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Effects of Pitavastatin on Insulin Sensitivity and Liver Fat

Primary Purpose

Obesity, Fatty Liver, Nonalcoholic

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
pitavastatin
PLACEBO
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Obesity focused on measuring obesity, insulin sensitivity, statin (HMG-CoA Reductase Inhibitor), fatty liver

Eligibility Criteria

40 Years - 65 Years (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

  • Massachusetts General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Pitavastatin

Placebo

Arm Description

pitavastatin 4mg daily by mouth for 6 months

Identical placebo 4mg by mouth daily for 6 months

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
November 8, 2014
Last Updated
June 12, 2019
Sponsor
Massachusetts General Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT02290106
Brief Title
Effects of Pitavastatin on Insulin Sensitivity and Liver Fat
Official Title
Effects of Pitavastatin on Insulin Sensitivity and Liver Fat
Study Type
Interventional

2. Study Status

Record Verification Date
June 2019
Overall Recruitment Status
Completed
Study Start Date
March 2, 2015 (Actual)
Primary Completion Date
April 30, 2018 (Actual)
Study Completion Date
April 30, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obesity, Fatty Liver, Nonalcoholic
Keywords
obesity, insulin sensitivity, statin (HMG-CoA Reductase Inhibitor), fatty liver

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Pitavastatin
Arm Type
Experimental
Arm Description
pitavastatin 4mg daily by mouth for 6 months
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Identical placebo 4mg by mouth daily for 6 months
Intervention Type
Drug
Intervention Name(s)
pitavastatin
Other Intervention Name(s)
Livalo
Intervention Type
Other
Intervention Name(s)
PLACEBO
Primary Outcome Measure Information:
Title
Insulin-stimulated Glucose Uptake
Description
insulin-stimulated glucose uptake measured by euglycemic hyperinsulinemic clamp
Time Frame
6 months
Title
Liver Fat
Description
liver fat content as measured by 1H-magnetic resonance spectroscopy
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Alanine Aminotransferase (ALT)
Description
alanine aminotransferase at the 6 month timepoint
Time Frame
6 months
Title
Aspartate Aminotransferase (AST)
Description
aspartate aminotransferase at 6 month timepoint
Time Frame
6 months
Title
Hepatic Insulin Sensitivity
Description
hepatic insulin sensitivity assessed by glucose infusion rate corrected for fluctuations in serum glucose ("M") during low-dose insulin clamp
Time Frame
6 months
Title
Hemoglobin A1c (HbA1c)
Time Frame
6 months
Title
Quantitative Insulin Sensitivity Check Index (QUICKI)
Description
quantitative insulin sensitivity check index (QUICKI) at 6 months. Measure = 1/((log(glucose in mg/dL) + log(insulin in uU/mL))
Time Frame
6 months

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. 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 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: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven K Grinspoon, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Takara L Stanley, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
30239757
Citation
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.
Results Reference
derived

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Effects of Pitavastatin on Insulin Sensitivity and Liver Fat

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