Effects of Pitavastatin on Insulin Sensitivity and Liver Fat

Not Applicable

Completed

• Conditions: Obesity; Fatty Liver, Nonalcoholic
• Interventions: Drug: pitavastatin; Other: PLACEBO

• Registration Number: NCT02290106
• Lead Sponsor: Massachusetts General Hospital

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-11-08
• Study First Submitted QC: 2014-11-08
• Study First Posted: 2014-11-13
• Study Start: 2015-03-02
• Primary Completion: 2018-04-30
• Study Completion: 2018-04-30
• Results First Submitted: 2019-03-22
• Status Verified: 2019-06
• Results First Submitted QC: 2019-06-12
• Last Update Submitted: 2019-06-12
• Results First Posted: 2019-07-02
• Last Update Posted: 2019-07-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 50

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pitavastatin	pitavastatin	pitavastatin 4mg daily by mouth for 6 months
Placebo	PLACEBO	Identical placebo 4mg by mouth daily for 6 months

Primary Outcome Measures

Name	Time	Method
Insulin-stimulated Glucose Uptake	6 months	insulin-stimulated glucose uptake measured by euglycemic hyperinsulinemic clamp
Liver Fat	6 months	liver fat content as measured by 1H-magnetic resonance spectroscopy

Secondary Outcome Measures

Name	Time	Method
Aspartate Aminotransferase (AST)	6 months	aspartate aminotransferase at 6 month timepoint
Hepatic Insulin Sensitivity	6 months	hepatic insulin sensitivity assessed by glucose infusion rate corrected for fluctuations in serum glucose ("M") during low-dose insulin clamp
Alanine Aminotransferase (ALT)	6 months	alanine aminotransferase at the 6 month timepoint
Hemoglobin A1c (HbA1c)	6 months
Quantitative Insulin Sensitivity Check Index (QUICKI)	6 months	quantitative insulin sensitivity check index (QUICKI) at 6 months. Measure = 1/((log(glucose in mg/dL) + log(insulin in uU/mL))

Trial Locations

Locations (1)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States