PCOS
Conditions
Brief summary
Increased insulin levels leads to increased secretion of D-chiro inositol(DCI) from the kidneys in women with PCOS, but not in normal women. This leads to a reduction in circulating DCI and insulin stimulated release of DCI-IPG.To determine if decreasing circulating insulin directly by inhibition of islet insulin release with diazoxide in obese women with PCOS 1)decreases the renal clearance of DCI and 2) increases the circulating concentration of DCI.
Interventions
DRUGdiazoxide
100mg orally three times per day for 10 days
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Virginia Commonwealth University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Obese women with PCOS and normal women aged 18-40, * PCOS less than 8 periods/year, elevated total or free testosterone, normal thyroid function tests and serum prolactin, exclusion of adrenal hyperplasia * Normal regular monthly periods, no clinical evidence of androgen excess, * All Acceptable health on interview, medical history, physical exams and lab tests, signed, witnessed informed consent and ability to comply to study requirements
Exclusion criteria
* DM, clinically significant pulmonary, cardiac, renal, hepatic, neurologic, psychiatric, infectious, neoplastic or malignant disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Renal Clearance of D-chiroinositol (DCI) at 12 Days | 12 days | Following inhibition of insulin release using diazoxide, measured renal clearance of D-chiro inositol (DCI) via urinary Chiro-inositol dci assay |
| Level of Circulating D-chiro Inositol (DCI) | 12 days | Measured circulating concentration of plasma DCI following inhibition of insulin release using diazoxide |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PCOS Subjects PCOS subjects given diazoxide
diazoxide: 100mg orally three times per day for 10 days | 8 |
| Normal Subjects Normal subjects given diazoxide
diazoxide: 100mg orally three times per day for 10 days | 9 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 3 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | PCOS Subjects | Normal Subjects | Total |
|---|---|---|---|
| 24-h urinary D-chiroinositol (DCI) (nmol/day) | 1808 nmol/day | 1448 nmol/day | 1628 nmol/day |
| 24-h urinary MYO (nmol/day) | 52866 nmol/day | 78909 nmol/day | 65888 nmol/day |
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 9 Participants | 17 Participants |
| Area under the curve (AUC) glucose (mg*min/dL) | 16447 mg*min/dL | 13168 mg*min/dL | 14808 mg*min/dL |
| AUC insulin (mg*min/ml) | 8351 mg*min/ml | 5284 mg*min/ml | 6818 mg*min/ml |
| BMI (Body Mass Index) | 41.0 kg/m^2 | 38.4 kg/m^2 | 39.7 kg/m^2 |
| Fasting glucose (mg/dl) | 85.3 mg/dl | 84.2 mg/dl | 84.8 mg/dl |
| Fasting insulin (ulU/mL) | 9.4 ulU/mL | 6.8 ulU/mL | 8.1 ulU/mL |
| Free testosterone (pmol/L) | 144.3 pmol/L | 57.7 pmol/L | 101 pmol/L |
| Plasma DCI (nmol/mL) | 0.36 nmol/mL | 0.33 nmol/mL | 0.35 nmol/mL |
| Plasma myo-Inositol (MYO) (nmol/mL) | 19.7 nmol/mL | 23.1 nmol/mL | 21.4 nmol/mL |
| Region of Enrollment United States | 8 participants | 9 participants | 17 participants |
| Sex: Female, Male Female | 8 Participants | 9 Participants | 17 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Sex hormone binding globulin (SHBG) (nmol/L) | 32.1 nmol/L | 45.6 nmol/L | 38.9 nmol/L |
| Total testosterone (ng/mL) | 2.2 ng/mL | 1.1 ng/mL | 1.7 ng/mL |
| uCI MYO (ml/min) | 1.91 ml/min | 2.43 ml/min | 2.17 ml/min |
| Urinary clearance (uCl) DCI (ml/min) | 3.46 ml/min | 3.02 ml/min | 3.24 ml/min |
| Waist-to-hip ratio (WHR) | 0.84 unitless | 0.78 unitless | 0.81 unitless |
| Whole Body Insulin Sensitivity Index | 4.76 units on a scale | 6.90 units on a scale | 5.83 units on a scale |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 8 | 0 / 9 |
| serious Total, serious adverse events | 0 / 8 | 0 / 9 |
Outcome results
Primary
Level of Circulating D-chiro Inositol (DCI)
Measured circulating concentration of plasma DCI following inhibition of insulin release using diazoxide
Time frame: 12 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| PCOS Subjects | Level of Circulating D-chiro Inositol (DCI) | 0.27 nmol/mL |
| Normal Subjects | Level of Circulating D-chiro Inositol (DCI) | 0.27 nmol/mL |
Primary
Renal Clearance of D-chiroinositol (DCI) at 12 Days
Following inhibition of insulin release using diazoxide, measured renal clearance of D-chiro inositol (DCI) via urinary Chiro-inositol dci assay
Time frame: 12 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| PCOS Subjects | Renal Clearance of D-chiroinositol (DCI) at 12 Days | 4.75 ml/min |
| Normal Subjects | Renal Clearance of D-chiroinositol (DCI) at 12 Days | 5.16 ml/min |