Insulin and Polycystic Ovary Syndrome

• Sponsor: Virginia Commonwealth University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00683774
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)
• Enrollment: 21
• Location: 1
• Arms: 2
• Duration (Months): 37
• Patients Per Site Per Month: 0.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
PCOS	Drug: diazoxide	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Determination if Direct Inhibition of Insulin Release With Diazoxide Decreases Renal Clearance of D-Chiroinositol (DCI) and Increases Circulating DCI in Obese Women With Polycystic Ovary Syndrome (PCOS)
• Study Start Date: Nov 1, 2005
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PCOS subjects PCOS subjects given diazoxide	Drug: diazoxide; 100mg orally three times per day for 10 days
Active Comparator: Normal subjects Normal subjects given diazoxide	Drug: diazoxide; 100mg orally three times per day for 10 days

Outcome Measures

Primary Outcome Measures

1. 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

2. Level of Circulating D-chiro Inositol (DCI) [12 days]

   Measured circulating concentration of plasma DCI following inhibition of insulin release using diazoxide

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 40 Years
• Sexes Eligible for Study: Female
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	General Clinical Research Center	Richmond	Virginia	United States	23298

Sponsors and Collaborators

• Virginia Commonwealth University
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

• Principal Investigator: John E. Nestler, MD, Virginia Commonwealth University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Virginia Commonwealth University
• ClinicalTrials.gov Identifier: NCT00683774
• Other Study ID Numbers: VCU IRB 4479; 2R01HD035629-09A2
• First Posted: May 23, 2008
• Last Update Posted: Jun 14, 2017
• Last Verified: Jun 1, 2017

• Additional relevant MeSH terms: Polycystic Ovary Syndrome; Diazoxide

Study Results

Participant Flow

Arm/Group Title	PCOS Subjects	Normal Subjects
Arm/Group Description	PCOS subjects given diazoxide diazoxide: 100mg orally three times per day for 10 days	Normal subjects given diazoxide diazoxide: 100mg orally three times per day for 10 days
Period Title: Overall Study
STARTED	11	10
COMPLETED	8	9
NOT COMPLETED	3	1

Baseline Characteristics

Arm/Group Title	PCOS Subjects	Normal Subjects	Total
Arm/Group Description	PCOS subjects given diazoxide diazoxide: 100mg orally three times per day for 10 days	Normal subjects given diazoxide diazoxide: 100mg orally three times per day for 10 days	Total of all reporting groups
Overall Participants	8	9	17
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	8 100%	9 100%	17 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	8 100%	9 100%	17 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	8 100%	9 100%	17 100%
BMI (Body Mass Index) (kg/m^2) [Mean (Full Range) ]
Mean (Full Range) [kg/m^2]	41.0	38.4	39.7
Waist-to-hip ratio (WHR) (unitless) [Mean (Full Range) ]
Mean (Full Range) [unitless]	0.84	0.78	0.81
Sex hormone binding globulin (SHBG) (nmol/L) (nmol/L) [Mean (Full Range) ]
Mean (Full Range) [nmol/L]	32.1	45.6	38.9
Total testosterone (ng/mL) (ng/mL) [Mean (Full Range) ]
Mean (Full Range) [ng/mL]	2.2	1.1	1.7
Free testosterone (pmol/L) (pmol/L) [Mean (Full Range) ]
Mean (Full Range) [pmol/L]	144.3	57.7	101
Fasting glucose (mg/dl) (mg/dl) [Mean (Full Range) ]
Mean (Full Range) [mg/dl]	85.3	84.2	84.8
Fasting insulin (ulU/mL) (ulU/mL) [Mean (Full Range) ]
Mean (Full Range) [ulU/mL]	9.4	6.8	8.1
Area under the curve (AUC) glucose (mg*min/dL) (mg*min/dL) [Mean (Full Range) ]
Mean (Full Range) [mg*min/dL]	16447	13168	14808
AUC insulin (mg*min/ml) (mg*min/ml) [Mean (Full Range) ]
Mean (Full Range) [mg*min/ml]	8351	5284	6818
Whole Body Insulin Sensitivity Index (units on a scale) [Mean (Full Range) ]
Mean (Full Range) [units on a scale]	4.76	6.90	5.83
Plasma DCI (nmol/mL) (nmol/mL) [Mean (Full Range) ]
Mean (Full Range) [nmol/mL]	0.36	0.33	0.35
24-h urinary D-chiroinositol (DCI) (nmol/day) (nmol/day) [Mean (Full Range) ]
Mean (Full Range) [nmol/day]	1808	1448	1628
Urinary clearance (uCl) DCI (ml/min) (ml/min) [Mean (Full Range) ]
Mean (Full Range) [ml/min]	3.46	3.02	3.24
Plasma myo-Inositol (MYO) (nmol/mL) (nmol/mL) [Mean (Full Range) ]
Mean (Full Range) [nmol/mL]	19.7	23.1	21.4
24-h urinary MYO (nmol/day) (nmol/day) [Mean (Full Range) ]
Mean (Full Range) [nmol/day]	52866	78909	65888
uCI MYO (ml/min) (ml/min) [Mean (Full Range) ]
Mean (Full Range) [ml/min]	1.91	2.43	2.17

Outcome Measures

1. Primary Outcome

Title	Renal Clearance of D-chiroinositol (DCI) at 12 Days
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PCOS Subjects	Normal Subjects
Arm/Group Description	PCOS subjects given diazoxide diazoxide: 100mg orally three times per day for 10 days	Normal subjects given diazoxide diazoxide: 100mg orally three times per day for 10 days
Measure Participants	8	9
Mean (Full Range) [ml/min]	4.75	5.16

2. Primary Outcome

Title	Level of Circulating D-chiro Inositol (DCI)
Description	Measured circulating concentration of plasma DCI following inhibition of insulin release using diazoxide
Time Frame	12 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PCOS Subjects	Normal Subjects
Arm/Group Description	PCOS subjects given diazoxide diazoxide: 100mg orally three times per day for 10 days	Normal subjects given diazoxide diazoxide: 100mg orally three times per day for 10 days
Measure Participants	8	9
Mean (Full Range) [nmol/mL]	0.27	0.27

Adverse Events

Time Frame	1 year
Arm/Group Title	PCOS Subjects		Normal Subjects
Arm/Group Description	PCOS subjects given diazoxide diazoxide: 100mg orally three times per day for 10 days		Normal subjects given diazoxide diazoxide: 100mg orally three times per day for 10 days
All Cause Mortality
	PCOS Subjects		Normal Subjects
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	PCOS Subjects		Normal Subjects
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/9 (0%)
Other (Not Including Serious) Adverse Events
	PCOS Subjects		Normal Subjects
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/9 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.