Trial Outcomes & Findings for Effects of Pitavastatin on Insulin Sensitivity and Liver Fat (NCT NCT02290106)

NCT ID: NCT02290106

Last Updated: 2019-07-02

Results Overview

insulin-stimulated glucose uptake measured by euglycemic hyperinsulinemic clamp

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 50 participants
• Primary outcome timeframe: 6 months
• Results posted on: 2019-07-02

Participant Flow

Participant milestones

Measure	Pitavastatin pitavastatin 4mg daily by mouth for 6 months pitavastatin	Placebo Identical placebo 4mg by mouth daily for 6 months PLACEBO
Overall Study STARTED	25	25
Overall Study COMPLETED	24	23
Overall Study NOT COMPLETED	1	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Only participants with baseline and final data were used in the calculation of baseline timepoints.

Baseline characteristics by cohort

Measure	Pitavastatin n=25 Participants pitavastatin 4mg daily by mouth for 6 months pitavastatin	Placebo n=25 Participants Identical placebo 4mg by mouth daily for 6 months PLACEBO	Total n=50 Participants Total of all reporting groups
Age, Continuous	52.8 years STANDARD_DEVIATION 6.5 • n=25 Participants	52.9 years STANDARD_DEVIATION 7 • n=25 Participants	52.8 years STANDARD_DEVIATION 6.7 • n=50 Participants
Sex: Female, Male Female	0 Participants n=25 Participants	0 Participants n=25 Participants	0 Participants n=50 Participants
Sex: Female, Male Male	25 Participants n=25 Participants	25 Participants n=25 Participants	50 Participants n=50 Participants
Race/Ethnicity, Customized White	24 Participants n=25 Participants	21 Participants n=25 Participants	45 Participants n=50 Participants
Race/Ethnicity, Customized Non-white	1 Participants n=25 Participants	3 Participants n=25 Participants	4 Participants n=50 Participants
Race/Ethnicity, Customized Not Reported	0 Participants n=25 Participants	1 Participants n=25 Participants	1 Participants n=50 Participants
Region of Enrollment United States	25 participants n=25 Participants	25 participants n=25 Participants	50 participants n=50 Participants
Low density lipoprotein cholesterol (LDL-C, mg/dL)	116 mg/dL STANDARD_DEVIATION 18 • n=24 Participants • Only participants with baseline and final data were used in the calculation of baseline timepoints.	125 mg/dL STANDARD_DEVIATION 22 • n=23 Participants • Only participants with baseline and final data were used in the calculation of baseline timepoints.	120 mg/dL STANDARD_DEVIATION 20 • n=47 Participants • Only participants with baseline and final data were used in the calculation of baseline timepoints.
Fasting glucose (mg/dL)	98 mg/dL STANDARD_DEVIATION 9 • n=24 Participants • Only participants with baseline and final data were used in the calculation of baseline timepoints.	97 mg/dL STANDARD_DEVIATION 9 • n=23 Participants • Only participants with baseline and final data were used in the calculation of baseline timepoints.	97 mg/dL STANDARD_DEVIATION 9 • n=47 Participants • Only participants with baseline and final data were used in the calculation of baseline timepoints.
Homeostasis model of insulin resistance (HOMA-IR)	2.1 HOMA-IR Score STANDARD_DEVIATION 1.9 • n=24 Participants • Only participants with baseline and final data were used in the calculation of baseline timepoints.	1.6 HOMA-IR Score STANDARD_DEVIATION 1.0 • n=23 Participants • Only participants with baseline and final data were used in the calculation of baseline timepoints.	1.8 HOMA-IR Score STANDARD_DEVIATION 1.5 • n=47 Participants • Only participants with baseline and final data were used in the calculation of baseline timepoints.
Liver fat content (hepatic fat fraction, %)	17 % STANDARD_DEVIATION 11 • n=23 Participants • Only participants with baseline and final data were used in the calculation of baseline timepoints. Five additional participants (1 pitavastatin \& 4 placebo) were unable to complete MRI due to inability to fit in the scanner or unanticipated claustrophobia, and 1 scan had unusable data due to technical error.	14 % STANDARD_DEVIATION 11 • n=18 Participants • Only participants with baseline and final data were used in the calculation of baseline timepoints. Five additional participants (1 pitavastatin \& 4 placebo) were unable to complete MRI due to inability to fit in the scanner or unanticipated claustrophobia, and 1 scan had unusable data due to technical error.	16 % STANDARD_DEVIATION 11 • n=41 Participants • Only participants with baseline and final data were used in the calculation of baseline timepoints. Five additional participants (1 pitavastatin \& 4 placebo) were unable to complete MRI due to inability to fit in the scanner or unanticipated claustrophobia, and 1 scan had unusable data due to technical error.

PRIMARY outcome

Timeframe: 6 months

Population: All patients with results for baseline and final. In addition to 3 participants who did not finish the study, 2 participants were unable to undergo clamp.

insulin-stimulated glucose uptake measured by euglycemic hyperinsulinemic clamp

Outcome measures

Measure	Pitavastatin n=22 Participants pitavastatin 4mg daily by mouth for 6 months pitavastatin	Placebo n=23 Participants Identical placebo 4mg by mouth daily for 6 months PLACEBO
Insulin-stimulated Glucose Uptake	5.9 mg/kg/minute Standard Deviation 2.1	5.9 mg/kg/minute Standard Deviation 1.6

PRIMARY outcome

Timeframe: 6 months

Population: All participants with baseline and final data were analyzed. In addition to patients who discontinued from the study, some patients were unable to have MRI scan due to inability to fit in the scanner or unanticipated claustrophobia.

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

Outcome measures

Measure	Pitavastatin n=21 Participants pitavastatin 4mg daily by mouth for 6 months pitavastatin	Placebo n=18 Participants Identical placebo 4mg by mouth daily for 6 months PLACEBO
Liver Fat	17 % liver fat (hepatic fat fraction) Standard Deviation 11	14 % liver fat (hepatic fat fraction) Standard Deviation 10

SECONDARY outcome

Timeframe: 6 months

Population: all patients with available data at baseline and final

alanine aminotransferase at the 6 month timepoint

Outcome measures

Measure	Pitavastatin n=24 Participants pitavastatin 4mg daily by mouth for 6 months pitavastatin	Placebo n=23 Participants Identical placebo 4mg by mouth daily for 6 months PLACEBO
Alanine Aminotransferase (ALT)	37 U/L Standard Deviation 38	27 U/L Standard Deviation 17

SECONDARY outcome

Timeframe: 6 months

Population: all patients with available data at baseline and final

aspartate aminotransferase at 6 month timepoint

Outcome measures

Measure	Pitavastatin n=24 Participants pitavastatin 4mg daily by mouth for 6 months pitavastatin	Placebo n=23 Participants Identical placebo 4mg by mouth daily for 6 months PLACEBO
Aspartate Aminotransferase (AST)	31 U/L Standard Deviation 23	26 U/L Standard Deviation 12

SECONDARY outcome

Timeframe: 6 months

Population: all patients with available data at baseline and final (note, in addition to 3 patients who discontinued, some patients were unable to undergo clamp procedure)

hepatic insulin sensitivity assessed by glucose infusion rate corrected for fluctuations in serum glucose ("M") during low-dose insulin clamp

Outcome measures

Measure	Pitavastatin n=20 Participants pitavastatin 4mg daily by mouth for 6 months pitavastatin	Placebo n=22 Participants Identical placebo 4mg by mouth daily for 6 months PLACEBO
Hepatic Insulin Sensitivity	1.5 mg/kg/minute Standard Deviation 1.0	1.6 mg/kg/minute Standard Deviation 0.7

SECONDARY outcome

Timeframe: 6 months

Outcome measures

Measure	Pitavastatin n=24 Participants pitavastatin 4mg daily by mouth for 6 months pitavastatin	Placebo n=23 Participants Identical placebo 4mg by mouth daily for 6 months PLACEBO
Hemoglobin A1c (HbA1c)	5.7 % (hemoglobin A1c) Standard Deviation 0.5	5.7 % (hemoglobin A1c) Standard Deviation 0.3

SECONDARY outcome

Timeframe: 6 months

quantitative insulin sensitivity check index (QUICKI) at 6 months. Measure = 1/((log(glucose in mg/dL) + log(insulin in uU/mL))

Outcome measures

Measure	Pitavastatin n=21 Participants pitavastatin 4mg daily by mouth for 6 months pitavastatin	Placebo n=23 Participants Identical placebo 4mg by mouth daily for 6 months PLACEBO
Quantitative Insulin Sensitivity Check Index (QUICKI)	0.16 QUICKI index Standard Deviation 0.02	0.15 QUICKI index Standard Deviation 0.02

Adverse Events

Pitavastatin

Serious events: 2 serious events

Other events: 16 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Measure	Pitavastatin n=25 participants at risk pitavastatin 4mg daily by mouth for 6 months pitavastatin	Placebo n=25 participants at risk Identical placebo 4mg by mouth daily for 6 months PLACEBO
General disorders Chest Pain	4.0% 1/25 • Number of events 1 • 6 months (during study period) Patients were asked at every study visit to recall any adverse events. (Patients were not contacted following study completion.)	0.00% 0/25 • 6 months (during study period) Patients were asked at every study visit to recall any adverse events. (Patients were not contacted following study completion.)
Gastrointestinal disorders Pancreatic Cancer	4.0% 1/25 • Number of events 1 • 6 months (during study period) Patients were asked at every study visit to recall any adverse events. (Patients were not contacted following study completion.)	0.00% 0/25 • 6 months (during study period) Patients were asked at every study visit to recall any adverse events. (Patients were not contacted following study completion.)
Gastrointestinal disorders Acute appendicitis	0.00% 0/25 • 6 months (during study period) Patients were asked at every study visit to recall any adverse events. (Patients were not contacted following study completion.)	4.0% 1/25 • Number of events 1 • 6 months (during study period) Patients were asked at every study visit to recall any adverse events. (Patients were not contacted following study completion.)

Other adverse events

Measure	Pitavastatin n=25 participants at risk pitavastatin 4mg daily by mouth for 6 months pitavastatin	Placebo n=25 participants at risk Identical placebo 4mg by mouth daily for 6 months PLACEBO
Gastrointestinal disorders Diarrhea or Loose Stools	12.0% 3/25 • 6 months (during study period) Patients were asked at every study visit to recall any adverse events. (Patients were not contacted following study completion.)	28.0% 7/25 • 6 months (during study period) Patients were asked at every study visit to recall any adverse events. (Patients were not contacted following study completion.)
Gastrointestinal disorders Any Gastrointestinal Symptoms	20.0% 5/25 • 6 months (during study period) Patients were asked at every study visit to recall any adverse events. (Patients were not contacted following study completion.)	32.0% 8/25 • 6 months (during study period) Patients were asked at every study visit to recall any adverse events. (Patients were not contacted following study completion.)
Musculoskeletal and connective tissue disorders Any Musculoskeletal Symptoms	16.0% 4/25 • 6 months (during study period) Patients were asked at every study visit to recall any adverse events. (Patients were not contacted following study completion.)	24.0% 6/25 • 6 months (during study period) Patients were asked at every study visit to recall any adverse events. (Patients were not contacted following study completion.)
Musculoskeletal and connective tissue disorders Muscle Cramps	16.0% 4/25 • 6 months (during study period) Patients were asked at every study visit to recall any adverse events. (Patients were not contacted following study completion.)	16.0% 4/25 • 6 months (during study period) Patients were asked at every study visit to recall any adverse events. (Patients were not contacted following study completion.)
General disorders Fatigue	8.0% 2/25 • 6 months (during study period) Patients were asked at every study visit to recall any adverse events. (Patients were not contacted following study completion.)	20.0% 5/25 • 6 months (during study period) Patients were asked at every study visit to recall any adverse events. (Patients were not contacted following study completion.)
Nervous system disorders Headache	0.00% 0/25 • 6 months (during study period) Patients were asked at every study visit to recall any adverse events. (Patients were not contacted following study completion.)	8.0% 2/25 • 6 months (during study period) Patients were asked at every study visit to recall any adverse events. (Patients were not contacted following study completion.)

Additional Information

Takara Stanley, MD

Massachusetts General Hospital

Phone: 6177249109

Email: tstanley@mgh.harvard.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place