Trial Outcomes & Findings for Study of Brain Function in Women With Insulin Resistant Polycystic Ovary Syndrome (NCT NCT00670800)
NCT ID: NCT00670800
Last Updated: 2014-05-21
Results Overview
Mu-opioid binding potential in left nucleus accumbens is measured before and after 4 months of Metformin treatment. Mu-opioid binding potential is measured in vivo with C11-carfentanil positron emission tomography in women with PCOS before and after 4 months of metformin treatment. Binding Potential is measured by the ratio of Mu-opioid receptor concentration (Bmax)/Receptor radiotracer (C11-carfentanil) affinity (Kd.) Control group was measured at baseline only.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
14 participants
Primary outcome timeframe
Baseline and after 4 months
Results posted on
2014-05-21
Participant Flow
Volunteers between the ages of 21 - 40 years were recruited from reproductive endocrinology clinic and newspapers. Women were excluded according to protocol exclusion criteria (see protocol)
Some potential subjects were excluded due to results of an oral glucose tolerance test (OGTT).
Participant milestones
| Measure |
Women Affected With PCOS - Metformin
The Polycystic Ovary Syndrome (PCOS) affected group is comprised of subjects with insulin resistant PCOS, defined as having irregular menstrual cycles and hyperandrogenism with other causes ruled out. Insulin resistance will be identified as fasting homeostasis model assessment insulin resistance (HOMA2-IR) of 60%S or less.
|
Women Controls Without PCOS
Control group is comprised of subjects without PCOS. These women have normal menstrual cycles and no evidence of insulin resistance (fasting HOMA2 IR of 80%S or more).
.
Exclusion criteria: left handedness, acute medical illness, uncorrected thyroid disease, diabetes, neurological disease, current psychiatric illness, smoking within the last 6 months, use of hormones within the last 2 months, pregnancy within the last 6 months, current or past history of substance abuse, use of corticosteroids (such as cortisol and prednisone), history of lactic acidosis (condition caused by the buildup of lactic acid in the body), heart, lung and kidney problems, liver disease, use of intravenous dyes, current cimetidine (Tagamet) use, use of medications that affect the brain (for example, codeine, anti-depressants, anti-psychotics).
|
|---|---|---|
|
Overall Study
STARTED
|
7
|
7
|
|
Overall Study
COMPLETED
|
7
|
5
|
|
Overall Study
NOT COMPLETED
|
0
|
2
|
Reasons for withdrawal
| Measure |
Women Affected With PCOS - Metformin
The Polycystic Ovary Syndrome (PCOS) affected group is comprised of subjects with insulin resistant PCOS, defined as having irregular menstrual cycles and hyperandrogenism with other causes ruled out. Insulin resistance will be identified as fasting homeostasis model assessment insulin resistance (HOMA2-IR) of 60%S or less.
|
Women Controls Without PCOS
Control group is comprised of subjects without PCOS. These women have normal menstrual cycles and no evidence of insulin resistance (fasting HOMA2 IR of 80%S or more).
.
Exclusion criteria: left handedness, acute medical illness, uncorrected thyroid disease, diabetes, neurological disease, current psychiatric illness, smoking within the last 6 months, use of hormones within the last 2 months, pregnancy within the last 6 months, current or past history of substance abuse, use of corticosteroids (such as cortisol and prednisone), history of lactic acidosis (condition caused by the buildup of lactic acid in the body), heart, lung and kidney problems, liver disease, use of intravenous dyes, current cimetidine (Tagamet) use, use of medications that affect the brain (for example, codeine, anti-depressants, anti-psychotics).
|
|---|---|---|
|
Overall Study
2 controls were insulin resistant
|
0
|
2
|
Baseline Characteristics
Study of Brain Function in Women With Insulin Resistant Polycystic Ovary Syndrome
Baseline characteristics by cohort
| Measure |
PCOS Affected Women - Metformin
n=7 Participants
Right handed women who don't smoke and who drink very little will be considered eligible. Women with the following conditions (exclusion criteria) may not participate: left handedness, acute medical illness, uncorrected thyroid disease, diabetes, neurological disease, current psychiatric illness, smoking within the last 6 months, use of hormones within the last 2 months, pregnancy within the last 6 months, current or past history of substance abuse, use of corticosteroids (such as cortisol and prednisone), history of lactic acidosis (condition caused by the buildup of lactic acid in the body), heart, lung and kidney problems, liver disease, use of intravenous dyes, current cimetidine (Tagamet) use, use of medications that affect the brain (for example, codeine, anti-depressants, anti-psychotics).
|
Normal Controls
n=5 Participants
Normal controls are matched for age and education and screened for insulin resistance. Controls will have HOMA2 IR of 80%S or greater, normal hormone levels, regular menstrual cycles, and lack hirsutism and acne. Exclusion criteria: Left handedness, acute medical illness, uncorrected thyroid disease, diabetes, neurological disease, current psychiatric illness, claustrophobia, contraindications to MRI (including pacemakers, pumps, surgical clips or metallic surgical devices), smoking within the last 6 months, use of hormones or insulin sensitizing mediation within the last 2 months, pregnancy within the last 6 months, current or past history of substance abuse, use of corticosteroids, cardiac or pulmonary insufficiency, active liver disease and transaminases elevations \>2.5 X normal values, renal insufficiency (plasma creatinine level ≥1.4 mg/dl), use of centrally acting medications, allergy to any opioid medication, 300 lbs maximum weight limit (which is the max
|
Total
n=12 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
7 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
26.3 years
STANDARD_DEVIATION 4 • n=5 Participants
|
26.6 years
STANDARD_DEVIATION 4 • n=7 Participants
|
26.4 years
STANDARD_DEVIATION 4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
7 participants
n=5 Participants
|
5 participants
n=7 Participants
|
12 participants
n=5 Participants
|
|
Weight
|
203.9 pounds (lbs)
n=5 Participants
|
123.7 pounds (lbs)
n=7 Participants
|
170.48 pounds (lbs)
n=5 Participants
|
|
BMI (Body Mass Index)
|
35.3 lbs/inch^2
n=5 Participants
|
23 lbs/inch^2
n=7 Participants
|
29.5 lbs/inch^2
n=5 Participants
|
|
Waist Circumference
|
102 cm
n=5 Participants
|
72 cm
n=7 Participants
|
92 cm
n=5 Participants
|
|
Free Testosterone
|
1.5 pg/ml
n=5 Participants
|
.5 pg/ml
n=7 Participants
|
1 pg/ml
n=5 Participants
|
|
Total Testosterone
|
.7 ng/ml
n=5 Participants
|
.36 ng/ml
n=7 Participants
|
.55 ng/ml
n=5 Participants
|
|
Total Cholesterol
|
157 mg/dl
n=5 Participants
|
179 mg/dl
n=7 Participants
|
174 mg/dl
n=5 Participants
|
|
DHEAS
|
200 ug/dl
n=5 Participants
|
189 ug/dl
n=7 Participants
|
191 ug/dl
n=5 Participants
|
|
HDL
|
47 mg/dl
n=5 Participants
|
76 mg/dl
n=7 Participants
|
55.5 mg/dl
n=5 Participants
|
|
Triglycerides
|
74 mg/dl
n=5 Participants
|
72 mg/dl
n=7 Participants
|
73 mg/dl
n=5 Participants
|
|
Fasting Insulin
|
21.4 uU/ml
n=5 Participants
|
8.1 uU/ml
n=7 Participants
|
17.25 uU/ml
n=5 Participants
|
|
Fasting Glucose
|
87 mg/dl
n=5 Participants
|
89 mg/dl
n=7 Participants
|
89 mg/dl
n=5 Participants
|
|
Homeostatic Model Assessment (HOMA)
|
36.6 % - percentage
n=5 Participants
|
95.4 % - percentage
n=7 Participants
|
46.65 % - percentage
n=5 Participants
|
|
HOMA-IR
|
2.7 mU/L
n=5 Participants
|
1 mU/L
n=7 Participants
|
2.150 mU/L
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and after 4 monthsPopulation: All 7 PCOS women completed the protocol and were included. 5 of 7 controls were included in this analysis. 2 controls were excluded from analysis because repeat baseline OGTT showed HOMA %S of \<80%.
Mu-opioid binding potential in left nucleus accumbens is measured before and after 4 months of Metformin treatment. Mu-opioid binding potential is measured in vivo with C11-carfentanil positron emission tomography in women with PCOS before and after 4 months of metformin treatment. Binding Potential is measured by the ratio of Mu-opioid receptor concentration (Bmax)/Receptor radiotracer (C11-carfentanil) affinity (Kd.) Control group was measured at baseline only.
Outcome measures
| Measure |
PCOS Affected Women Pre-Metformin (Baseline)
n=7 Participants
PCOS will be defined as meeting the criteria of irregular menstrual cycles and hyperandrogenism (on physical exam or laboratory testing), with other causes ruled out. Subjects with insulin resistant PCOS must meet criteria for insulin resistance based on the 2 hr OGTT (Oral Glucose Tolerance Test). Insulin resistance will be defined as fasting HOMA2 IR of 60%S or less.
|
PCOS Affected Women Post-Metformin (After 4 Months)
n=7 Participants
PCOS will be defined as meeting the criteria of irregular menstrual cycles and hyperandrogenism (on physical exam or laboratory testing), with other causes ruled out. Subjects with insulin resistant PCOS must meet criteria for insulin resistance based on the 2 hr OGTT (Oral Glucose Tolerance Test). Insulin resistance will be defined as fasting HOMA2 IR of 60%S or less.
|
Normal Controls
n=5 Participants
Normal controls will have HOMA2 IR of 80%S or greater, normal hormone levels, regular menstrual cycles (range 24 - 34 days), and lack hirsutism and acne. Control subjects are matched for age and education with the PCOS affected women. Control data is measured once (at baseline time frame) for the entire study.
|
|---|---|---|---|
|
Mu-opioid Binding Potential Measured in Left Nucleus Accumbens
|
1.95 ratio
Standard Deviation 0.17
|
1.65 ratio
Standard Deviation .27
|
1.53 ratio
Standard Deviation 0.28
|
PRIMARY outcome
Timeframe: Baseline and after 4 monthsPopulation: All 7 PCOS women were included, 2 controls were excluded because repeat baseline HOMA2-IR %S was \<80%.
Mu-opioid binding potential in right nucleus accumbens measured before and after 4 months of Metformin treatment. Mu-opioid binding potential is measured in vivo with C11-carfentanil positron emission tomography in women with PCOS before and after 4 months of metformin treatment. Binding Potential is measured by the ratio of Mu-opioid receptor concentration (Bmax)/Receptor radiotracer (C11-carfentanil) affinity (Kd.) Control group was measured at baseline only.
Outcome measures
| Measure |
PCOS Affected Women Pre-Metformin (Baseline)
n=7 Participants
PCOS will be defined as meeting the criteria of irregular menstrual cycles and hyperandrogenism (on physical exam or laboratory testing), with other causes ruled out. Subjects with insulin resistant PCOS must meet criteria for insulin resistance based on the 2 hr OGTT (Oral Glucose Tolerance Test). Insulin resistance will be defined as fasting HOMA2 IR of 60%S or less.
|
PCOS Affected Women Post-Metformin (After 4 Months)
n=7 Participants
PCOS will be defined as meeting the criteria of irregular menstrual cycles and hyperandrogenism (on physical exam or laboratory testing), with other causes ruled out. Subjects with insulin resistant PCOS must meet criteria for insulin resistance based on the 2 hr OGTT (Oral Glucose Tolerance Test). Insulin resistance will be defined as fasting HOMA2 IR of 60%S or less.
|
Normal Controls
n=5 Participants
Normal controls will have HOMA2 IR of 80%S or greater, normal hormone levels, regular menstrual cycles (range 24 - 34 days), and lack hirsutism and acne. Control subjects are matched for age and education with the PCOS affected women. Control data is measured once (at baseline time frame) for the entire study.
|
|---|---|---|---|
|
Mu-opioid Binding Potential Measured in Right Nucleus Accumbens
|
2.40 ratio
Standard Deviation .11
|
2.11 ratio
Standard Deviation 0.21
|
2.05 ratio
Standard Deviation 0.28
|
PRIMARY outcome
Timeframe: Baseline and after 4 monthsMu-opioid binding potential in left amygdala measured before and after 4 months of Metformin treatment. Mu-opioid binding potential is measured in vivo with C11-carfentanil positron emission tomography in women with PCOS before and after 4 months of metformin treatment. Binding Potential is measured by the ratio of Mu-opioid receptor concentration (Bmax)/Receptor radiotracer (C11-carfentanil) affinity (Kd.)
Outcome measures
| Measure |
PCOS Affected Women Pre-Metformin (Baseline)
n=7 Participants
PCOS will be defined as meeting the criteria of irregular menstrual cycles and hyperandrogenism (on physical exam or laboratory testing), with other causes ruled out. Subjects with insulin resistant PCOS must meet criteria for insulin resistance based on the 2 hr OGTT (Oral Glucose Tolerance Test). Insulin resistance will be defined as fasting HOMA2 IR of 60%S or less.
|
PCOS Affected Women Post-Metformin (After 4 Months)
n=7 Participants
PCOS will be defined as meeting the criteria of irregular menstrual cycles and hyperandrogenism (on physical exam or laboratory testing), with other causes ruled out. Subjects with insulin resistant PCOS must meet criteria for insulin resistance based on the 2 hr OGTT (Oral Glucose Tolerance Test). Insulin resistance will be defined as fasting HOMA2 IR of 60%S or less.
|
Normal Controls
n=5 Participants
Normal controls will have HOMA2 IR of 80%S or greater, normal hormone levels, regular menstrual cycles (range 24 - 34 days), and lack hirsutism and acne. Control subjects are matched for age and education with the PCOS affected women. Control data is measured once (at baseline time frame) for the entire study.
|
|---|---|---|---|
|
Mu-opioid Binding Potential Measured in Left Amygdala
|
2.28 ratio
Standard Deviation .17
|
2.08 ratio
Standard Deviation .19
|
2.03 ratio
Standard Deviation .07
|
PRIMARY outcome
Timeframe: Baseline and 4 monthsMu-opioid binding potential in right amygdala measured before and after 4 months of Metformin treatment. Mu-opioid binding potential is measured in vivo with C11-carfentanil positron emission tomography in women with PCOS before and after 4 months of metformin treatment. Binding Potential is measured by the ratio of Mu-opioid receptor concentration (Bmax)/Receptor radiotracer (C11-carfentanil) affinity (Kd.) Control group was measured at baseline only.
Outcome measures
| Measure |
PCOS Affected Women Pre-Metformin (Baseline)
n=7 Participants
PCOS will be defined as meeting the criteria of irregular menstrual cycles and hyperandrogenism (on physical exam or laboratory testing), with other causes ruled out. Subjects with insulin resistant PCOS must meet criteria for insulin resistance based on the 2 hr OGTT (Oral Glucose Tolerance Test). Insulin resistance will be defined as fasting HOMA2 IR of 60%S or less.
|
PCOS Affected Women Post-Metformin (After 4 Months)
n=7 Participants
PCOS will be defined as meeting the criteria of irregular menstrual cycles and hyperandrogenism (on physical exam or laboratory testing), with other causes ruled out. Subjects with insulin resistant PCOS must meet criteria for insulin resistance based on the 2 hr OGTT (Oral Glucose Tolerance Test). Insulin resistance will be defined as fasting HOMA2 IR of 60%S or less.
|
Normal Controls
n=5 Participants
Normal controls will have HOMA2 IR of 80%S or greater, normal hormone levels, regular menstrual cycles (range 24 - 34 days), and lack hirsutism and acne. Control subjects are matched for age and education with the PCOS affected women. Control data is measured once (at baseline time frame) for the entire study.
|
|---|---|---|---|
|
Mu-opioid Binding Potential Measured in Right Amygdala
|
2.28 ratio
Standard Deviation .23
|
2.11 ratio
Standard Deviation .22
|
2.06 ratio
Standard Deviation .26
|
Adverse Events
Normal Controls
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
PCOS Affected Women on Metformin
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Normal Controls
n=5 participants at risk
Women without PCOS
|
PCOS Affected Women on Metformin
n=7 participants at risk
Women with PCOS and insulin resistance
|
|---|---|---|
|
Metabolism and nutrition disorders
High Glucose During Oral Glucose Tolerance Test (OGTT)
|
0.00%
0/5 • Adverse events were followed in the course of 2 years.
|
14.3%
1/7 • Number of events 1 • Adverse events were followed in the course of 2 years.
|
|
General disorders
Nausea from Carfentanil at PET
|
20.0%
1/5 • Number of events 1 • Adverse events were followed in the course of 2 years.
|
0.00%
0/7 • Adverse events were followed in the course of 2 years.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place