Exploration of Medicine

From: Molecular targets regulating endoplasmic reticulum-mitochondria crosstalk for NAFLD treatment

Table 2. Clinical trials for the intervention of NAFLD

NCT number	Title	Intervention	Phase	Outcome measures
NCT01677325	The clinical trial of NAFLD treated by traditional Chinese medicine	Chinese herb Yiqi Sanju Formula (YQSJF)	I	Computed tomography (CT) ratio of liver/spleen
				BMI (body mass index) and insulin sensitivity homeostatic model assessment (HOMA) index
				Liver function
				Lipid profile and non-esterified fatty acid (NEFA)
				Adiponectin, leptin, IL-6, TNF, and hs-C-reactive protein (CRP)
NCT00230113	Effect of n-3 PUFA supplementation in NAFLD patients	n-3 fatty acid diet supplementation	II	Reduction of intrahepatic fat content as determined by magnetic resonance spectroscopy
				Change in lipid profile and serum aminotransferase levels
				Change in levels of proinflammatory cytokines
				Change in insulin resistance determined by HOMA
NCT04019561	A study to evaluate the safety and pharmacodynamic efficacy of MEDI0382 in obese subjects with NAFLD/NASH	MEDI0382, a peptide targeted on glucagon-like peptide-1 (GLP-1)	II	Assess the safety and tolerability of MEDI0382
				Change in hepatic fat, liver volume, and fat volume
				Change in visceral adipose tissue and subcutaneous adipose tissue
				Change in circulating markers of hepatic inflammation
				And others
NCT02098317	DHA and Vitamin D in children with biopsy-proven NAFLD	DHA plus Vitamin D	III	Improvement in NAFLD activity score (NAS) and safety
NCT02098317	DHA and Vitamin D in children with biopsy-proven NAFLD	DHA plus Vitamin D	III	Improvement of laboratory parameters of metabolic syndromes, such as lipids and gluco-insulinemic profile
NCT03970031	A study of MSDC-0602K to assess glycemic control and cardiovascular outcomes in patients with pre-T2D or T2D and NAFLD/NASH	MSDC-0602K, a modulator of the mitochondrial pyruvate carrier	III	Change in glycosylated hemoglobin A1c (HbA1c) from baseline to week 26
NCT03970031			III	Change in the weighted average of standardized AST, cytokeratin 18 (CK-18), and HbA1c values
NCT02973295	Silymarin in NAFLD	Silymarin, a flavonolignan extracted from the milk thistle [Silybum marianum (L.) Gaernt.]	IV	Change (Reduction) of parameters of liver steatosis defined by controlled attenuation parameter (CAP) and liver fibrosis defined by liver stiffness measurements (LSM) during the 6 months
				Change in liver enzymes in a period of 6 months
				Change in insulin resistance in a period of 6 months
				Change in lipidogram in a period of 6 months
NCT02564679	Sleeve gastrectomy in adolescents with complicated morbid obesity and NAFLD	Laparoscopic sleeve gastrectomy (LSG)	NA	Improvement of metabolic parameters
				Improvement of liver parameters
				Improvement of liver histology
NCT04049396	Berberine and NAFLD	Berberine, a chemical found in several plants such as European barberry and Oregon grape	NA	Change from baseline of ALT, AST, alkaline phosphatase (ALP), TC, fasting blood sugar (FBS), TG, LDL, and high-density lipoprotein (HDL)
NCT04073368	Study of the safety and tolerability of AXA1125 and AXA1957 in subjects with NAFLD	Dietary supplement AXA1125 or AXA1957	NA	Incidence of study product emergent adverse events (AEs) and serious adverse events (SAEs)
				Percent change in liver fat
				Change in HOMA-insulin resistance (HOMA-IR)
				Change in plasma glucose, insulin, ALT, and AST
NCT01680640	Investigation of synbiotic treatment in NAFLD	Synbiotic, a mixture of probiotics and prebiotics	NA	Change in biomarkers for NAFLD and change in liver fat
NCT01680640	Investigation of synbiotic treatment in NAFLD	Synbiotic, a mixture of probiotics and prebiotics	NA	Change in adipose tissue inflammation, satiety, and risk factors for T2D
NCT03737071	The effects of low carbohydrate diet on liver fat content and mitochondrial fluxes	Low carbohydrate diet	NA	Change in hepatic triglyceride content
				Change in hepatic mitochondrial flux
				Change in beta-hydroxybutyrate production rate
				Change in glucose production rate
NCT03193125	Effects of carnitine supplementation on liver mitochondria fatty acid processing	Dietary supplement of L-carnitine	NA	Change from baseline in liver mitochondrial fatty acid processing during high-fructose drink challenge
NCT03151798	Nutrient overload, insulin resistance, and hepatic mitochondrial dysfunction	Lifestyle treatment	NA	Liver mitochondrial gene expression
				Liver mitochondrial fat oxidation
				Histology to determine the amount of fibrosis in the liver
NCT02457702	Mitochondrial function in patients with severe liver disease	Orally administered labeled glycerol ([U-¹³C₃]glycerol)	NA	Detection of ¹³C in plasma glucose by nuclear magnetic resonance of a blood sample
NCT03587727	Hepatic fat content and mitochondrial flux in obese youth before and after bariatric surgery	Weight loss surgery or bariatric surgery	NA	Changes in hepatic mitochondrial function
				Changes in insulin resistance/pancreas/gastrointestinal hormones
				Changes in NAFLD status via tissue
NCT03480594	Effect of fatty liver on TCA cycle flux and the pentose phosphate pathway (HP FFF)	Hyperpolarized [¹³C]pyruvate injection	I	Bicarbonate/lactate ratio
				Labeled glycerol fraction
				The fraction of [U-¹³C]glycerol that has passed through mitochondrial pathways prior to gluconeogenesis and the fraction of glucose, derived from [U-¹³C]glycerol, that has passed through the pentose phosphate pathway
NCT02344186	Effects of liraglutide on endoplasmic (ER) stress in obese patients with T2D	Liraglutide, a GLP-1 receptor agonist	NA	Changes in unfolded protein response markers

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MY and CZ contributed conception, drafted the review, and contributed equally.

Conflicts of interest

The authors declare that they have no conflicts of interest.

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