Trial Outcomes & Findings for Treatment of Hyperandrogenism Versus Insulin Resistance in Infertile Polycystic Ovary Syndrome (PCOS) Women (NCT NCT00704912)
NCT ID: NCT00704912
Last Updated: 2016-11-07
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
217 participants
Primary outcome timeframe
Participants were followed for 4 months of attempted conception and those who conceived were then followed for the duration of their pregnancy, approximately 9 months.
Results posted on
2016-11-07
Participant Flow
217 subjects consented for the study, of which 149 were randomized to one of the 3 treatment groups. Sixty-eight subjects were not randomized because they withdrew prior to randomization or were determined ineligible during the screening process.
Participant milestones
| Measure |
Lifestyle Intervention
Orlistat/Meal Replacement/Lifestyle Modification: Orlistat will be given at 60 mg three times per day (1 tablet 3 times a day) before meals, i.e., breakfast, lunch, and dinner.
|
Oral Contraceptives (OCP)
Loestrin 1/20: Patients will be started on a low dose containing OCP (20 mcg ethinyl estradiol/1 mg norethindrone acetate daily) for a continuous 4 month period.
|
Lifestyle/OCP Combined
Combination of treatments: Medications will be administered as described for the other 2 arms.
|
|---|---|---|---|
|
Overall Study
STARTED
|
50
|
49
|
50
|
|
Overall Study
COMPLETED
|
44
|
45
|
43
|
|
Overall Study
NOT COMPLETED
|
6
|
4
|
7
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Treatment of Hyperandrogenism Versus Insulin Resistance in Infertile Polycystic Ovary Syndrome (PCOS) Women
Baseline characteristics by cohort
| Measure |
Lifestyle Intervention
n=50 Participants
Orlistat/Meal Replacement/Lifestyle Modification: Orlistat will be given at 60 mg three times per day (1 tablet 3 times a day) before meals, i.e., breakfast, lunch, and dinner.
|
Oral Contraceptives (OCP)
n=49 Participants
Loestrin 1/20: Patients will be started on a low dose containing OCP (20 mcg ethinyl estradiol/1 mg norethindrone acetate daily) for a continuous 4 month period.
|
Lifestyle/OCP Combined
n=50 Participants
Combination of treatments: Medications will be administered as described for the other 2 arms.
|
Total
n=149 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
28.6 years
STANDARD_DEVIATION 3.4 • n=5 Participants
|
29.8 years
STANDARD_DEVIATION 3.7 • n=7 Participants
|
28.7 years
STANDARD_DEVIATION 4.2 • n=5 Participants
|
29.0 years
STANDARD_DEVIATION 3.8 • n=4 Participants
|
|
Gender
Female
|
50 Participants
n=5 Participants
|
49 Participants
n=7 Participants
|
50 Participants
n=5 Participants
|
149 Participants
n=4 Participants
|
|
Gender
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
17 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
44 Participants
n=5 Participants
|
43 Participants
n=7 Participants
|
45 Participants
n=5 Participants
|
132 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
7 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
28 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
35 Participants
n=5 Participants
|
40 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
106 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
5 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
11 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Parity
0 births
|
41 participants
n=5 Participants
|
38 participants
n=7 Participants
|
45 participants
n=5 Participants
|
124 participants
n=4 Participants
|
|
Parity
>0 births
|
9 participants
n=5 Participants
|
11 participants
n=7 Participants
|
5 participants
n=5 Participants
|
25 participants
n=4 Participants
|
|
Weight
|
96.0 kg
STANDARD_DEVIATION 15.8 • n=5 Participants
|
94.6 kg
STANDARD_DEVIATION 14.4 • n=7 Participants
|
95.2 kg
STANDARD_DEVIATION 14.5 • n=5 Participants
|
95.3 kg
STANDARD_DEVIATION 14.8 • n=4 Participants
|
|
Body Mass Index (BMI)
|
35.1 kg/m2
STANDARD_DEVIATION 4.6 • n=5 Participants
|
35.1 kg/m2
STANDARD_DEVIATION 4.2 • n=7 Participants
|
35.5 kg/m2
STANDARD_DEVIATION 4.4 • n=5 Participants
|
35.2 kg/m2
STANDARD_DEVIATION 4.4 • n=4 Participants
|
|
Metabolic Syndrome
Yes
|
18 participants
n=5 Participants
|
14 participants
n=7 Participants
|
21 participants
n=5 Participants
|
53 participants
n=4 Participants
|
|
Metabolic Syndrome
No
|
31 participants
n=5 Participants
|
34 participants
n=7 Participants
|
29 participants
n=5 Participants
|
94 participants
n=4 Participants
|
|
Metabolic Syndrome
Unknown
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
0 participants
n=5 Participants
|
2 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Participants were followed for 4 months of attempted conception and those who conceived were then followed for the duration of their pregnancy, approximately 9 months.Outcome measures
| Measure |
Lifestyle Intervention
n=50 Participants
Orlistat/Meal Replacement/Lifestyle Modification: Orlistat will be given at 60 mg three times per day (1 tablet 3 times a day) before meals, i.e., breakfast, lunch, and dinner.
|
Oral Contraceptives (OCP)
n=49 Participants
Loestrin 1/20: Patients will be started on a low dose containing OCP (20 mcg ethinyl estradiol/1 mg norethindrone acetate daily) for a continuous 4 month period.
|
Lifestyle/OCP Combined
n=50 Participants
Combination of treatments: Medications will be administered as described for the other 2 arms.
|
|---|---|---|---|
|
Live Birth Rate
|
13 participants
|
5 participants
|
12 participants
|
SECONDARY outcome
Timeframe: Up to 4 monthsOutcome measures
| Measure |
Lifestyle Intervention
n=136 Clomiphene Treatment Cycles
Orlistat/Meal Replacement/Lifestyle Modification: Orlistat will be given at 60 mg three times per day (1 tablet 3 times a day) before meals, i.e., breakfast, lunch, and dinner.
|
Oral Contraceptives (OCP)
n=154 Clomiphene Treatment Cycles
Loestrin 1/20: Patients will be started on a low dose containing OCP (20 mcg ethinyl estradiol/1 mg norethindrone acetate daily) for a continuous 4 month period.
|
Lifestyle/OCP Combined
n=140 Clomiphene Treatment Cycles
Combination of treatments: Medications will be administered as described for the other 2 arms.
|
|---|---|---|---|
|
Ovulation Rate
|
82 total number of ovulations
|
71 total number of ovulations
|
94 total number of ovulations
|
SECONDARY outcome
Timeframe: Baseline, 4 monthsChange from baseline to end of the 4-month intervention.
Outcome measures
| Measure |
Lifestyle Intervention
n=50 Participants
Orlistat/Meal Replacement/Lifestyle Modification: Orlistat will be given at 60 mg three times per day (1 tablet 3 times a day) before meals, i.e., breakfast, lunch, and dinner.
|
Oral Contraceptives (OCP)
n=49 Participants
Loestrin 1/20: Patients will be started on a low dose containing OCP (20 mcg ethinyl estradiol/1 mg norethindrone acetate daily) for a continuous 4 month period.
|
Lifestyle/OCP Combined
n=50 Participants
Combination of treatments: Medications will be administered as described for the other 2 arms.
|
|---|---|---|---|
|
Change in Weight
|
-6.2 kg
Interval -7.1 to -5.3
|
-1.1 kg
Interval -2.0 to -0.3
|
-6.1 kg
Interval -7.0 to -5.2
|
SECONDARY outcome
Timeframe: Baseline, 4 monthsOutcome measures
| Measure |
Lifestyle Intervention
n=50 Participants
Orlistat/Meal Replacement/Lifestyle Modification: Orlistat will be given at 60 mg three times per day (1 tablet 3 times a day) before meals, i.e., breakfast, lunch, and dinner.
|
Oral Contraceptives (OCP)
n=49 Participants
Loestrin 1/20: Patients will be started on a low dose containing OCP (20 mcg ethinyl estradiol/1 mg norethindrone acetate daily) for a continuous 4 month period.
|
Lifestyle/OCP Combined
n=50 Participants
Combination of treatments: Medications will be administered as described for the other 2 arms.
|
|---|---|---|---|
|
Prevalence of Metabolic Syndrome
Metabolic Syndrome at Baseline
|
18 participants
|
14 participants
|
21 participants
|
|
Prevalence of Metabolic Syndrome
Metabolic Syndrome at End of Intervention
|
18 participants
|
21 participants
|
16 participants
|
Adverse Events
Lifestyle Intervention
Serious events: 3 serious events
Other events: 32 other events
Deaths: 0 deaths
Oral Contraceptives (OCP)
Serious events: 0 serious events
Other events: 37 other events
Deaths: 0 deaths
Lifestyle/OCP Combined
Serious events: 1 serious events
Other events: 43 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Lifestyle Intervention
n=50 participants at risk
Orlistat/Meal Replacement/Lifestyle Modification: Orlistat will be given at 60 mg three times per day (1 tablet 3 times a day) before meals, i.e., breakfast, lunch, and dinner.
|
Oral Contraceptives (OCP)
n=49 participants at risk
Loestrin 1/20: Patients will be started on a low dose containing OCP (20 mcg ethinyl estradiol/1 mg norethindrone acetate daily) for a continuous 4 month period.
|
Lifestyle/OCP Combined
n=50 participants at risk
Combination of treatments: Medications will be administered as described for the other 2 arms.
|
|---|---|---|---|
|
Reproductive system and breast disorders
Abnormal uterine bleeding
|
2.0%
1/50 • Number of events 1
|
0.00%
0/49
|
0.00%
0/50
|
|
Pregnancy, puerperium and perinatal conditions
Ectopic pregnancy
|
2.0%
1/50 • Number of events 1
|
0.00%
0/49
|
0.00%
0/50
|
|
Pregnancy, puerperium and perinatal conditions
Preterm delivery
|
2.0%
1/50 • Number of events 1
|
0.00%
0/49
|
0.00%
0/50
|
|
Gastrointestinal disorders
Perforated appendix
|
0.00%
0/50
|
0.00%
0/49
|
2.0%
1/50 • Number of events 1
|
Other adverse events
| Measure |
Lifestyle Intervention
n=50 participants at risk
Orlistat/Meal Replacement/Lifestyle Modification: Orlistat will be given at 60 mg three times per day (1 tablet 3 times a day) before meals, i.e., breakfast, lunch, and dinner.
|
Oral Contraceptives (OCP)
n=49 participants at risk
Loestrin 1/20: Patients will be started on a low dose containing OCP (20 mcg ethinyl estradiol/1 mg norethindrone acetate daily) for a continuous 4 month period.
|
Lifestyle/OCP Combined
n=50 participants at risk
Combination of treatments: Medications will be administered as described for the other 2 arms.
|
|---|---|---|---|
|
Gastrointestinal disorders
Steatorrhea/Diarrhea
|
12.0%
6/50
|
0.00%
0/49
|
24.0%
12/50
|
|
General disorders
Headache
|
9.1%
4/44
|
13.6%
6/44
|
27.9%
12/43
|
|
Respiratory, thoracic and mediastinal disorders
Upper Respiratory Infections
|
4.5%
2/44
|
11.4%
5/44
|
11.6%
5/43
|
|
General disorders
Nausea/Vomiting
|
11.4%
5/44
|
6.8%
3/44
|
11.6%
5/43
|
|
Reproductive system and breast disorders
Breast Pain
|
11.4%
5/44
|
15.9%
7/44
|
20.9%
9/43
|
|
General disorders
Abdominal Pain
|
4.5%
2/44
|
6.8%
3/44
|
2.3%
1/43
|
|
Reproductive system and breast disorders
Dysmenorrhea
|
2.3%
1/44
|
13.6%
6/44
|
2.3%
1/43
|
|
Gastrointestinal disorders
Constipation
|
4.5%
2/44
|
4.5%
2/44
|
7.0%
3/43
|
|
Reproductive system and breast disorders
Abnormal uterine bleeding
|
0.00%
0/50
|
8.2%
4/49
|
12.0%
6/50
|
|
Psychiatric disorders
Mood Swings
|
6.8%
3/44
|
6.8%
3/44
|
4.7%
2/43
|
|
Gastrointestinal disorders
Gas/Bloating
|
9.1%
4/44
|
2.3%
1/44
|
7.0%
3/43
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain
|
2.0%
1/50
|
6.1%
3/49
|
8.0%
4/50
|
|
Reproductive system and breast disorders
Vaginitis/Vulvitis
|
2.0%
1/50
|
8.2%
4/49
|
2.0%
1/50
|
|
Reproductive system and breast disorders
Pelvic Pain
|
15.9%
7/44
|
27.3%
12/44
|
30.2%
13/43
|
|
General disorders
Dry Mouth
|
8.0%
4/50
|
0.00%
0/49
|
2.0%
1/50
|
|
General disorders
Dizziness/Vertigo
|
6.0%
3/50
|
4.1%
2/49
|
0.00%
0/50
|
|
General disorders
Fatigue
|
4.5%
2/44
|
2.3%
1/44
|
7.0%
3/43
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
2.0%
1/50
|
2.0%
1/49
|
6.0%
3/50
|
|
Gastrointestinal disorders
Dyspepsia
|
4.0%
2/50
|
0.00%
0/49
|
6.0%
3/50
|
|
General disorders
Insomnia
|
4.0%
2/50
|
0.00%
0/49
|
6.0%
3/50
|
|
General disorders
Tachycardia
|
2.0%
1/50
|
0.00%
0/49
|
6.0%
3/50
|
|
Reproductive system and breast disorders
Hot flushes
|
9.1%
4/44
|
13.6%
6/44
|
7.0%
3/43
|
|
General disorders
Visual Changes
|
2.3%
1/44
|
0.00%
0/44
|
7.0%
3/43
|
|
Reproductive system and breast disorders
Vaginal Dryness/Pain
|
0.00%
0/44
|
6.8%
3/44
|
0.00%
0/43
|
|
Pregnancy, puerperium and perinatal conditions
Nausea/Vomiting
|
25.0%
4/16
|
0.00%
0/8
|
7.1%
1/14
|
|
Pregnancy, puerperium and perinatal conditions
Fatigue
|
18.8%
3/16
|
0.00%
0/8
|
7.1%
1/14
|
|
Pregnancy, puerperium and perinatal conditions
Pelvic Pain
|
18.8%
3/16
|
0.00%
0/8
|
7.1%
1/14
|
|
Pregnancy, puerperium and perinatal conditions
Breast Pain
|
6.2%
1/16
|
0.00%
0/8
|
14.3%
2/14
|
|
Pregnancy, puerperium and perinatal conditions
Headache
|
0.00%
0/16
|
0.00%
0/8
|
7.1%
1/14
|
|
Pregnancy, puerperium and perinatal conditions
Mood Swings
|
6.2%
1/16
|
0.00%
0/8
|
7.1%
1/14
|
|
Pregnancy, puerperium and perinatal conditions
Constipation
|
6.2%
1/16
|
0.00%
0/8
|
7.1%
1/14
|
|
Pregnancy, puerperium and perinatal conditions
Hot flushes
|
12.5%
2/16
|
0.00%
0/8
|
0.00%
0/14
|
|
Pregnancy, puerperium and perinatal conditions
Spotting in pregnancy
|
6.2%
1/16
|
0.00%
0/8
|
7.1%
1/14
|
|
Pregnancy, puerperium and perinatal conditions
Hypertension
|
6.2%
1/16
|
0.00%
0/8
|
0.00%
0/14
|
|
Pregnancy, puerperium and perinatal conditions
Vaginitis/Vulvitis
|
0.00%
0/16
|
0.00%
0/8
|
7.1%
1/14
|
|
Pregnancy, puerperium and perinatal conditions
Vaginal Dryness/Pain
|
6.2%
1/16
|
0.00%
0/8
|
0.00%
0/14
|
|
Pregnancy, puerperium and perinatal conditions
Hyperemesis
|
6.2%
1/16
|
0.00%
0/8
|
0.00%
0/14
|
|
Pregnancy, puerperium and perinatal conditions
Urinary tract infection in pregnancy
|
0.00%
0/16
|
0.00%
0/8
|
7.1%
1/14
|
|
Pregnancy, puerperium and perinatal conditions
Dizziness/Vertigo
|
0.00%
0/16
|
12.5%
1/8
|
0.00%
0/14
|
|
Pregnancy, puerperium and perinatal conditions
Rash
|
0.00%
0/16
|
12.5%
1/8
|
0.00%
0/14
|
|
Pregnancy, puerperium and perinatal conditions
Gas/Bloating
|
6.2%
1/16
|
0.00%
0/8
|
0.00%
0/14
|
|
Pregnancy, puerperium and perinatal conditions
Abdominal Pain
|
6.2%
1/16
|
0.00%
0/8
|
0.00%
0/14
|
|
Pregnancy, puerperium and perinatal conditions
Dyspepsia
|
0.00%
0/16
|
0.00%
0/8
|
7.1%
1/14
|
|
Pregnancy, puerperium and perinatal conditions
Pre-eclampsia
|
25.0%
4/16
|
12.5%
1/8
|
14.3%
2/14
|
|
Pregnancy, puerperium and perinatal conditions
Gestational Diabetes
|
18.8%
3/16
|
12.5%
1/8
|
14.3%
2/14
|
|
Pregnancy, puerperium and perinatal conditions
Preterm Delivery
|
18.8%
3/16
|
0.00%
0/8
|
0.00%
0/14
|
|
Pregnancy, puerperium and perinatal conditions
Premature Rupture of Membranes
|
18.8%
3/16
|
0.00%
0/8
|
0.00%
0/14
|
|
Pregnancy, puerperium and perinatal conditions
Upper Respiratory Infections
|
18.8%
3/16
|
0.00%
0/8
|
0.00%
0/14
|
|
Pregnancy, puerperium and perinatal conditions
Placental Abnormalities
|
6.2%
1/16
|
12.5%
1/8
|
0.00%
0/14
|
|
Pregnancy, puerperium and perinatal conditions
Dental abscess
|
6.2%
1/16
|
0.00%
0/8
|
0.00%
0/14
|
|
Pregnancy, puerperium and perinatal conditions
Dental, other
|
6.2%
1/16
|
0.00%
0/8
|
0.00%
0/14
|
|
Pregnancy, puerperium and perinatal conditions
Other specified disorders of biliary tract
|
0.00%
0/16
|
0.00%
0/8
|
7.1%
1/14
|
|
Pregnancy, puerperium and perinatal conditions
Breast lump
|
0.00%
0/16
|
0.00%
0/8
|
7.1%
1/14
|
|
Pregnancy, puerperium and perinatal conditions
Incompetent cervix
|
6.2%
1/16
|
0.00%
0/8
|
0.00%
0/14
|
|
Pregnancy, puerperium and perinatal conditions
Infection of amniotic cavity
|
0.00%
0/16
|
0.00%
0/8
|
7.1%
1/14
|
|
Pregnancy, puerperium and perinatal conditions
Pruritus
|
0.00%
0/16
|
0.00%
0/8
|
7.1%
1/14
|
|
Pregnancy, puerperium and perinatal conditions
Sleep disturbance
|
6.2%
1/16
|
0.00%
0/8
|
0.00%
0/14
|
|
Pregnancy, puerperium and perinatal conditions
Sleep apnea
|
6.2%
1/16
|
0.00%
0/8
|
0.00%
0/14
|
|
Pregnancy, puerperium and perinatal conditions
Edema localized
|
6.2%
1/16
|
0.00%
0/8
|
0.00%
0/14
|
|
Pregnancy, puerperium and perinatal conditions
Glycosuria
|
6.2%
1/16
|
0.00%
0/8
|
0.00%
0/14
|
|
Pregnancy, puerperium and perinatal conditions
Musculoskeletal Pain
|
0.00%
0/16
|
0.00%
0/8
|
7.1%
1/14
|
|
Pregnancy, puerperium and perinatal conditions
Pregnancy-induced Hypertension
|
12.5%
2/16
|
0.00%
0/8
|
0.00%
0/14
|
|
Pregnancy, puerperium and perinatal conditions
Pulmonary collapse
|
6.2%
1/16
|
0.00%
0/8
|
0.00%
0/14
|
|
Pregnancy, puerperium and perinatal conditions
Postpartum depression
|
0.00%
0/16
|
12.5%
1/8
|
0.00%
0/14
|
|
Pregnancy, puerperium and perinatal conditions
Postpartum infection
|
6.2%
1/16
|
0.00%
0/8
|
0.00%
0/14
|
|
Pregnancy, puerperium and perinatal conditions
Neonatal Jaundice
|
16.7%
2/12
|
20.0%
1/5
|
33.3%
4/12
|
|
Pregnancy, puerperium and perinatal conditions
Intrauterine growth restriction
|
8.3%
1/12
|
0.00%
0/5
|
8.3%
1/12
|
|
Pregnancy, puerperium and perinatal conditions
Neonatal infection
|
0.00%
0/12
|
0.00%
0/5
|
8.3%
1/12
|
|
Pregnancy, puerperium and perinatal conditions
Other complication of infant after delivery
|
0.00%
0/12
|
0.00%
0/5
|
8.3%
1/12
|
Additional Information
Richard S. Legro, M.D.
Penn State College of Medicine, Penn State Milton S. Hershey Medical Center
Phone: 717-531-8478
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place