Are inorganic nitrates protective for fatty liver?

Not Applicable

• Conditions: Diseases of liver; Nutritional, Metabolic, Endocrine; Oral and Gastrointestinal, Diseases of liver, Metabolic and Endocrine, Metabolic disorders

• Registration Number: ISRCTN36524222
• Lead Sponsor: Cambridge University Hospitals NHS Foundation Trust

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-09-18
• Study Completion: 2020-09-01
• Last Update Posted: 1 November 2021

Recruitment & Eligibility

• Status: Stopped
• Sex: Male
• Target Recruitment: 30

Inclusion Criteria

Current participant inclusion criteria (as of 07/02/2018):
1. Men with clinical diagnosis of non-alcoholic steatohepatitis and a mild (F0-F2) fibrosis stage as predicted by a FIB-4 score < 2.67
2. Age between 30-55 years
3. BMI between 25-35
4. Triglycerides = 1.7 mmol/L

Previous participant inclusion criteria
1. Men with clinical diagnosis of non-alcoholic steatohepatitis and a mild (F0-F2) fibrosis stage as predicted by a FIB-4 score < 2.67
2. Age between 30-55 years
3. BMI between 25-35
4. Glycaemia > 5.5 mmol/L
5. Triglycerides = 1.7 mmol/L

Exclusion Criteria

1. Current participation in other interventional clinical trials (to avoid confounding with other study outcomes), observational studies are allowed
2. Other hepatic diseases: i.e alcoholic (> 21U/wk), viral and autoimmune hepatitis (AIH, PSC, PBC), genetic conditions (e.g. hemochromatosis), drug-induced hepatitis, etc.
3. History of chronic conditions that could influence the study outcomes such as
3.1. Anaemia (Hb< 11g/dL) or abnormal values in WBC, platelet count, or INR
3.2. Glomerular filtration rate lower than 60 mL/min/1.73m2 or diuretics
3.3. Active cancer and any diagnosis of malignant cancer in the last 5 years
3.4. Chronic Inflammatory disease (e.g. IBD, rheumatoid arthritis) in chronic treatment with NSAIDs/Corticosteroids
3.5. Type 1 diabetes
4. Treatments that could influence the study outcomes such as:
4.1. Anti-Diabetic medications (Metformin, TZDs, insulin)
4.2. Lipid-lowering agents (Fibrates/Omega3)
4.3. Nitrate-derived agents
4.4. Anti-acids
4.5. Beta-blockers
4.6. Weight loss medications (sibutramine, orlistat, rimonabant) and history of bariatric surgery (weight loss related changes in systemic metabolism)
4.7. Hormonal therapies (oestrogens, thyroxine, and progesterone)
4.8. Anti-psychiatric drugs (antidepressants, sedatives, antipsychotics)
4.9. Sildenafil
4.10. Anticoagulants

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<br> 1. The primary outcome will be assessed through the changes measured at baseline, 7, 35, 42 and 70 days and include:<br> 1.1. Plasma 3-aminoisobutyric acid which will be measured using liquid chromatography-mass spectrometry (LC-MS),<br> 1.2. Changes in gene expression and activity of the key metabolic transcription factors peroxisome-proliferator activated receptor 1 alpha and delta in peripheral blood mononuclear cells using reverse-transcription and quantitative polymerase chain reaction<br>

Secondary Outcome Measures

Name	Time	Method
<br> 1. The effect of nitrate supplementation on body composition measured using a bioelectrical impedance device at baseline, 7, 35, 42 and 70 days<br> 2. The effect of nitrate supplementation on plasma lipidome using LC-MS at baseline, 7, 35, 42 and 70 days<br> 3. The effect of nitrate supplementation on plasma and urine nitrate and polyphenols levels using mass spectrometry methods at baseline, 7, 35, 42 and 70 days<br>