Effects of Pitavastatin on Insulin Sensitivity and Liver Fat

Obesity Clinical Trial

Official title:

Effects of Pitavastatin on Insulin Sensitivity and Liver Fat

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02290106
• Other study ID #: 2014p-002117
• Status: Completed
• Phase: N/A
• Start date: March 2, 2015
• Est. completion date: April 30, 2018

Study information

• Verified date: June 2019
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

HMG co-A reductase inhibitors, commonly called statins, are an effective treatment for dyslipidemia and atherosclerotic heart disease with proven mortality benefit. While the lipid-lowering effects of statins are well-known, other metabolic effects, including effects on glucose tolerance and ectopic fat distribution, are less completely understood. Recent studies have shown that some statins may increase the risk of diabetes. Further, research has suggested that statins may have some benefit in nonalcoholic fatty liver disease (NAFLD), a condition associated with obesity that includes increased fat in the liver (steatosis) and, in some cases, inflammation and hepatocellular damage (steatohepatitis). Pitavastatin, approved by the United States Food and Drug Administration (FDA) in 2009, is the most recent statin to enter the market. Unlike most statins, pitavastatin is not primarily metabolized through cytochrome P450 (CYP450), and thus has reduced potential for interactions with other medications that are metabolized by CYP450. Previous studies have suggested that pitavastatin may be neutral to glucose homeostasis and may improve hepatic lipid. Neither of these effects has been proven definitively, however, and the current proposal aims to characterize in detail the effects of pitavastatin on glucose homeostasis, hepatic steatosis, and steatohepatitis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: April 30, 2018
• Est. primary completion date: April 30, 2018
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 40 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Men age 40-65yo

2. BMI = 27kg/m2 and waist circumference =102cm, high probability risk factors for NAFLD

3. At least one of the following indicating insulin resistance: Fasting glucose =100mg/dL and <126mg/dL, HOMA-IR >2.0, and/or 2 hour glucose =140mg/dL and <200mg/dL following standard glucose tolerance test.

4. 10-year cardiovascular disease risk =5% by American Heart Association(AHA)/American College of Cardiology (ACC) Pooled Cohort Equations CV Risk Calculator or LDL = 100mg/dL

5. No use of any statin within 1 year of study entry and not being actively considered for statin therapy by a treating provider.

Exclusion Criteria:

1. Diagnosis of diabetes or use of anti-diabetic medications.

2. Use of erythromycin, rifampin, cyclosporin, colchicine, or gemfibrozil.

3. Use of statin therapy within 1 year prior to study entry as above. Use of any other lipid-modifying therapy (including fish oil, fibrates, niacin, gemfibrozil) within 6 months of study entry.

4. Contraindication to statin therapy.

5. Creatinine > upper limit of normal or known renal disease

6. AST or ALT > 3 times the upper limit of normal

7. hemoglobin < 10g/dL

8. Contraindication to undergoing a magnetic resonance scan.

9. Atherosclerotic cardiovascular disease or low-density lipoprotein cholesterol (LDL-C) = 190mg/dL.

10. Triglyceride =500mg/dL

Related Conditions & MeSH terms

• Fatty Liver
• Fatty Liver, Nonalcoholic
• Hypersensitivity
• Insulin Resistance
• Non-alcoholic Fatty Liver Disease
• Obesity

Intervention

Drug:
• pitavastatin

Other:
• PLACEBO

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Insulin-stimulated Glucose Uptake	insulin-stimulated glucose uptake measured by euglycemic hyperinsulinemic clamp	6 months
Primary	Liver Fat	liver fat content as measured by 1H-magnetic resonance spectroscopy	6 months
Secondary	Alanine Aminotransferase (ALT)	alanine aminotransferase at the 6 month timepoint	6 months
Secondary	Aspartate Aminotransferase (AST)	aspartate aminotransferase at 6 month timepoint	6 months
Secondary	Hepatic Insulin Sensitivity	hepatic insulin sensitivity assessed by glucose infusion rate corrected for fluctuations in serum glucose ("M") during low-dose insulin clamp	6 months
Secondary	Hemoglobin A1c (HbA1c)		6 months
Secondary	Quantitative Insulin Sensitivity Check Index (QUICKI)	quantitative insulin sensitivity check index (QUICKI) at 6 months. Measure = 1/((log(glucose in mg/dL) + log(insulin in uU/mL))	6 months