Trial Outcomes & Findings for A Trial of Lipitor (Atorvastatin) for the Treatment of Polycystic Ovary Syndrome (PCOS) in Women With Elevated Low-density Lipoprotein (LDL) Cholesterol (NCT NCT00529542)

NCT ID: NCT00529542

Last Updated: 2014-09-25

Results Overview

Brachial artery FMD, the percent change in brachial artery diameter following release of transient occlusion, was selected as the primary outcome because it is the most widely used research tool for evaluating the effects of interventions on endothelial function. FMD has been shown to predict longterm cardiovascular events, even in patients with no apparent heart disease.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 20 participants
• Primary outcome timeframe: baseline and 6 weeks
• Results posted on: 2014-09-25

Participant Flow

Participants were recruited through the clinics of the Departments of Medicine and Obstetrics and Gynecology at Penn State Hershey Medical Center from October 20, 2006 to September 8, 2008.

Participant milestones

Measure	Atorvastatin Atorvastatin, 40 mg qd	Placebo Placebo qd
Overall Study STARTED	9	11
Overall Study COMPLETED	8	10
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Measure	Atorvastatin Atorvastatin, 40 mg qd	Placebo Placebo qd
Overall Study Withdrawal by Subject	1	0
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

A Trial of Lipitor (Atorvastatin) for the Treatment of Polycystic Ovary Syndrome (PCOS) in Women With Elevated Low-density Lipoprotein (LDL) Cholesterol

Baseline characteristics by cohort

Measure	Atorvastatin n=9 Participants Atorvastatin, 40 mg qd	Placebo n=11 Participants Placebo qd	Total n=20 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	9 Participants n=5 Participants	11 Participants n=7 Participants	20 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	11 Participants n=7 Participants	20 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	9 participants n=5 Participants	11 participants n=7 Participants	20 participants n=5 Participants

PRIMARY outcome

Timeframe: baseline and 6 weeks

Population: All analyses were performed by intention-to-treat.

Brachial artery FMD, the percent change in brachial artery diameter following release of transient occlusion, was selected as the primary outcome because it is the most widely used research tool for evaluating the effects of interventions on endothelial function. FMD has been shown to predict longterm cardiovascular events, even in patients with no apparent heart disease.

Outcome measures

Measure	Atorvastatin n=9 Participants Atorvastatin, 40 mg qd	Placebo n=11 Participants Placebo qd
Brachial Artery Flow-mediated Dilation (FMD) Before treatment	12.0 % change in brachial artery diameter Standard Deviation 7.3	9.8 % change in brachial artery diameter Standard Deviation 5.8
Brachial Artery Flow-mediated Dilation (FMD) After treatment	10.4 % change in brachial artery diameter Standard Deviation 4.6	10.2 % change in brachial artery diameter Standard Deviation 2.9

SECONDARY outcome

Timeframe: baseline and 6 weeks

Population: All analyses were performed by intention-to-treat.

Pneumatic cuffs were positioned on the upper arm and wrist of the experimental arm. The brachial artery was imaged using an ATL Doppler ultrasound probe (5-12MHz linear array scanhead, HDI 5000, Advanced Technology Laboratories, Bothell, WA). Mean blood flow velocity (MBV) and brachial artery diameter (BAD) were recorded at baseline. Then the wrist cuff was inflated to 200-250 mmHg. After a minute, with the wrist cuff still inflated, the arm cuff was inflated to 200-250 mmHg. After 10 minutes the arm cuff was released to induce reactive hyperemia in the brachial artery. Upon release of the arm cuff, we continuously measured blood pressure (BP), heart rate (HR), and MBV, and intermittently measured BAD in the experimental arm. Brachial artery conductance (BAC)was calculated as MBV/MAP and FMD was calculated as percent change in BAD from baseline.

Outcome measures

Measure	Atorvastatin n=9 Participants Atorvastatin, 40 mg qd	Placebo n=11 Participants Placebo qd
Peak Brachial Artery Conductance (BAC) After treatment	6.9 ml/sec/mm Hg Standard Deviation 2.8	4.3 ml/sec/mm Hg Standard Deviation 3.3
Peak Brachial Artery Conductance (BAC) Before treatment	5.4 ml/sec/mm Hg Standard Deviation 2.9	3.6 ml/sec/mm Hg Standard Deviation 3.0

SECONDARY outcome

Timeframe: baseline and 6 weeks

Population: All analyses were performed by intention-to-treat.

Outcome measures

Measure	Atorvastatin n=9 Participants Atorvastatin, 40 mg qd	Placebo n=11 Participants Placebo qd
Total Cholesterol Before treatment	215.8 mg/dl Standard Deviation 39.0	202.8 mg/dl Standard Deviation 28.3
Total Cholesterol After treatment	132.0 mg/dl Standard Deviation 19.7	192.1 mg/dl Standard Deviation 33.6

SECONDARY outcome

Timeframe: baseline and 6 weeks

Population: All analyses were performed by intention-to-treat.

Outcome measures

Measure	Atorvastatin n=9 Participants Atorvastatin, 40 mg qd	Placebo n=11 Participants Placebo qd
LDL Cholesterol Before treatment	140.7 mg/dl Standard Deviation 24.6	131.3 mg/dl Standard Deviation 21.6
LDL Cholesterol After treatment	68.5 mg/dl Standard Deviation 19.3	118.8 mg/dl Standard Deviation 26.8

SECONDARY outcome

Timeframe: baseline and 6 weeks

Population: All analyses were performed by intention-to-treat.

Outcome measures

Measure	Atorvastatin n=9 Participants Atorvastatin, 40 mg qd	Placebo n=11 Participants Placebo qd
HDL Cholesterol Before treatment	44.4 mg/dl Standard Deviation 14.6	46.5 mg/dl Standard Deviation 8.6
HDL Cholesterol After treatment	47.8 mg/dl Standard Deviation 11.8	46.8 mg/dl Standard Deviation 8.4

SECONDARY outcome

Timeframe: baseline and 6 weeks

Population: All analyses were performed by intention-to-treat.

Outcome measures

Measure	Atorvastatin n=9 Participants Atorvastatin, 40 mg qd	Placebo n=11 Participants Placebo qd
Triglycerides Before treatment	153.3 mg/dl Standard Deviation 84.9	125.5 mg/dl Standard Deviation 54.2
Triglycerides After treatment	78.5 mg/dl Standard Deviation 24.8	132.5 mg/dl Standard Deviation 45.7

SECONDARY outcome

Timeframe: baseline and 6 weeks

Population: All analyses were performed by intention-to-treat.

Outcome measures

Measure	Atorvastatin n=9 Participants Atorvastatin, 40 mg qd	Placebo n=11 Participants Placebo qd
Fasting Glucose Before treatment	87.7 mg/dl Standard Deviation 9.0	85.3 mg/dl Standard Deviation 8.0
Fasting Glucose After treatment	87.8 mg/dl Standard Deviation 8.5	88.9 mg/dl Standard Deviation 10.7

SECONDARY outcome

Timeframe: baseline and 6 weeks

Population: All analyses were performed by intention-to-treat.

Outcome measures

Measure	Atorvastatin n=9 Participants Atorvastatin, 40 mg qd	Placebo n=11 Participants Placebo qd
Fasting Insulin Before treatment	18.6 uU/ml Standard Deviation 10.1	16.8 uU/ml Standard Deviation 9.5
Fasting Insulin After treatment	21.0 uU/ml Standard Deviation 11.8	15.9 uU/ml Standard Deviation 6.7

SECONDARY outcome

Timeframe: baseline and 6 weeks

Population: All analyses were performed by intention-to-treat.

A 75 gram oral glucose tolerance test (OGTT) was performed with blood draws at 0, 30, 60, 90 and 120 minutes.

Outcome measures

Measure	Atorvastatin n=9 Participants Atorvastatin, 40 mg qd	Placebo n=11 Participants Placebo qd
Area Under the Curve (AUC) for Glucose During OGTT Before treatment	15693 mg*minute/dL Standard Deviation 2162	15309 mg*minute/dL Standard Deviation 3692
Area Under the Curve (AUC) for Glucose During OGTT After treatment	16136 mg*minute/dL Standard Deviation 2569	15448 mg*minute/dL Standard Deviation 3165

SECONDARY outcome

Timeframe: baseline and 6 weeks

Population: All analyses were performed by intention-to-treat.

Area under the curve for insulin during OGTT: A 75 gram oral glucose tolerance test was performed with blood draws at 0, 30, 60, 90 and 120 minutes.

Outcome measures

Measure	Atorvastatin n=9 Participants Atorvastatin, 40 mg qd	Placebo n=11 Participants Placebo qd
AUC for Insulin Before treatment	12738 uU*minute/mL Standard Deviation 10010	9338 uU*minute/mL Standard Deviation 5208
AUC for Insulin After treatment	17479 uU*minute/mL Standard Deviation 11929	9132 uU*minute/mL Standard Deviation 4466

SECONDARY outcome

Timeframe: baseline and 6 weeks

Population: All analyses were performed by intention-to-treat.

Outcome measures

Measure	Atorvastatin n=9 Participants Atorvastatin, 40 mg qd	Placebo n=11 Participants Placebo qd
Total Testosterone Before treatment	61.3 ng/dl Standard Deviation 16.9	92.3 ng/dl Standard Deviation 49.8
Total Testosterone After treatment	47.1 ng/dl Standard Deviation 21.4	75.7 ng/dl Standard Deviation 43.6

SECONDARY outcome

Timeframe: baseline and 6 weeks

Population: All analyses were performed by intention-to-treat.

Outcome measures

Measure	Atorvastatin n=9 Participants Atorvastatin, 40 mg qd	Placebo n=11 Participants Placebo qd
Androstenedione Before treatment	3.4 ng/ml Standard Deviation 0.8	3.8 ng/ml Standard Deviation 1.2
Androstenedione After treatment	2.5 ng/ml Standard Deviation 0.9	4.1 ng/ml Standard Deviation 1.2

SECONDARY outcome

Timeframe: baseline and 6 weeks

Population: All analyses were performed by intention-to-treat.

Dehydroepiandrosterone sulfate

Outcome measures

Measure	Atorvastatin n=9 Participants Atorvastatin, 40 mg qd	Placebo n=11 Participants Placebo qd
DHEAS Before treatment	1630.0 ng/ml Standard Deviation 873.1	1701.5 ng/ml Standard Deviation 681.3
DHEAS After treatment	1326.4 ng/ml Standard Deviation 854.3	1739.5 ng/ml Standard Deviation 781.8

OTHER_PRE_SPECIFIED outcome

Timeframe: baseline and 6 weeks

Population: All analyses were performed by intention-to-treat.

high sensitive C-reactive protein as a measure of inflammation

Outcome measures

Measure	Atorvastatin n=9 Participants Atorvastatin, 40 mg qd	Placebo n=11 Participants Placebo qd
High-sensitivity C-reactive Protein (hsCRP) Before treatment	8.0 mg/L Standard Deviation 9.6	7.2 mg/L Standard Deviation 7.7
High-sensitivity C-reactive Protein (hsCRP) After treatment	4.3 mg/L Standard Deviation 5.4	6.0 mg/L Standard Deviation 7.3

POST_HOC outcome

Timeframe: baseline and 6 weeks

Population: All analyses were performed by intention-to-treat.

Outcome measures

Measure	Atorvastatin n=9 Participants Atorvastatin, 40 mg qd	Placebo n=11 Participants Placebo qd
Systolic Blood Pressure Before treatment	119.8 mm Hg Standard Deviation 15.8	114.5 mm Hg Standard Deviation 14.4
Systolic Blood Pressure After treatment	112.0 mm Hg Standard Deviation 13.2	111.4 mm Hg Standard Deviation 8.8

POST_HOC outcome

Timeframe: baseline and 6 weeks

Population: All analyses were performed by intention-to-treat.

Outcome measures

Measure	Atorvastatin n=9 Participants Atorvastatin, 40 mg qd	Placebo n=11 Participants Placebo qd
Diastolic Blood Pressure Before treatment	70.8 mm Hg Standard Deviation 14.8	64.6 mm Hg Standard Deviation 8.0
Diastolic Blood Pressure After treatment	64.3 mm Hg Standard Deviation 12.3	65.4 mm Hg Standard Deviation 8.1

POST_HOC outcome

Timeframe: baseline and 6 weeks

Population: All analyses were performed by intention-to-treat.

Pelvic ultrasound was performed using the 6.5 megahertz (MHz) probe of an ATL 400 machine to characterize ovarian size and morphology. Since in vitro studies demonstrate that statins inhibit ovarian theca-interstitial cell proliferation, we hypothesized that statins might reduce ovarian volume in PCOS.

Outcome measures

Measure	Atorvastatin n=9 Participants Atorvastatin, 40 mg qd	Placebo n=11 Participants Placebo qd
Mean Ovarian Volume Before treatment	15.1 mm3 Standard Deviation 8.8	25.4 mm3 Standard Deviation 13.7
Mean Ovarian Volume After treatment	19.2 mm3 Standard Deviation 7.0	25.2 mm3 Standard Deviation 9.9

POST_HOC outcome

Timeframe: baseline and 6 weeks

Population: All analyses were performed by intention-to-treat.

Outcome measures

Measure	Atorvastatin n=9 Participants Atorvastatin, 40 mg qd	Placebo n=11 Participants Placebo qd
Body Mass Index Before treatment	40.1 kg/m2 Standard Deviation 11.8	36.0 kg/m2 Standard Deviation 10.4
Body Mass Index After treatment	38.2 kg/m2 Standard Deviation 8.4	35.8 kg/m2 Standard Deviation 10.8

Adverse Events

Atorvastatin

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Measure	Atorvastatin n=9 participants at risk Atorvastatin, 40 mg qd	Placebo n=11 participants at risk Placebo qd
Hepatobiliary disorders gallbladder removal	11.1% 1/9 • Number of events 1 • 6 weeks	0.00% 0/11 • 6 weeks

Other adverse events

Measure	Atorvastatin n=9 participants at risk Atorvastatin, 40 mg qd	Placebo n=11 participants at risk Placebo qd
General disorders swelling	0.00% 0/9 • 6 weeks	9.1% 1/11 • Number of events 1 • 6 weeks
Musculoskeletal and connective tissue disorders muscle pain	11.1% 1/9 • Number of events 1 • 6 weeks	0.00% 0/11 • 6 weeks
Nervous system disorders headache	0.00% 0/9 • 6 weeks	9.1% 1/11 • Number of events 1 • 6 weeks

Additional Information

Richard S. Legro

Milton S. Hershey Medical Center

Phone: 717-531-8478

Email: rsl1@psu.edu

Results disclosure agreements

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