Effects of Pitavastatin on Insulin Sensitivity and Liver Fat

NCT ID: NCT02290106

Last Updated: 2019-07-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-03-02
• Study Completion Date: 2018-04-30

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.

Conditions

Obesity; Fatty Liver, Nonalcoholic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Pitavastatin

pitavastatin 4mg daily by mouth for 6 months

Group Type: EXPERIMENTAL

pitavastatin

Intervention Type: DRUG

Placebo

Identical placebo 4mg by mouth daily for 6 months

Group Type: PLACEBO_COMPARATOR

PLACEBO

Intervention Type: OTHER

Interventions

pitavastatin

Intervention Type: DRUG

PLACEBO

Intervention Type: OTHER

Other Intervention Names

Livalo

Eligibility Criteria

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

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Takara Stanley

Assistant Professor of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Steven K Grinspoon, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Takara L Stanley, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Countries

United States

References

Braun LR, Feldpausch MN, Czerwonka N, Weiss J, Branch K, Lee H, Martinez-Salazar EL, Torriani M, Sponseller CA, Grinspoon SK, Stanley TL. Effects of Pitavastatin on Insulin Sensitivity and Liver Fat: A Randomized Clinical Trial. J Clin Endocrinol Metab. 2018 Nov 1;103(11):4176-4186. doi: 10.1210/jc.2018-01446.

Reference Type: DERIVED

PMID: 30239757 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2014p-002117

Identifier Type: -

Identifier Source: org_study_id