Nitrate Modulates Cognitive Impairment Via Oral Microbiota.

Alcohol Dependence Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05963659
• Other study ID #: 20230630
• Status: Recruiting
• Phase: N/A
• Start date: September 10, 2023
• Est. completion date: August 7, 2024

Study information

• Verified date: January 2024
• Source: Peking University Sixth Hospital
• Contact: Xiangxue li
• Phone: +8613719234046
• Email: 2011210552[@]bjmu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 70
• Est. completion date: August 7, 2024
• Est. primary completion date: August 7, 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Alcohol Dependence
• Alcoholism
• Microtia

Intervention

Dietary Supplement:
• nitrate-rich beetroot juice
nitrate-rich beetroot juice, ~750 mg NO3- /d
• nitrate-depleted beetroot juice
nitrate-depleted beetroot juice, ~1 mg NO3- /d

Locations

Country	Name	City	State
China	Anhui mental health center	Hefei	Anhui

Sponsors (1)

Lead Sponsor	Collaborator
Peking University Sixth Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Systolic and diastolic blood pressure	Test by blood pressure monitor	baseline and post-intervention (two weeks after baseline test)
Other	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)
Other	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)
Other	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)
Other	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)
Other	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)
Other	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)
Primary	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)
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)