


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Han nationality Montreal Cognitive Assessment(MoCA) score >11 Diagnosis of alcohol dependence Exclusion Criteria: Past or current infectious disease Past or current heart, brain, liver, kidney, and other severe diseases Past or current metabolic diseases that can lead to abnormalities of the immune system, such as obesity (Body Mass Index > 30 kg/m2), diabetes, or rheumatoid arthritis Past or current neurodegenerative diseases, such as Parkinson's disease Use of steroidal and non-steroidal anti-inflammatory drugs, antibiotics, antioxidants, and immunosuppressive agents within two months of enrollment Use of probiotics and probiotics every day for the first two months before enrollment Previous or current DSM-IV diagnosis of schizophrenia, depression, anxiety disorder, bipolar disorder, mental retardation, dementia (excluding mild cognitive impairment, MCI), or substance dependence other than alcohol and nicotine Irregular eating habits that affect the oral flora (except alcohol) in the previous two months Current oral disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Male

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group N<br> | Dietary Supplement: nitrate-rich beetroot juice<br>* nitrate-rich beetroot juice,  750 mg NO3- /d<br>|
| Placebo Comparator: Group P<br> | Dietary Supplement: nitrate-depleted beetroot juice<br>* nitrate-depleted beetroot juice,  1 mg NO3- /d<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of cognitive function from baseline to post-intervention | Test by Cambridge Neuropsychological Test Automatic Battery，CANTAB | baseline and post-intervention(two weeks after baseline test) | 
| Changes of oral microbiota from baseline to post-intervention | Saliva samples were used to test the composition of microbiota by 16S RNA sequencing. | baseline and post-intervention(two weeks after baseline test) | 
| Changes of gut microbiota from baseline to post-intervention | Feces samples were used to test the composition of microbiota by 16S RNA sequencing. | baseline and post-intervention(two weeks after baseline test) | 
| Changes of nitrate and nitrite levels in serum from baseline to post-intervention | The collected serum samples were used to test the levels of nitrate and nitrite by High Performance Liquid Chromatography \ HPLC | baseline and post-intervention(two weeks after baseline test) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cytokine Interleukin-1b in serum | The collected serum samples were used to test the levels of IL-1b by Enzyme-Linked Immunosorbent Assay | baseline and post-intervention(two weeks after baseline test) | 
| Cytokine Interleukin-6 in serum | The collected serum samples were used to test the levels of IL-6 by Enzyme-Linked Immunosorbent Assay | baseline and post-intervention (two weeks after baseline test) | 
| Cytokine Interleukin-10 in serum | The collected serum samples were used to test the levels of IL-10 by Enzyme-Linked Immunosorbent Assay | baseline and post-intervention (two weeks after baseline test) | 
| Cytokine Tumor Necrosis Factor-a in serum | The collected serum samples were used to test the levels of TNF-a by Enzyme-Linked Immunosorbent Assay | baseline and post-intervention(two weeks after baseline test) | 
| The blood biochemical related parameters includes liver enzymes (alanine aminotransferase and aspartate aminotransferase) | The collected venous blood were sent to the department of clinical laboratory and the investigators recorded the laboratory report. | baseline and post-intervention (two weeks after baseline test) | 
| The blood biochemical related parameters blood fat (cholesterol, triglycerides, low density lipoprotein and high density lipoprotein | The collected venous blood were sent to the department of clinical laboratory and the investigators recorded the laboratory report. | baseline and post-intervention (two weeks after baseline test) | 
| Alcohol craving by Visual Analogue Scale（VAS） | Tested by Visual Analogue Scale（VAS） | baseline and post-intervention (two weeks after baseline test) | 
| Alcohol craving | Tested by Tested by Penn Alcohol Craving Scale（PACS) | baseline and post-intervention (two weeks after baseline test) | 
| Alcohol withdrawal assessment | Tested by Clinical Institute Withdrawal Assessment of Alcohol, revised（CIWA-AR） | baseline and post-intervention (two weeks after baseline test) | 
| Alcohol craving by Alcohol Urge Questionnaire | Tested by Alcohol Urge Questionnaire | baseline and post-intervention (two weeks after baseline test) | 
| depression | Test by Hamilton Depression Rating Scale | baseline and post-intervention (two weeks after baseline test) | 
| anxiety | Test by Hamilton Anxiety Rating Scale | baseline and post-intervention(two weeks after baseline test) | 
| Sleep Quality | Test by pittsburgh sleep quality index | baseline and post-intervention (two weeks after baseline test) | 
| blood pressure | Test by blood pressure monitor | baseline and post-intervention (two weeks after baseline test) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nitrate, oral microbiota, alcohol dependence