Effects of Pitavastatin on Insulin Sensitivity and Liver Fat

June 12, 2019 updated by: Takara Stanley, Massachusetts General Hospital
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.

Study Overview

Status

Completed

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pitavastatin
pitavastatin 4mg daily by mouth for 6 months
Other Names:
  • Livalo
Placebo Comparator: Placebo
Identical placebo 4mg by mouth daily for 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Insulin-stimulated Glucose Uptake
Time Frame: 6 months
insulin-stimulated glucose uptake measured by euglycemic hyperinsulinemic clamp
6 months
Liver Fat
Time Frame: 6 months
liver fat content as measured by 1H-magnetic resonance spectroscopy
6 months

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Steven K Grinspoon, MD, Massachusetts General Hospital
  • Principal Investigator: Takara L Stanley, MD, Massachusetts General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 2, 2015

Primary Completion (Actual)

April 30, 2018

Study Completion (Actual)

April 30, 2018

Study Registration Dates

First Submitted

November 8, 2014

First Submitted That Met QC Criteria

November 8, 2014

First Posted (Estimate)

November 13, 2014

Study Record Updates

Last Update Posted (Actual)

July 2, 2019

Last Update Submitted That Met QC Criteria

June 12, 2019

Last Verified

June 1, 2019

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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