Role of Pioglitazone and Berberine in Treatment of Non-Alcoholic Fatty Liver Disease

NCT00633282 | Completed Phase 2 DMC

• 1 other identifier: 07JC14011
• Study Type: interventional
• Target: 184
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to evaluate the effects and safety of pioglitazone and berberine on the basis of lifestyle intervention to non-alcoholic fatty liver disease patients with impaired glucose regulation or type 2 diabetes mellitus.

Conditions

Nonalcoholic Fatty Liver Disease

Keywords

Nonalcoholic Fatty Liver Disease; Pioglitazone; Berberine; Impaired Glucose Metabolism

Outcome Measures

Primary Outcomes (1)

• Improved metabolic parameters(glucose, lipid, liver enzymes, etc.)

  improvement of the metabolic parameters, including serum glucose of OGTT, fasting glucose,2 hour glucose,area under the glucose curve and HbA1c,lipid profile（TC、TG、HDL-c、LDL-c、ApoA、ApoB、ApoE and Lpa），liver enzymes（ALT,AST,ALP,γ-GT）.

  16 weeks

Secondary Outcomes (3)

• liver fat content

  16 weeks

• serum insulin

  16 weeks

• the ratio of withdrawing because of inefficiency

  16 weeks

Study Arms (3)

Lifestyle intervention

EXPERIMENTAL

Life style intervention including aerobic exercise and reducing energy intake(-500kcal) without drug

Behavioral: Life style intervention

Life style intervention, pioglitazone

EXPERIMENTAL

Life style intervention with pioglitazone 15mg qd for 16 weeks

Behavioral: Life style intervention; Drug: pioglitazone

Life style intervention, berberine

EXPERIMENTAL

Life style intervention with berberine 0.5g tid for 16 weeks

Behavioral: Life style intervention; Drug: berberine

Interventions

Life style intervention BEHAVIORAL

calorie limited diet: to subtract 500 kcal from daily mean calorie intake when entering the treatment activity: medium intensity aerobic exercise for more than 150 min per week with heart rate around 50-70% of the maximal heart rate; or higher-intensity aerobic exercise for more than 90min per week with heart rate around 70% of the maximal heart rate

Also known as: calorie limited diet, aerobic exercise

Life style intervention, berberine; Life style intervention, pioglitazone; Lifestyle intervention

pioglitazone DRUG

pioglitazone tablet,15mg qd ,30 minutes before breakfast,for 16 weeks

Also known as: Actlns, PPAR agonist, Thiazolidinediones, insulin sensitizer

Life style intervention, pioglitazone

berberine DRUG

berberine tablet 0.5g tid,30 minutes before each meal,for 16 weeks

Also known as: traditional Chinese medicine, herb

Life style intervention, berberine

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have an age range between 18 to 65 years (inclusive).
• Patients with fatty liver confirmed by ultrasound.
• Patients must meet the criteria for impaired glucose regulation or type 2 diabetes mellitus (FPG ≥ 5.6 mmol/L and/or a two hour glucose value ≥ 7.8 mmol/L).
• Course of diabetic mellitus no more than 1 years
• Diabetic patients have not received anti-diabetic drugs, including insulin, biguanides, sulfonylureas, thiazolidinediones, Alpha-glucosidase inhibitors, or glinides for 4 weeks before the time of enrollment
• Patients have not received lipid-regulating drugs (statins, fibrates)for 4 weeks before the time of enrollment
• Blood pressure \< 160/100 mmHg,after receiving lifestyle therapy and effective anti-hypertensive drugs.
• Patients must stopped other drugs medications for four weeks prior to entering the treatment period, such as: silybin, ursodeoxycholic acid, Polyene Phosphatidylcholine, vitamin E, some herbs with effect of regulating lipid and protecting liver function, etc.
• Liver fat content(LFC) assessed by 1H MRS ≥ 13%(LFC was calculated by dividing the integral of the methylene groups in fatty acid chains of the hepatic triglycerides by the sum of methylene groups and water).

You may not qualify if:

• Any causes of chronic liver disease other than NAFLD (such as - but not restricted to - alcohol or drug abuse, medication, chronic hepatitis B or C, autoimmune, etc.);
• Patients with significantly impaired liver function: ALT or AST ≥ 2 times upper limit of normal;
• HBsAg (+) and/or HCV-Ab (+);
• Patients with type 1 diabetes mellitus or gestational diabetes or special type diabetes, and patients with BMI \< 22 Kg/m2;
• Course of diabetes more than 1 years;
• Diabetics patients who have taken or are taking oral glucose-lowering drugs or insulin;
• Diabetics patients with a HbA1c \> 7.5% on initial visit;
• Patients with severe diabetes complications (diabetes ketoacidosis, diabetes coma or with symptomatic of diabetes coma; dysfunction of nerve, retinopathy, dysfunction of kidney）;
• Patients with serum creatinine ≥ 1.5 mg/dL (133 umol/L);
• Patients with a history of clinically significant heart disease (myocardial infarct, heart failure, and or severe cardiac rhythm);
• Complicating severe infection, within 6 months after operation, severe trauma;
• Patients with excess alcohol consumption≥140g/week(male); ≥ 70g/week(female);
• Patients have participated other clinical trials within 24 weeks;
• Patients with a history of drug allergy to TZDs and berberine;
• Patients wth gestation or possible gestation or lactation, or males or females who expecting gestation during clinical trial;

Sponsors & Collaborators

• Xin Gao: lead
• Shanghai Jiao Tong University School of Medicine: collaborator
• Shanghai Municipal Science and Technology Commission: collaborator

Study Sites (3)

Endocrinology and Metabolism Department, Zhongshan Hospital, Fudan University,

Shanghai, Shanghai Municipality, 200032, China

Location

Department of Endocrinology and Metabolism,Shanghai Clinical Center of Diabetes,Shanghai Institute of Diabetes,The sixth people's Hospital Affiliated to Shanghai Jiaotong University

Shanghai, Shanghai Municipality, 200233, China

Location

Department of Endocrinology and Metabolism,The Fifth People's Hospital，Fudan University

Shanghai, Shanghai Municipality, 200240, China

Location

Related Publications (11)

• Bedogni G, Miglioli L, Masutti F, Tiribelli C, Marchesini G, Bellentani S. Prevalence of and risk factors for nonalcoholic fatty liver disease: the Dionysos nutrition and liver study. Hepatology. 2005 Jul;42(1):44-52. doi: 10.1002/hep.20734.

  PMID: 15895401 BACKGROUND

• Fan JG, Zhu J, Li XJ, Chen L, Li L, Dai F, Li F, Chen SY. Prevalence of and risk factors for fatty liver in a general population of Shanghai, China. J Hepatol. 2005 Sep;43(3):508-14. doi: 10.1016/j.jhep.2005.02.042.

  PMID: 16006003 BACKGROUND

• Miyazaki Y, Mahankali A, Wajcberg E, Bajaj M, Mandarino LJ, DeFronzo RA. Effect of pioglitazone on circulating adipocytokine levels and insulin sensitivity in type 2 diabetic patients. J Clin Endocrinol Metab. 2004 Sep;89(9):4312-9. doi: 10.1210/jc.2004-0190.

  PMID: 15356026 BACKGROUND

• Szapary PO, Bloedon LT, Samaha FF, Duffy D, Wolfe ML, Soffer D, Reilly MP, Chittams J, Rader DJ. Effects of pioglitazone on lipoproteins, inflammatory markers, and adipokines in nondiabetic patients with metabolic syndrome. Arterioscler Thromb Vasc Biol. 2006 Jan;26(1):182-8. doi: 10.1161/01.ATV.0000195790.24531.4f. Epub 2005 Nov 10.

  PMID: 16284192 BACKGROUND

• Shadid S, Stehouwer CD, Jensen MD. Diet/Exercise versus pioglitazone: effects of insulin sensitization with decreasing or increasing fat mass on adipokines and inflammatory markers. J Clin Endocrinol Metab. 2006 Sep;91(9):3418-25. doi: 10.1210/jc.2006-0015. Epub 2006 Jun 27.

  PMID: 16804048 BACKGROUND

• Yoneda M, Endo H, Nozaki Y, Tomimoto A, Fujisawa T, Fujita K, Yoneda K, Takahashi H, Saito S, Iwasaki T, Yamamoto S, Tsutsumi S, Aburatani H, Wada K, Hotta K, Nakajima A. Life style-related diseases of the digestive system: gene expression in nonalcoholic steatohepatitis patients and treatment strategies. J Pharmacol Sci. 2007 Oct;105(2):151-6. doi: 10.1254/jphs.fm0070063. Epub 2007 Oct 6.

  PMID: 17928738 BACKGROUND

• Kong W, Wei J, Abidi P, Lin M, Inaba S, Li C, Wang Y, Wang Z, Si S, Pan H, Wang S, Wu J, Wang Y, Li Z, Liu J, Jiang JD. Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. Nat Med. 2004 Dec;10(12):1344-51. doi: 10.1038/nm1135. Epub 2004 Nov 7.

  PMID: 15531889 BACKGROUND

• Yan H, Wu W, Chang X, Xia M, Ma S, Wang L, Gao J. Gender differences in the efficacy of pioglitazone treatment in nonalcoholic fatty liver disease patients with abnormal glucose metabolism. Biol Sex Differ. 2021 Jan 4;12(1):1. doi: 10.1186/s13293-020-00344-1.

  PMID: 33397443 DERIVED

• Ipsen EO, Madsen KS, Chi Y, Pedersen-Bjergaard U, Richter B, Metzendorf MI, Hemmingsen B. Pioglitazone for prevention or delay of type 2 diabetes mellitus and its associated complications in people at risk for the development of type 2 diabetes mellitus. Cochrane Database Syst Rev. 2020 Nov 19;11(11):CD013516. doi: 10.1002/14651858.CD013516.pub2.

  PMID: 33210751 DERIVED

• Chang X, Wang Z, Zhang J, Yan H, Bian H, Xia M, Lin H, Jiang J, Gao X. Lipid profiling of the therapeutic effects of berberine in patients with nonalcoholic fatty liver disease. J Transl Med. 2016 Sep 15;14:266. doi: 10.1186/s12967-016-0982-x.

  PMID: 27629750 DERIVED

• Yan HM, Xia MF, Wang Y, Chang XX, Yao XZ, Rao SX, Zeng MS, Tu YF, Feng R, Jia WP, Liu J, Deng W, Jiang JD, Gao X. Efficacy of Berberine in Patients with Non-Alcoholic Fatty Liver Disease. PLoS One. 2015 Aug 7;10(8):e0134172. doi: 10.1371/journal.pone.0134172. eCollection 2015.

  PMID: 26252777 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

Exercise; Pioglitazone; Thiazolidinediones; Berberine; Medicine, Chinese Traditional

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Berberine Alkaloids; Benzylisoquinolines; Alkaloids; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Medicine, East Asian Traditional; Medicine, Traditional; Complementary Therapies; Therapeutics

Study Officials

• Xin GAO, MD

  Fudan University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD. and Professor, Vice-President of Zhongshan Hospital, Director of Department of Endocrinology & Metabolism of Zhongshan Hospital Fudan University

Study Record Dates

• First Submitted: March 3, 2008
• First Posted: March 12, 2008
• Study Start: March 1, 2008
• Primary Completion: August 1, 2011
• Study Completion: August 1, 2011
• Last Updated: June 5, 2012

Record last verified: 2012-06

Locations

CN (3)