Effects of Pitavastatin on Insulin Sensitivity and Liver Fat

NCT02290106 | Completed Results

• 1 other identifier: 2014p-002117
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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

Keywords

obesity; insulin sensitivity; statin (HMG-CoA Reductase Inhibitor); fatty liver

Outcome Measures

Primary Outcomes (2)

• Insulin-stimulated Glucose Uptake

  insulin-stimulated glucose uptake measured by euglycemic hyperinsulinemic clamp

  6 months

• Liver Fat

  liver fat content as measured by 1H-magnetic resonance spectroscopy

  6 months

Secondary Outcomes (5)

• Alanine Aminotransferase (ALT)

  6 months

• Aspartate Aminotransferase (AST)

  6 months

• Hepatic Insulin Sensitivity

  6 months

• Hemoglobin A1c (HbA1c)

  6 months

• Quantitative Insulin Sensitivity Check Index (QUICKI)

  6 months

Study Arms (2)

Pitavastatin

EXPERIMENTAL

pitavastatin 4mg daily by mouth for 6 months

Drug: pitavastatin

Placebo

PLACEBO COMPARATOR

Identical placebo 4mg by mouth daily for 6 months

Other: PLACEBO

Interventions

pitavastatin DRUG

Also known as: Livalo

Pitavastatin

PLACEBO OTHER

Placebo

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men age 40-65yo
• BMI ≥ 27kg/m2 and waist circumference ≥102cm, high probability risk factors for NAFLD
• 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.
• 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
• No use of any statin within 1 year of study entry and not being actively considered for statin therapy by a treating provider.

You may not qualify if:

• Diagnosis of diabetes or use of anti-diabetic medications.
• Use of erythromycin, rifampin, cyclosporin, colchicine, or gemfibrozil.
• 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.
• Contraindication to statin therapy.
• Creatinine \> upper limit of normal or known renal disease
• AST or ALT \> 3 times the upper limit of normal
• hemoglobin \< 10g/dL
• Contraindication to undergoing a magnetic resonance scan.
• Atherosclerotic cardiovascular disease or low-density lipoprotein cholesterol (LDL-C) ≥ 190mg/dL.
• Triglyceride ≥500mg/dL

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (1)

• 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.

  PMID: 30239757 DERIVED

MeSH Terms

Conditions

Obesity; Non-alcoholic Fatty Liver Disease; Insulin Resistance; Fatty Liver

Interventions

pitavastatin

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Liver Diseases; Digestive System Diseases; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases

Results Point of Contact

• Title: Takara Stanley, MD
• Organization: Massachusetts General Hospital

tstanley@mgh.harvard.edu

6177249109

Study Officials

• Steven K Grinspoon, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

• Takara L Stanley, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Pediatrics

Study Record Dates

• First Submitted: November 8, 2014
• First Posted: November 13, 2014
• Study Start: March 2, 2015
• Primary Completion: April 30, 2018
• Study Completion: April 30, 2018
• Last Updated: July 2, 2019
• Results First Posted: July 2, 2019

Record last verified: 2019-06

Locations

US (1)