Trial Outcomes & Findings for Polycystic Ovary Syndrome (PCOS) and Sleep Apnea (NCT NCT00203996)

Results Overview

Insulin sensitivity Index (SI) is the increase in net fractional glucose clearance rate per unit change in plasma insulin concentration after an intravenous glucose load. SI quantifies the capacity of insulin to promote glucose disposal.

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

37 participants

Primary outcome timeframe

Baseline

Results posted on

2023-03-21

Participant Flow

Participant milestones

Participant milestones
Measure	Aim 2: PCOS + SDB With CPAP One of the 2 study groups in Aim 2: Women with polycystic ovary syndrome (PCOS) and sleep disordered breathing (SDB) were treated with 8 weeks of continuous positive airway pressure (CPAP).	Aim 2: Matched Controls With CPAP One of the 2 study groups in Aim 2: Women who were of similar age to those in the PCOS+SDB group were treated with 8 weeks of continuous positive airway pressure (CPAP).	Aim 3: REM Frag - SWS Supp - Baseline Each subject was assessed under three experimental conditions in the following order. REM fragmentation: Rapid eye movement (REM) sleep will be fragmented by experimentally induced microarousals for 3 consecutive nights and non-REM sleep will be left undisturbed. SWS suppression: Slow wave activity will be suppressed without awakening the subject and REM sleep will be left undisturbed. Baseline: "Baseline" sleep (i.e., with no experimental intervention) assessment is recorded. This assessment may have been recorded as the first, second, or third intervention.	Aim 3: REM Frag - Baseline - SWS Supp Each subject was assessed under three experimental conditions in the following order. REM fragmentation: Rapid eye movement (REM) sleep will be fragmented by experimentally induced microarousals for 3 consecutive nights and non-REM sleep will be left undisturbed. Baseline: "Baseline" sleep (i.e., with no experimental intervention) assessment is recorded. This assessment may have been recorded as the first, second, or third intervention. SWS suppression: Slow wave activity will be suppressed without awakening the subject and REM sleep will be left undisturbed.	Aim 3: Baseline - REM Frag - SWS Supp Each subject was assessed under three experimental conditions in the following order. Baseline: "Baseline" sleep (i.e., with no experimental intervention) assessment is recorded. This assessment may have been recorded as the first, second, or third intervention. REM fragmentation: Rapid eye movement (REM) sleep will be fragmented by experimentally induced microarousals for 3 consecutive nights and non-REM sleep will be left undisturbed. SWS suppression: Slow wave activity will be suppressed without awakening the subject and REM sleep will be left undisturbed.	Aim 3: SWS Supp - REM Frag - Baseline Each subject was assessed under three experimental conditions in the following order. SWS suppression: Slow wave activity will be suppressed without awakening the subject and REM sleep will be left undisturbed. REM fragmentation: Rapid eye movement (REM) sleep will be fragmented by experimentally induced microarousals for 3 consecutive nights and non-REM sleep will be left undisturbed. Baseline: "Baseline" sleep (i.e., with no experimental intervention) assessment is recorded. This assessment may have been recorded as the first, second, or third intervention.	Aim 3: Baseline - SWS Supp - REM Frag Each subject was assessed under three experimental conditions in the following order. Baseline: "Baseline" sleep (i.e., with no experimental intervention) assessment is recorded. This assessment may have been recorded as the first, second, or third intervention. SWS suppression: Slow wave activity will be suppressed without awakening the subject and REM sleep will be left undisturbed. REM fragmentation: Rapid eye movement (REM) sleep will be fragmented by experimentally induced microarousals for 3 consecutive nights and non-REM sleep will be left undisturbed.
Overall Study STARTED	19	4	3	2	4	2	3
Overall Study Aim 3 Only: First Intervention	0	0	3	2	4	2	3
Overall Study Aim 3 Only: Washout	0	0	3	2	2	2	2
Overall Study Aim 3 Only: Second Intervention	0	0	3	2	2	2	2
Overall Study Aim 3 Only: Second Washout	0	0	3	2	2	2	2
Overall Study Aim 3 Only: Third Intervention	0	0	3	2	2	2	2
Overall Study COMPLETED	9	3	3	2	2	2	2
Overall Study NOT COMPLETED	10	1	0	0	2	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Aim 2: PCOS + SDB With CPAP One of the 2 study groups in Aim 2: Women with polycystic ovary syndrome (PCOS) and sleep disordered breathing (SDB) were treated with 8 weeks of continuous positive airway pressure (CPAP).	Aim 2: Matched Controls With CPAP One of the 2 study groups in Aim 2: Women who were of similar age to those in the PCOS+SDB group were treated with 8 weeks of continuous positive airway pressure (CPAP).	Aim 3: Baseline - REM Frag - SWS Supp Each subject was assessed under three experimental conditions in the following order. Baseline: "Baseline" sleep (i.e., with no experimental intervention) assessment is recorded. This assessment may have been recorded as the first, second, or third intervention. REM fragmentation: Rapid eye movement (REM) sleep will be fragmented by experimentally induced microarousals for 3 consecutive nights and non-REM sleep will be left undisturbed. SWS suppression: Slow wave activity will be suppressed without awakening the subject and REM sleep will be left undisturbed.	Aim 3: Baseline - SWS Supp - REM Frag Each subject was assessed under three experimental conditions in the following order. Baseline: "Baseline" sleep (i.e., with no experimental intervention) assessment is recorded. This assessment may have been recorded as the first, second, or third intervention. SWS suppression: Slow wave activity will be suppressed without awakening the subject and REM sleep will be left undisturbed. REM fragmentation: Rapid eye movement (REM) sleep will be fragmented by experimentally induced microarousals for 3 consecutive nights and non-REM sleep will be left undisturbed.
Overall Study Lost to Follow-up	1	0	0	0
Overall Study Protocol Violation	6	1	0	0
Overall Study Physician Decision	2	0	0	1
Overall Study CPAP machine malfunction	1	0	0	0
Overall Study Scheduling issue	0	0	2	0

Baseline Characteristics

Polycystic Ovary Syndrome (PCOS) and Sleep Apnea

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Aim 1: Placebo One of the 3 treatment arms in Aim 1: Placebo. No subjects were randomized to this arm.	Aim 1: Pioglitazone One of the 3 treatment arms in Aim 1: Pioglitazone. No subjects were randomized to this arm.	Aim 1: Leuprolide + Estrogen/Progestin One of the 3 treatment arms in Aim 1: Leuprolide + estrogen/progestin replacement. No subjects were randomized to this arm.	Aim 2: PCOS + SDB With CPAP n=19 Participants One of the 2 study groups in Aim 2: Women with polycystic ovary syndrome (PCOS) and sleep disordered breathing (SDB) were treated with 8 weeks of continuous positive airway pressure (CPAP).	Aim 2: Matched Controls With CPAP n=4 Participants One of the 2 study groups in Aim 2: Women who were of similar age to those in the PCOS+SDB group were treated with 8 weeks of continuous positive airway pressure (CPAP).	Aim 3: All Participants n=14 Participants Includes groups randomized to any experimental ordering in Aim 3	Total n=37 Participants Total of all reporting groups
Age, Continuous	—	—	—	31.2 years STANDARD_DEVIATION 5.3 • n=4 Participants	32.2 years STANDARD_DEVIATION 5.8 • n=21 Participants	24.6 years STANDARD_DEVIATION 2.7 • n=8 Participants	28.8 years STANDARD_DEVIATION 4.4 • n=8 Participants
Sex: Female, Male Female	—	—	—	19 Participants n=4 Participants	4 Participants n=21 Participants	5 Participants n=8 Participants	28 Participants n=8 Participants
Sex: Female, Male Male	—	—	—	0 Participants n=4 Participants	0 Participants n=21 Participants	9 Participants n=8 Participants	9 Participants n=8 Participants

PRIMARY outcome

Timeframe: baseline

Population: No participants were randomized to these study arms.

Apnea-hypopnea index (AHI) is an index used to assess the severity of sleep apnea based on the total number of complete cessations (apnea) and partial obstructions (hypopnea) of breathing occurring per hour of sleep.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 8 weeks

Population: No participants were randomized to these study arms.

Apnea-hypopnea index (AHI) is an index used to assess the severity of sleep apnea based on the total number of complete cessations (apnea) and partial obstructions (hypopnea) of breathing occurring per hour of sleep.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: baseline (0 weeks)

Population: The recruitment of control subjects for this protocol was hindered by the difficulty in finding subjects who met both inclusion and exclusion criteria. As a consequence, the sample size of control subjects was insufficient to allow for any meaningful conclusions to be drawn. Statistical analyses were not possible due to insufficient sample size.

Insulin sensitivity Index (SI) is the increase in net fractional glucose clearance rate per unit change in plasma insulin concentration after an intravenous glucose load. SI quantifies the capacity of insulin to promote glucose disposal.

Outcome measures

Outcome measures
Measure	Aim 1: Placebo n=9 Participants One of the 3 treatment arms in Aim 1: Placebo. No subjects were randomized to this arm.	Aim 1: Pioglitazone n=3 Participants One of the 3 treatment arms in Aim 1: Pioglitazone. No subjects were randomized to this arm.	Aim 1: Leuprolide + Estrogen/Progestin One of the 3 treatment arms in Aim 1: Leuprolide + estrogen/progestin replacement. No subjects were randomized to this arm.
Aim 2: Insulin Sensitivity Index (SI) From Intravenous Glucose Tolerance Test [Baseline]	0.87 mU/(liter x min) Standard Error 0.13	3.67 mU/(liter x min) Standard Error 1.01	—

PRIMARY outcome

Timeframe: 8 weeks

Population: The recruitment of control subjects for this protocol was hindered by the difficulty in finding subjects who met both inclusion and exclusion criteria. As a consequence, the sample size of control subjects was insufficient to allow for any meaningful conclusions to be drawn. Statistical analyses were not possible due to insufficient sample size.

Insulin sensitivity Index (SI) is the increase in net fractional glucose clearance rate per unit change in plasma insulin concentration after an intravenous glucose load. SI quantifies the capacity of insulin to promote glucose disposal.

Outcome measures

Outcome measures
Measure	Aim 1: Placebo n=9 Participants One of the 3 treatment arms in Aim 1: Placebo. No subjects were randomized to this arm.	Aim 1: Pioglitazone n=3 Participants One of the 3 treatment arms in Aim 1: Pioglitazone. No subjects were randomized to this arm.	Aim 1: Leuprolide + Estrogen/Progestin One of the 3 treatment arms in Aim 1: Leuprolide + estrogen/progestin replacement. No subjects were randomized to this arm.
Aim 2: Insulin Sensitivity Index (SI) From Intravenous Glucose Tolerance Test [After CPAP]	0.93 mU/(liter x min) Standard Error 0.17	2.57 mU/(liter x min) Standard Error 0.34	—

PRIMARY outcome

Timeframe: baseline (0 weeks)

Population: The recruitment of control subjects for this protocol was hindered by the difficulty in finding subjects who met both inclusion and exclusion criteria. As a consequence, the sample size of control subjects was insufficient to allow for any meaningful conclusions to be drawn. Statistical analyses were not possible due to insufficient sample size.

Acute insulin resistance to intravenous glucose (AIRg) is a measure of the secretion of insulin during the first 10 minutes after an intravenous glucose load. AIRg addresses adequacy of insulin secretion.

Outcome measures

Outcome measures
Measure	Aim 1: Placebo n=9 Participants One of the 3 treatment arms in Aim 1: Placebo. No subjects were randomized to this arm.	Aim 1: Pioglitazone n=3 Participants One of the 3 treatment arms in Aim 1: Pioglitazone. No subjects were randomized to this arm.	Aim 1: Leuprolide + Estrogen/Progestin One of the 3 treatment arms in Aim 1: Leuprolide + estrogen/progestin replacement. No subjects were randomized to this arm.
Aim 2: Acute Insulin Resistance to Intravenous Glucose (AIRg) [Baseline]	1711 mU/(liter x min) Standard Error 370	695 mU/(liter x min) Standard Error 228	—

PRIMARY outcome

Timeframe: 8 weeks

Population: The recruitment of control subjects for this protocol was hindered by the difficulty in finding subjects who met both inclusion and exclusion criteria. As a consequence, the sample size of control subjects was insufficient to allow for any meaningful conclusions to be drawn. Statistical analyses were not possible due to insufficient sample size.

Acute insulin resistance to intravenous glucose (AIRg) is a measure of the secretion of insulin during the first 10 minutes after an intravenous glucose load. AIRg addresses adequacy of insulin secretion.

Outcome measures

Outcome measures
Measure	Aim 1: Placebo n=9 Participants One of the 3 treatment arms in Aim 1: Placebo. No subjects were randomized to this arm.	Aim 1: Pioglitazone n=3 Participants One of the 3 treatment arms in Aim 1: Pioglitazone. No subjects were randomized to this arm.	Aim 1: Leuprolide + Estrogen/Progestin One of the 3 treatment arms in Aim 1: Leuprolide + estrogen/progestin replacement. No subjects were randomized to this arm.
Aim 2: Acute Insulin Resistance to Intravenous Glucose (AIRg) [After CPAP]	1614 mU/(liter x min) Standard Error 385	722 mU/(liter x min) Standard Error 211	—

PRIMARY outcome

Timeframe: Baseline

Population: Due to technical issues, REM fragmentation data were not analyzable. Technical issues also resulted in non-analyzable data for two subjects in the SWS suppression study, thereby decreasing the sample size from 11 to 9 subjects.

Insulin sensitivity Index (SI) is the increase in net fractional glucose clearance rate per unit change in plasma insulin concentration after an intravenous glucose load. SI quantifies the capacity of insulin to promote glucose disposal.

Outcome measures

Outcome measures
Measure	Aim 1: Placebo One of the 3 treatment arms in Aim 1: Placebo. No subjects were randomized to this arm.	Aim 1: Pioglitazone n=9 Participants One of the 3 treatment arms in Aim 1: Pioglitazone. No subjects were randomized to this arm.	Aim 1: Leuprolide + Estrogen/Progestin One of the 3 treatment arms in Aim 1: Leuprolide + estrogen/progestin replacement. No subjects were randomized to this arm.
Aim 3: Insulin Sensitivity Index (SI) From Intravenous Glucose Tolerance Test [Baseline]	—	8.42 mU/(liter x min) Standard Error 1.12	—

PRIMARY outcome

Timeframe: 3 nights

Population: Due to technical issues, REM fragmentation data were not analyzable. Technical issues also resulted in non-analyzable data for two subjects in the SWS suppression study, thereby decreasing the sample size from 11 to 9 subjects.

Insulin sensitivity Index (SI) is the increase in net fractional glucose clearance rate per unit change in plasma insulin concentration after an intravenous glucose load. SI quantifies the capacity of insulin to promote glucose disposal.

Outcome measures

Outcome measures
Measure	Aim 1: Placebo One of the 3 treatment arms in Aim 1: Placebo. No subjects were randomized to this arm.	Aim 1: Pioglitazone n=9 Participants One of the 3 treatment arms in Aim 1: Pioglitazone. No subjects were randomized to this arm.	Aim 1: Leuprolide + Estrogen/Progestin One of the 3 treatment arms in Aim 1: Leuprolide + estrogen/progestin replacement. No subjects were randomized to this arm.
Aim 3: Insulin Sensitivity Index (SI) From Intravenous Glucose Tolerance Test [After 3 Nights of SWS Suppression]	—	5.87 mU/(liter x min) Standard Error 0.74	—

SECONDARY outcome

Timeframe: baseline (0 weeks)

Population: No participants were randomized to these study arms.

Blood pressure is the pressure of blood within the arteries, produced primarily by the contraction of the heart muscle.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 8 weeks

Population: No participants were randomized to these study arms.

Blood pressure is the pressure of blood within the arteries, produced primarily by the contraction of the heart muscle.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to half of an hour

Population: No participants were randomized to this arm.

Visceral adiposity refers to the degree of fat located in the peritoneal cavity (abdominal area) that surrounds the body's internal organs.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to half of an hour

Population: No participants were randomized to this arm.

Visceral adiposity refers to the degree of fat located in the peritoneal cavity (abdominal area) that surrounds the body's internal organs.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 10 minutes, over a period of 24 hours

Population: The recruitment of control subjects for this protocol was hindered by the difficulty in finding subjects who met both inclusion and exclusion criteria. As a consequence, the sample size of control subjects was insufficient to allow for any meaningful conclusions to be drawn. Statistical analyses were not possible due to insufficient sample size.

This outcome is defined as the average concentration of cortisol (a glucocorticoid produced by the adrenal gland) in the blood, measured repeatedly over a 24 hour period in each patient individually.

Outcome measures

Outcome measures
Measure	Aim 1: Placebo n=9 Participants One of the 3 treatment arms in Aim 1: Placebo. No subjects were randomized to this arm.	Aim 1: Pioglitazone n=3 Participants One of the 3 treatment arms in Aim 1: Pioglitazone. No subjects were randomized to this arm.	Aim 1: Leuprolide + Estrogen/Progestin One of the 3 treatment arms in Aim 1: Leuprolide + estrogen/progestin replacement. No subjects were randomized to this arm.
Aim 2: Mean Cortisol Levels Over 24 Hours, Per Patient [Baseline]	8.6 microgram/deciliter Standard Error 0.9	6.1 microgram/deciliter Standard Error 0.2	—

SECONDARY outcome

Timeframe: 10 minutes, over a period of 24 hours

Population: The recruitment of control subjects for this protocol was hindered by the difficulty in finding subjects who met both inclusion and exclusion criteria. As a consequence, the sample size of control subjects was insufficient to allow for any meaningful conclusions to be drawn. Statistical analyses were not possible due to insufficient sample size.

This outcome is defined as the average concentration of cortisol (a glucocorticoid produced by the adrenal gland) in the blood, measured repeatedly over a 24 hour period in each patient individually.

Outcome measures

Outcome measures
Measure	Aim 1: Placebo n=9 Participants One of the 3 treatment arms in Aim 1: Placebo. No subjects were randomized to this arm.	Aim 1: Pioglitazone n=3 Participants One of the 3 treatment arms in Aim 1: Pioglitazone. No subjects were randomized to this arm.	Aim 1: Leuprolide + Estrogen/Progestin One of the 3 treatment arms in Aim 1: Leuprolide + estrogen/progestin replacement. No subjects were randomized to this arm.
Aim 2: Mean Cortisol Levels Over 24 Hours, Per Patient [After Treatment]	7.8 microgram/deciliter Standard Error 0.5	6.5 microgram/deciliter Standard Error 0.2	—

SECONDARY outcome

Timeframe: 15 minutes over a period of 24 hours

Population: The recruitment of control subjects for this protocol was hindered by the difficulty in finding subjects who met both inclusion and exclusion criteria. As a consequence, the sample size of control subjects was insufficient to allow for any meaningful conclusions to be drawn. Statistical analyses were not possible due to insufficient sample size.

This outcome is defined as the average concentration of leptin (a hormone produced by the fat cells that affects feeding behavior and appetite) in the blood, measured repeatedly over a 24 hour period in each patient individually.

Outcome measures

Outcome measures
Measure	Aim 1: Placebo n=9 Participants One of the 3 treatment arms in Aim 1: Placebo. No subjects were randomized to this arm.	Aim 1: Pioglitazone n=3 Participants One of the 3 treatment arms in Aim 1: Pioglitazone. No subjects were randomized to this arm.	Aim 1: Leuprolide + Estrogen/Progestin One of the 3 treatment arms in Aim 1: Leuprolide + estrogen/progestin replacement. No subjects were randomized to this arm.
Aim 2: Mean Leptin Levels Over 24 Hours, Per Patient [Baseline]	67.6 nanogram/milliliter Standard Error 10.5	56.9 nanogram/milliliter Standard Error 1.6	—

SECONDARY outcome

Timeframe: 15 minutes over a period of 24 hours

Population: The recruitment of control subjects for this protocol was hindered by the difficulty in finding subjects who met both inclusion and exclusion criteria. As a consequence, the sample size of control subjects was insufficient to allow for any meaningful conclusions to be drawn. Statistical analyses were not possible due to insufficient sample size.

This outcome is defined as the average concentration of leptin (a hormone produced by the fat cells that affects feeding behavior and appetite) in the blood, measured repeatedly over a 24 hour period in each patient individually.