Effects of Pitavastatin on Insulin Sensitivity and Liver Fat

• ClinicalTrials.gov Identifier: NCT02290106
• Recruitment Status: Completed
• First Posted: November 13, 2014
• Results First Posted: July 2, 2019
• Last Update Posted: July 2, 2019
• Sponsor: Massachusetts General Hospital
• Information provided by (Responsible Party): Takara Stanley, Massachusetts General Hospital

Tracking Information

• First Submitted Date: November 8, 2014
• First Posted Date: November 13, 2014
• Results First Submitted Date: March 22, 2019
• Results First Posted Date: July 2, 2019
• Last Update Posted Date: July 2, 2019
• Actual Study Start Date: March 2, 2015
• Actual Primary Completion Date: April 30, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 8, 2014)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 12, 2019)

• Alanine Aminotransferase (ALT) [ Time Frame: 6 months ]
  alanine aminotransferase at the 6 month timepoint
• Aspartate Aminotransferase (AST) [ Time Frame: 6 months ]
  aspartate aminotransferase at 6 month timepoint
• 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
• Hemoglobin A1c (HbA1c) [ Time Frame: 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))

Original Secondary Outcome Measures (submitted: November 8, 2014)

• Alanine Aminotransferase (ALT) [ Time Frame: 6 months ]
• Aspartate Aminotransferase (AST) [ Time Frame: 6 months ]
• Hepatic Insulin Sensitivity [ Time Frame: 6 months ]
  hepatic insulin sensitivity assessed by insulin suppression of hepatic gluconeogenesis during low-dose euglycemic hyperinsulinemic clamp
• Hemoglobin A1c (HbA1c) [ Time Frame: 6 months ]
• Quantitative Insulin Sensitivity Check Index (QUICKI) [ Time Frame: 6 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Effects of Pitavastatin on Insulin Sensitivity and Liver Fat
• Official Title: Effects of Pitavastatin on Insulin Sensitivity and Liver Fat
• 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 Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Obesity
• Fatty Liver, Nonalcoholic

Intervention

• Drug: pitavastatin
  Other Name: Livalo
• Other: PLACEBO

Study Arms

• Experimental: Pitavastatin
  pitavastatin 4mg daily by mouth for 6 months
  Intervention: Drug: pitavastatin
• Placebo Comparator: Placebo
  Identical placebo 4mg by mouth daily for 6 months
  Intervention: Other: PLACEBO

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 8, 2014): 50
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: April 30, 2018
• Actual Primary Completion Date: April 30, 2018 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 40 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02290106
• Other Study ID Numbers: 2014p-002117
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Takara Stanley, Massachusetts General Hospital
• Study Sponsor: Massachusetts General Hospital
• Collaborators: Not Provided

Investigators

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

• PRS Account: Massachusetts General Hospital
• Verification Date: June 2019