Nitrate Modulates Cognitive Impairment Via Oral Microbiota.

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

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.

Study Overview

• Status: Recruiting
• Conditions: Alcohol Dependence; Microtia
• Intervention / Treatment: Dietary supplement: nitrate-rich beetroot juice; Dietary supplement: nitrate-depleted beetroot juice

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xiangxue Li; Phone Number: +8613719234046; Email: 2011210552@bjmu.edu.cn

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230022
      • Recruiting
      • Anhui Mental Health Center
      • Contact: Xiangxue Li; Phone Number: +8613719234046; Email: 2011210552@bjmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Han nationality
2. Montreal Cognitive Assessment(MoCA) score >11
3. Diagnosis of alcohol dependence

Exclusion Criteria:

1. Past or current infectious disease
2. Past or current heart, brain, liver, kidney, and other severe diseases
3. 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
4. Past or current neurodegenerative diseases, such as Parkinson's disease
5. Use of steroidal and non-steroidal anti-inflammatory drugs, antibiotics, antioxidants, and immunosuppressive agents within two months of enrollment
6. Use of probiotics and probiotics every day for the first two months before enrollment
7. 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
8. Irregular eating habits that affect the oral flora (except alcohol) in the previous two months
9. Current oral disease

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group N	Dietary supplement: nitrate-rich beetroot juice; nitrate-rich beetroot juice, ~750 mg NO3- /d
Placebo Comparator: Group P	Dietary supplement: nitrate-depleted beetroot juice; nitrate-depleted beetroot juice, ~1 mg NO3- /d

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of Delayed Match to Sample Percent Correct (all delays) from baseline to post-intervention	Test by DMS-PCAD (Delayed Match to Sample Percent Correct , all delays)	baseline and post-intervention(two weeks after baseline test)
Changes of Spatial Working Memory Between Errors from baseline to post-intervention	Test by SWM-BE (The Spatial Working Memory Between Errors )	baseline and post-intervention(two weeks after baseline test)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Delayed Match to Sample Percent Correct (0 seconds delay) from baseline to post-intervention	Test by Delayed Match to Sample Percent Correct (0 seconds delay)	baseline and post-intervention(two weeks after baseline test)
Changes of Delayed Match to Sample Percent Correct (4 seconds delay) from baseline to post-intervention	Test by Delayed Match to Sample Percent Correct (4 seconds delay)	baseline and post-intervention(two weeks after baseline test)
Changes of Delayed Match to Sample Percent Correct (12 seconds delay) from baseline to post-intervention	Test by Delayed Match to Sample Percent Correct (12 seconds delay)	baseline and post-intervention(two weeks after baseline test)
Changes of Spatial Working Memory errors 4 boxes from baseline to post-intervention	Test by The Spatial Working Memory errors 4 boxes	baseline and post-intervention(two weeks after baseline test)
Changes of Spatial Working Memory errors 6 boxes from baseline to post-intervention	Test by The Spatial Working Memory errors 6 boxes	baseline and post-intervention(two weeks after baseline test)
Changes of Spatial Working Memory errors 8 boxes from baseline to post-intervention	Test by The Spatial Working Memory errors 8 boxes	baseline and post-intervention(two weeks after baseline test)
Changes of Intra-Extra Dimensional Set Shift test Stages Completed from baseline to post-intervention	Test by The Intra-Extra Dimensional Set Shift test Stages Completed	baseline and post-intervention(two weeks after baseline test)
Changes of Intra-Extra Dimensional Completed Stage Errors from baseline to post-intervention	Test by The Intra-Extra Dimensional Completed Stage Errors	baseline and post-intervention(two weeks after baseline test)
Changes of Cambridge Gambling Task Risk Adjustment Merged: Risk adjustment from baseline to post-intervention	Test by Cambridge Gambling Task Risk Adjustment Merged: Risk adjustment	baseline and post-intervention(two weeks after baseline test)
Changes of Cambridge Gambling Decision Making Quality Total Merged from baseline to post-intervention	Test by Cambridge Gambling Decision Making Quality Total Merged	baseline and post-intervention(two weeks after baseline test)
Changes of Cambridge Gambling Delay Aversion Total from baseline to post-intervention	Test by Cambridge Gambling Delay Aversion Total	baseline and post-intervention(two weeks after baseline test)
Changes of Reaction Time Median Five-Choice Movement Time from baseline to post-intervention	Test by Reaction Time Median Five-Choice Movement Time	baseline and post-intervention(two weeks after baseline test)
Changes of Reaction Time Median Five-Choice Reaction Time from baseline to post-intervention	Test by Reaction Time Median Five-Choice Reaction Time	baseline and post-intervention(two weeks after baseline test)
Changes of Rapid Visual Information Processing test Probability of False Alarm from baseline to post-intervention	Test by the Rapid Visual Information Processing test Probability of False Alarm	baseline and post-intervention(two weeks after baseline test)
Changes of Rapid Visual Information Processing test A prime from baseline to post-intervention	Test by the Rapid Visual Information Processing test A prime	baseline and post-intervention(two weeks after baseline test)
Changes of Rapid Visual Information Processing test Median Response Latency from baseline to post-intervention	Test by the Rapid Visual Information Processing test Median Response Latency	baseline and post-intervention(two weeks after baseline test)
Changes of nitrate 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)
Changes of 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)

Other 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)
Systolic and diastolic blood pressure	Test by blood pressure monitor	baseline and post-intervention (two weeks after baseline test)

Collaborators and Investigators

• Sponsor: Peking University Sixth Hospital
• Investigators: Principal Investigator: Hongqiang Sun, Peking University Sixth Hospital; Study Chair: Liangjun Pang, Anhui mental health central

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2023
• Primary Completion (Estimated): August 7, 2024
• Study Completion (Estimated): August 7, 2024

Study Registration Dates

• First Submitted: June 30, 2023
• First Submitted That Met QC Criteria: July 26, 2023
• First Posted (Actual): July 27, 2023

Study Record Updates

• Last Update Posted (Estimated): January 24, 2024
• Last Update Submitted That Met QC Criteria: January 23, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: alcohol dependence; nitrate; oral microbiota
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Congenital Abnormalities; Otorhinolaryngologic Diseases; Ear Diseases; Alcoholism; Congenital Microtia
• Other Study ID Numbers: 20230630

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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