Obstructive Sleep Apnea, Polycystic Ovary Syndrome
Conditions
Keywords
polycystic ovary syndrome, metabolic syndrome, obstructive sleep apnea, impaired glucose tolerance, insulin resistance
Brief summary
Polycystic ovary syndrome (PCOS) affects 5-10% of women in the United States. Its onset is usually at the time of puberty with manifestations of menstrual irregularity, hirsutism, and obesity. Women with PCOS suffer at an early stage of adulthood from all of the components of the metabolic syndrome, a syndrome that typically has its peak in mid-life in other subject populations. Women with PCOS are more insulin resistant than weight-matched control women and have exceptionally high rates of early-onset impaired glucose tolerance and type 2 diabetes, as well as a substantially elevated risk for hypertension, dyslipidemia, coronary, and other vascular diseases. While recent evidence indicates that the prevalence of sleep-disordered breathing (SDB) is 30-40 fold higher in PCOS than in weight-matched control women, the possible role of SDB in causing the increased metabolic and cardiovascular risks of PCOS has not been evaluated. The overall objective of the proposed study is to analyze the direction of causality between sleep disturbances and markers of the metabolic syndrome in PCOS.
Detailed description
Polycystic ovary syndrome (PCOS) affects 5-10% of women and may be viewed as the combination of hyperandrogenism with the classical features of the metabolic syndrome in young women. PCOS presents a unique opportunity to dissect the relationship between metabolic and cardiovascular risk and sleep disordered breathing (SDB) in a population where intrinsic effects of aging have not yet developed. Because a relationship between obstructive sleep apnea, insulin resistance and elevated testosterone levels has also been observed in men and in women without PCOS, insights gained from studies in PCOS will have broad implications. The Specific Aims of the present application are: Specific Aim 1: to test the hypothesis that sleep disturbances are caused by hyperandrogenemia and hyperinsulinemia that characterize PCOS. Following a detailed baseline evaluation of sleep, hormonal, metabolic and cardiovascular parameters, women with PCOS will be randomized to an 8-week treatment phase with pioglitazone or depot leuprolide plus estrogen/progestin replacement or placebo. Pioglitazone will reduce insulin levels, and consequently androgen levels, in PCOS. We will compare the effects of androgen reduction alone (depot leuprolide plus estrogen/progestin) to those of insulin plus androgen reduction achieved with pioglitazone. Primary comparisons will be the change in sleep parameters from baseline between: placebo & pioglitazone; placebo & leuprolide/estrogen/progestin; pioglitazone & leuprolide/estrogen/progestin. Specific Aim 2: to test the hypothesis that sleep disturbances cause the hormonal, metabolic and cardiovascular alterations seen in women with PCOS. PCOS women with SDB and matched control women with SDB will be evaluated at baseline and following 8 weeks of CPAP treatment. The primary comparison will be between baseline and post-treatment parameters in PCOS women. The secondary comparison will be the post-treatment change from baseline between PCOS and control women to test the hypothesis that for the same degree in improvement in SDB, the magnitude of change in metabolic and cardiovascular measures will be greater in PCOS than in controls. Specific Aim 3: to test the hypothesis that in normal young women, experimental manipulation of sleep that recapitulates the sleep disturbances characteristic of women with PCOS will result in metabolic, hormonal, and cardiovascular alterations that are typical of the metabolic syndrome. A group of healthy young women will be studied twice using a randomized cross-over design. In one study, rapid eye movement (REM) sleep will be fragmented by experimentally induced microarousals for 3 consecutive nights and non-REM sleep will be left undisturbed. In the other, slow wave activity will be suppressed without awakening the subject and REM sleep will be left undisturbed. Each study will be preceded by 2 nights of baseline sleep. Results were not reported for Aim 3 since no devices or drugs were tested in this aim.
Interventions
DEVICEcontinuous positive airway pressure (CPAP)
CPAP is the most effective treatment available for sleep disordered breathing. CPAP provides a constant, controllable pressure to keep your upper airway open during sleep so that you can breathe normally. The pressure acts much in the same way as a splint and holds the airway open.
DRUGdepot leuprolide plus estrogen/progestin replacement
Depot leuprolide is a long-acting, modified version of the natural brain hormone, gonadotropin releasing hormone (GnRH). This study drug will temporarily reduce the pituitary hormones that stimulate the ovaries to make both female (estrogen) and male (testosterone) hormones. The effect of this study drug will last approximately 12 weeks. During this time, your female hormone levels will be brought to normal by the use of a patch that contains estrogen and progesterone. This patch is placed on the skin and is changed twice a week. The subject will continue to wear this patch for 4 weeks after the end of the study, until the effects of the Lupron injection wear off.
DRUGpioglitazone
Pioglitazone (Actos). Pioglitazone is an oral medication approved in the Unites States for the treatment of patients with type 2 diabetes (however it is not approved for studies in this protocol). This is one of a class of drugs known as thiazolidinediones. This class of drugs has been associated with potential beneficial changes in the metabolism (use of glucose by the body) as well as lipids (fats) in the blood.
PROCEDUREREM frag
Rapid eye movement (REM) sleep will be fragmented by experimentally induced microarousals for 3 consecutive nights and non-REM sleep will be left undisturbed.
PROCEDURESWS supp
SWS: Slow wave activity will be suppressed without awakening the subject and REM sleep will be left undisturbed.
Sponsors
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
University of Chicago
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* PCOS subjects will be recruited from the Endocrinology Clinics of the University of Chicago. All will be at least 2 years post-menarche and less than 40 years of age. A diagnosis of PCOS will require: * the presence of oligo/amenorrhea; * hyperandrogenemia, defined by a supranormal plasma free testosterone level (\> 10 pg/ml); * hyperandrogenism, as evidenced by infertility, hirsutism, acne, or androgenetic alopecia; and * exclusion of nonclassic 21-hydroxylase deficiency congenital adrenal hyperplasia, Cushing's syndrome, hypothyroidism, or significant elevations in serum prolactin. Thus, all subjects will meet the National Institutes of Health (NIH) consensus criteria for PCOS. * Control subjects will be matched, as closely as possible, for age, ethnicity, body mass index (BMI), and body fat distribution \[as assessed by single cut abdominal computed tomography (CT) scan and dual energy x-ray absorptiometry (DEXA) scan\]. * Normal lean (BMI \<25 kg/m2) women will be between 18 and 40 years of age, in good health, with normal menstrual cycles, no sleep complaints, no history of endocrine disorder. All studies will be initiated in the early follicular phase (days 2-4).
Exclusion criteria
* For at least 2 months before the study, all subjects (PCOS and control) must not take steroid preparations (including oral contraceptives), medications known to alter insulin secretion and/or action, or medications known to influence sleep.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Aim 3: Insulin Sensitivity Index (SI) From Intravenous Glucose Tolerance Test [After 3 Nights of SWS Suppression] | 3 nights | 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. |
| Aim 1: Apnea-Hypopnea Index (AHI) [Baseline] | baseline | 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. |
| Aim 1: Apnea-hypopnea Index (AHI) [After Treatment] | 8 weeks | 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. |
| Aim 2: Insulin Sensitivity Index (SI) From Intravenous Glucose Tolerance Test [Baseline] | baseline (0 weeks) | 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. |
| Aim 2: Insulin Sensitivity Index (SI) From Intravenous Glucose Tolerance Test [After CPAP] | 8 weeks | 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. |
| Aim 2: Acute Insulin Resistance to Intravenous Glucose (AIRg) [Baseline] | baseline (0 weeks) | 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. |
| Aim 2: Acute Insulin Resistance to Intravenous Glucose (AIRg) [After CPAP] | 8 weeks | 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. |
| Aim 3: Insulin Sensitivity Index (SI) From Intravenous Glucose Tolerance Test [Baseline] | Baseline | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Aim 1: Blood Pressure [Baseline] | baseline (0 weeks) | Blood pressure is the pressure of blood within the arteries, produced primarily by the contraction of the heart muscle. |
| Aim 1: Blood Pressure [After Treatment] | 8 weeks | Blood pressure is the pressure of blood within the arteries, produced primarily by the contraction of the heart muscle. |
| Aim 1: Visceral Adiposity [Baseline] | up to half of an hour | Visceral adiposity refers to the degree of fat located in the peritoneal cavity (abdominal area) that surrounds the body's internal organs. |
| Aim 1: Visceral Adiposity [After Treatment] | up to half of an hour | Visceral adiposity refers to the degree of fat located in the peritoneal cavity (abdominal area) that surrounds the body's internal organs. |
| Aim 2: Mean Cortisol Levels Over 24 Hours, Per Patient [Baseline] | 10 minutes, over a period of 24 hours | 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. |
| Aim 2: Mean Cortisol Levels Over 24 Hours, Per Patient [After Treatment] | 10 minutes, over a period of 24 hours | 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. |
| Aim 2: Mean Leptin Levels Over 24 Hours, Per Patient [Baseline] | 15 minutes over a period of 24 hours | 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. |
| Aim 2: Mean Leptin Levels Over 24 Hours, Per Patient [After Treatment] | 15 minutes over a period of 24 hours | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aim 1: Placebo One of the 3 treatment arms in Aim 1: Placebo. No subjects were randomized to this arm. | 0 |
| Aim 1: Pioglitazone One of the 3 treatment arms in Aim 1: Pioglitazone. No subjects were randomized to this arm. | 0 |
| 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. | 0 |
| 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). | 19 |
| 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). | 4 |
| Aim 3: All Participants Includes groups randomized to any experimental ordering in Aim 3 | 14 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | CPAP machine malfunction | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 6 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Scheduling issue | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Aim 2: PCOS + SDB With CPAP | Aim 2: Matched Controls With CPAP | Aim 3: All Participants | Total |
|---|---|---|---|---|
| Age, Continuous | 31.2 years STANDARD_DEVIATION 5.3 | 32.2 years STANDARD_DEVIATION 5.8 | 24.6 years STANDARD_DEVIATION 2.7 | 28.8 years STANDARD_DEVIATION 4.4 |
| Sex: Female, Male Female | 19 Participants | 4 Participants | 5 Participants | 28 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 9 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 1 / 19 | 0 / 4 | 0 / 14 | 0 / 14 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 19 | 0 / 4 | 0 / 14 | 0 / 14 |
Outcome results
Primary
Aim 1: Apnea-hypopnea Index (AHI) [After Treatment]
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.
Time frame: 8 weeks
Population: No participants were randomized to these study arms.
Primary
Aim 1: Apnea-Hypopnea Index (AHI) [Baseline]
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.
Time frame: baseline
Population: No participants were randomized to these study arms.
Primary
Aim 2: Acute Insulin Resistance to Intravenous Glucose (AIRg) [After CPAP]
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aim 1: Placebo | Aim 2: Acute Insulin Resistance to Intravenous Glucose (AIRg) [After CPAP] | 1614 mU/(liter x min) | Standard Error 385 |
| Aim 1: Pioglitazone | Aim 2: Acute Insulin Resistance to Intravenous Glucose (AIRg) [After CPAP] | 722 mU/(liter x min) | Standard Error 211 |
Primary
Aim 2: Acute Insulin Resistance to Intravenous Glucose (AIRg) [Baseline]
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aim 1: Placebo | Aim 2: Acute Insulin Resistance to Intravenous Glucose (AIRg) [Baseline] | 1711 mU/(liter x min) | Standard Error 370 |
| Aim 1: Pioglitazone | Aim 2: Acute Insulin Resistance to Intravenous Glucose (AIRg) [Baseline] | 695 mU/(liter x min) | Standard Error 228 |
Primary
Aim 2: Insulin Sensitivity Index (SI) From Intravenous Glucose Tolerance Test [After CPAP]
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aim 1: Placebo | Aim 2: Insulin Sensitivity Index (SI) From Intravenous Glucose Tolerance Test [After CPAP] | 0.93 mU/(liter x min) | Standard Error 0.17 |
| Aim 1: Pioglitazone | Aim 2: Insulin Sensitivity Index (SI) From Intravenous Glucose Tolerance Test [After CPAP] | 2.57 mU/(liter x min) | Standard Error 0.34 |
Primary
Aim 2: Insulin Sensitivity Index (SI) From Intravenous Glucose Tolerance Test [Baseline]
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aim 1: Placebo | Aim 2: Insulin Sensitivity Index (SI) From Intravenous Glucose Tolerance Test [Baseline] | 0.87 mU/(liter x min) | Standard Error 0.13 |
| Aim 1: Pioglitazone | Aim 2: Insulin Sensitivity Index (SI) From Intravenous Glucose Tolerance Test [Baseline] | 3.67 mU/(liter x min) | Standard Error 1.01 |
Primary
Aim 3: Insulin Sensitivity Index (SI) From Intravenous Glucose Tolerance Test [After 3 Nights of SWS Suppression]
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aim 1: Pioglitazone | 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 |
Primary
Aim 3: Insulin Sensitivity Index (SI) From Intravenous Glucose Tolerance Test [Baseline]
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aim 1: Pioglitazone | Aim 3: Insulin Sensitivity Index (SI) From Intravenous Glucose Tolerance Test [Baseline] | 8.42 mU/(liter x min) | Standard Error 1.12 |
Secondary
Aim 1: Blood Pressure [After Treatment]
Blood pressure is the pressure of blood within the arteries, produced primarily by the contraction of the heart muscle.
Time frame: 8 weeks
Population: No participants were randomized to these study arms.
Secondary
Aim 1: Blood Pressure [Baseline]
Blood pressure is the pressure of blood within the arteries, produced primarily by the contraction of the heart muscle.
Time frame: baseline (0 weeks)
Population: No participants were randomized to these study arms.
Secondary
Aim 1: Visceral Adiposity [After Treatment]
Visceral adiposity refers to the degree of fat located in the peritoneal cavity (abdominal area) that surrounds the body's internal organs.
Time frame: up to half of an hour
Population: No participants were randomized to this arm.
Secondary
Aim 1: Visceral Adiposity [Baseline]
Visceral adiposity refers to the degree of fat located in the peritoneal cavity (abdominal area) that surrounds the body's internal organs.
Time frame: up to half of an hour
Population: No participants were randomized to this arm.
Secondary
Aim 2: Mean Cortisol Levels Over 24 Hours, Per Patient [After Treatment]
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aim 1: Placebo | Aim 2: Mean Cortisol Levels Over 24 Hours, Per Patient [After Treatment] | 7.8 microgram/deciliter | Standard Error 0.5 |
| Aim 1: Pioglitazone | Aim 2: Mean Cortisol Levels Over 24 Hours, Per Patient [After Treatment] | 6.5 microgram/deciliter | Standard Error 0.2 |
Secondary
Aim 2: Mean Cortisol Levels Over 24 Hours, Per Patient [Baseline]
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aim 1: Placebo | Aim 2: Mean Cortisol Levels Over 24 Hours, Per Patient [Baseline] | 8.6 microgram/deciliter | Standard Error 0.9 |
| Aim 1: Pioglitazone | Aim 2: Mean Cortisol Levels Over 24 Hours, Per Patient [Baseline] | 6.1 microgram/deciliter | Standard Error 0.2 |
Secondary
Aim 2: Mean Leptin Levels Over 24 Hours, Per Patient [After Treatment]
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aim 1: Placebo | Aim 2: Mean Leptin Levels Over 24 Hours, Per Patient [After Treatment] | 65.8 nanogram/milliliter | Standard Error 9.9 |
| Aim 1: Pioglitazone | Aim 2: Mean Leptin Levels Over 24 Hours, Per Patient [After Treatment] | 57.4 nanogram/milliliter | Standard Error 2.3 |
Secondary
Aim 2: Mean Leptin Levels Over 24 Hours, Per Patient [Baseline]
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aim 1: Placebo | Aim 2: Mean Leptin Levels Over 24 Hours, Per Patient [Baseline] | 67.6 nanogram/milliliter | Standard Error 10.5 |
| Aim 1: Pioglitazone | Aim 2: Mean Leptin Levels Over 24 Hours, Per Patient [Baseline] | 56.9 nanogram/milliliter | Standard Error 1.6 |