Trial · Interventional
Active, not recruitingNot applicableResults postedRegistry dataUnited States
1 trial · 1 ongoing · 1 with posted results
Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.
Obesity plays an adverse role at every stage of conception and pregnancy and mounting evidence implicates relative hypogonadotropic hypogonadism, and reduced menstrual cycle hormone secretion as likely contributors to the subfertility phenotype and possible contributors to complications of pregnancy and the developmental origin of adult diseases such as diabetes and cardiovascular disease. This study will be the first comprehensive investigation to tie together the patterns of hyperinsulinemia, hyperlipidemia and inflammation, characteristic of obesity and obesity-caused relative hypogonadotropic hypogonadotropism and its potential adverse reproductive outcomes. The investigators findings will be used to inform a subsequent clinical intervention to optimize reproductive outcomes for obese women and their offspring.
Active comparator
Aim 1-Administration of FFA in an acute model
Reproduction of the reproductive phenotype of obesity in Normal Weight Women (NWW) by: 1\) infusing insulin and free fatty acids (FFAs) in short term experiments and measuring gonadotropin pulsatility and pituitary GnRH response Assessment of the gluco-regulatory and anti-lipolytic actions of insulin with a 2-stage, Hyperinsulinemic, Euglycemic Clamp (HEC) to evaluate both suppression of lipolysis and hepatic glucose production.
Experimental
Aim 2-Hyperinsulinemic Euglycemic Clamp after a chronic administration of a diet
Assessment of the gluco-regulatory and anti-lipolytic actions of insulin with a 2-stage, Hyperinsulinemic, Euglycemic Clamp (HEC) to evaluate both suppression of lipolysis and hepatic glucose production. Inducing a chronic model of the reprometabolic syndrome by administering a eucaloric diet that is relatively high in pro-inflammatory omega-6 fatty acids and low in anti-inflammatory omega-3 fatty acids (high fat diet; HFD) for one month while monitoring gonadotropin pulsatility and daily urinary reproductive hormone excretion.
Outcomes the sponsor listed as primary.
Change in LH Pulse Amplitude Before and After Acute or Chronic FFA Administration
Time frame · First 4 hours of the frequent blood sampling study before and after FFA administration
LH-Luteinizing Hormone Pulse Amplitude before and after administration of FFAs. This is a measure of the post supplementation frequent blood sampling session and the baseline session.
Change in Steady State Amount of Glucose Metabolized at the Set Insulin Infusion Rate Under Euglycemic Conditions
Time frame · 30 minutes
Primary outcome will be M, which represents the steady state amount of glucose metabolized at the set insulin infusion rate under euglycemic conditions, which is equal to the glucose infused when the participant is euglycemic during the second stage of the HEC49. The final 30 minutes of the clamp period will be considered steady state. Glucose concentrations will be determined with the glucose oxidase method (Beckman Glucose Analyzer 2; Beckman Instruments, Fullerton, CA), while ELISA methods will be used for insulin measurements (Alpco, Salem, NH).
Change in GnRH Response Before and After Acute or Chronic FFA Administration
Time frame · After the administration of GnRH at each FSS before and after acute and chronic FFA administration was assessed for up to 4 hours.
GnRH response will be compared between the non-intervention and intervention study as described above for gonadotropin pulsatility. The Investigator have used area under the curve methods to determine the LH response to exogenous GnRH and will utilize the same methodology as the investigator have done in the past.
Change in Mean FSH Parameter Before and After Acute or Chronic FFA Administration
Time frame · Before and after FFA adminstration
FSH parameters will be compared between the non-intervention and intervention studies for both aims as described above for gonadotropin pulsatility. The investigator will compare mean FSH, as pulsatility of FSH is less obvious than LH.
Changes in Gonadotropin Pulse Frequency
Time frame · 4 hours
The investigator will compare changes in gonadotropin pulse frequency (for LH, and if we can detect distinct FSH pulses, we will compare FSH as well), mean LH and FSH and kinetics of LH, and if possible, FSH, before and after the intervention, as previously reported
Urinary Hormone Profiles Before, During and After High Fat Diet Administration.
Time frame · Urinary assays will be measured for 4 menstrual cycles (approximately 4 months or 115 days)
Urinary hormone profiles will be assessed for the entire cycle before and two cycles after initiation of the HFD using previously described menstrual cycle parameters suitable for urinary hormone determinations. The LH peak will be determined for all cycles that demonstrate a Progesterone increment consistent with ovulation. Follicular and luteal phase lengths will be calculated, as will integrated follicular, luteal and whole cycle LH, FSH, E1c and Progesterone. The measurement is the change in value from baseline to 4 menstrual cycles (approximately 4 months) after baseline.
Glucose Measurements Before and After FFA Administration.
Time frame · 60 Minutes during HEC
Glucose will be measured by the CTRC laboratories before and after FFA administration..
Comparison of RBC Lipids Before and After the FFA Administration
Time frame · 30 Minutes during the HEC
RBC lipids will also be compared, as the investigator predict that the HFD will result in increased omega-6 rich FFAs and less omega-3 FFAs
DEXA Body Composition Comparison
Time frame · 5 months-before and after the interventation.
DEXA body composition will be measured before and after the intervention.
Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.
| Group | Value (IU/L) | Spread |
|---|---|---|
| Aim 1-Supplementation of FFAs in an Acute or Chronic Model. | 2.33 | 1.21 |
| Aim 2-Hyperinsulinemic Euglycemic Clamp. | 2.4 | 1.1 |
| Group | Value (mg/dL) | Spread |
|---|---|---|
| Aim 1-Acute and Chronic Administration of FFAs. | 1.98 | 0.14 |
| Aim 2-Hyperinsulinemic Euglycemic Clamp | 0.0485 | 0.0641 |
| Group | Value (IU/L*min) | Spread |
|---|---|---|
| Aim 1-Administration of FFA in an Acute Model | 567.63 | 1.22 |
| Aim 2-Hyperinsulinemic Euglycemic Clamp After a Chronic Administration of a Diet | 355.12 | 1.23 |
| Group | Value (IU/L*min) | Spread |
|---|---|---|
| Aim 1-Supplementation of FFAs in an Acute or Chronic Model. | 242.46 | 1.23 |
| Aim 2-Hyperinsulinemic Euglycemic Clamp. | 158.99 | 1.25 |
| Group | Value (IU/L) | Spread |
|---|---|---|
| Aim 1-Supplementation of FFAs in an Acute or Chronic Model. | 2.33 | 1.21 |
| Aim 2-Hyperinsulinemic Euglycemic Clamp. | 1.49 | 1.23 |
| Group | Value (mIU/mg Creatinine) | Spread |
|---|---|---|
| Chronic Model | -10.71 | 2.2 |
| Group | Value |
|---|
| Group | Value |
|---|
| Group | Deaths | Serious events | Other events |
|---|---|---|---|
| Aim 1Reproduction of the reproductive phenotype of obesity in Normal Weight Women (NWW) by: 1. infusing insulin and free fatty acids (FFAs) in short term experiments and measuring gonadotropin pulsatility and pituitary GnRH response; and 2. inducing a chronic model of the reprometabolic syndrome by administering a eucaloric diet that is relatively high in pro-inflammatory omega-6 fatty acids and low in anti-inflammatory omega-3 fatty acids (high fat diet; HFD) for one month while monitoring gonadotropin pulsatility and daily urinary reproductive hormone excretion. Insulin Intralipid Dextrose Heparin GnRH | 0 / 13 | 0 / 13 | 1 / 13 |
| Aim 2Assessment of the gluco-regulatory and anti-lipolytic actions of insulin with a 2-stage, Hyperinsulinemic, Euglycemic Clamp (HEC) to evaluate both suppression of lipolysis and hepatic glucose production. Insulin Intralipid Dextrose Heparin GnRH Hyperinsulinemic Euglycemic Clamp | 0 / 18 | 0 / 18 | 0 / 18 |
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