- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02653092
Reprometabolic Syndrome Mediates Subfertility in Obesity
Study Overview
Status
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Colorado
-
Aurora, Colorado, United States, 80045
- University of Colorado Denver
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Body Mass Index (BMI) at least 18 but less than 25 kg/m2
- No history of chronic disease affecting hormone production, metabolism, or clearance
- No use of medications known to alter or interact with reproductive hormones or insulin metabolism (e.g. thiazolidinediones, metformin)
- No use of reproductive hormones within 3 months of enrollment
- Normal prolactin and thyroid stimulating hormone levels at screening
- History of regular menstrual cycles every 25-35 days
- Use of a reliable method of contraception (female or male partner sterilization; intra uterine device (IUD); abstinence; diaphragm)
- Normal hemoglobin A1c
- Screening hemoglobin >11gm/dl
Exclusion Criteria:
- Women with a baseline dietary assessment indicative of >35% daily calorie consumption from fat (as calculated based upon initial screening survey) will be excluded, as the impact of increasing their dietary fat intake may be minimal.
- Women with fasting triglycerides >300mg/dl at screening will be excluded, as they might be at risk for acute elevation of triglycerides and even pancreatitis if placed on a high fat diet
- Inability to comply with the protocol. Individuals who travel frequently, or who eat most of their meals outside of their home will be excluded, as it will be difficult to impossible for them to comply with the diet, to pick up the food cartons, etc.
- Because high proportions of dairy fat will be needed to attain 48% calories from fat in the diet, vegans and lactose intolerant individuals will be excluded.
- Pregnant women or women planning to become pregnant will be excluded.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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. |
Other Names:
Other Names:
Other Names:
Other Names:
Other Names:
|
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. |
Other Names:
Other Names:
Other Names:
Other Names:
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
First 4 hours of the frequent blood sampling study before and after FFA administration
|
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).
|
30 minutes
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
4 hours
|
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.
|
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.
|
After the administration of GnRH at each FSS before and after acute and chronic FFA administration.
|
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.
|
Before and after FFA adminstration
|
Urinary Hormone Profiles Before, During and After FFA Administration.
Time Frame: Urinary assays will be measured before, during and after FFA administration.
|
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 determinations42.
The presumptive day of ovulation, called the Day of Luteal Transition (DLT) will be determined for all cycles that demonstrate a Prostaglandin increment consistent with ovulation.
Follicular and luteal phase lengths will be calculated, as will integrated follicular, luteal and whole cycle LH, FSH, E1c and Prostaglandin.
Cycle parameters will be compared using a repeated measures mixed ANOVA, if data are normally distributed or can be transformed to fit a normal distribution, or appropriate non-parametric testing as needed.
Statistical adjustment will be made for multiple comparisons of potentially covarying hormones.
|
Urinary assays will be measured before, during and after FFA administration.
|
Insulin Suppression of Lipolysis Before and After FFA Administration.
Time Frame: 30 Minutes- during HEC
|
Insulin suppression of lipolysis.
The Investigator will assess whether the HFD exposure results in the expected compromise of insulin action at the low-dose (4 mU/m2/min) stage of the HEC.
Plasma glycerol will be measured by the CTRC Colorado Clinical Nutrition Research Unit Mass Spectrometry Core Laboratory.
The Glycerol rate of appearance (GlycRA) will be determined over the last 30 minutes of the low dose (4 mU/m2/min ) and high dose (40 mU/m2/min) clamp using the non-steady-state equation of Steele.
|
30 Minutes- during HEC
|
Insulin Measurements Before and After FFA Administration.
Time Frame: 60 Minutes during HEC
|
Insulin will be measured by the CTRC laboratories.
|
60 Minutes during HEC
|
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..
|
60 Minutes during HEC
|
FFAs Measurements During the HEC
Time Frame: 60 Minutes during the HEC
|
FFAs will be measured by the CTRC laboratories.
Plasma non-esterified FFAs will be measured after lipid extraction of plasma (Wako Diagnostics, Richmond, VA).
Lipids are measured by enzymatic methods (Quest Diagnostics- Nichols Institute, Chantilly, VA)
|
60 Minutes during the HEC
|
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
|
30 Minutes during the HEC
|
DEXA Body Composition Comparison
Time Frame: 5 months-before and after the interventation.
|
DEXA body composition will be measured before and after the intervention.
|
5 months-before and after the interventation.
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Nanette Santoro, MD, University of Colorado, Denver
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Glucose Metabolism Disorders
- Metabolic Diseases
- Endocrine System Diseases
- Gonadal Disorders
- Overnutrition
- Nutrition Disorders
- Overweight
- Body Weight
- Urogenital Diseases
- Genital Diseases
- Obesity
- Infertility
- Hyperinsulinism
- Hypogonadism
- Molecular Mechanisms of Pharmacological Action
- Fibrinolytic Agents
- Fibrin Modulating Agents
- Pharmaceutical Solutions
- Parenteral Nutrition Solutions
- Fat Emulsions, Intravenous
- Heparin
- Soybean oil, phospholipid emulsion
- Anticoagulants
Other Study ID Numbers
- 15-1052
- UL1TR001082 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Obesity
-
Central Hospital, Nancy, FranceNot yet recruiting
-
University of MinnesotaNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)Active, not recruitingAdolescent ObesityUnited States
-
Helsinki University Central HospitalKarolinska Institutet; Folkhälsan Researech CenterEnrolling by invitation
-
Istanbul Medipol University HospitalMedipol UniversityCompletedObesity, Morbid | Obesity, Adolescent | Obesity, Abdominal | Weight, Body | Obesity, VisceralTurkey
-
Queen Fabiola Children's University HospitalNot yet recruitingMorbid Obesity | Adolescent Obesity | Bariatric SurgeryBelgium
-
Azienda Ospedaliero-Universitaria Consorziale Policlinico...Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies; Istituti... and other collaboratorsCompletedMorbid Obesity | Metabolically Healthy ObesityItaly
-
Washington University School of MedicinePatient-Centered Outcomes Research Institute; Pennington Biomedical Research... and other collaboratorsActive, not recruitingOvernutrition | Nutrition Disorders | Overweight | Body Weight | Pediatric Obesity | Body Weight Changes | Childhood Obesity | Weight Gain | Adolescent Obesity | Obesity, Childhood | Overweight and Obesity | Overweight or Obesity | Overweight AdolescentsUnited States
-
The Hospital for Sick ChildrenCompleted
-
Ihuoma EneliCompletedObesity, ChildhoodUnited States
-
Fundació Sant Joan de DéuRecruitingObesity, Childhood | Obesity, AdolescentSpain
Clinical Trials on Insulin
-
Munich Municipal HospitalNovo Nordisk A/SUnknownType 2 Diabetes MellitusGermany
-
Novo Nordisk A/SCompletedDiabetes | Diabetes Mellitus, Type 1Germany
-
Novo Nordisk A/SCompletedDiabetes | Diabetes Mellitus, Type 1United States, Poland, Puerto Rico, Russian Federation, United Kingdom, Denmark, France, Israel, Australia, Romania
-
Novo Nordisk A/SCompletedDiabetes | Diabetes Mellitus, Type 1United States, India, Russian Federation, Belgium, Spain, Israel, Croatia, Serbia, North Macedonia, South Africa, Slovenia, Brazil, Poland, Canada, Czechia
-
Novo Nordisk A/SCompletedDiabetes | Diabetes Mellitus, Type 1Croatia, Italy, Slovakia, Denmark, Macedonia, The Former Yugoslav Republic of, Norway, Russian Federation, Finland, France, Poland, Greece, Romania, Sweden, Czech Republic, Argentina
-
Novo Nordisk A/SCompletedDiabetes Mellitus, Type 2 | DiabetesUnited States, France, Austria, Norway, Algeria
-
Novo Nordisk A/STerminatedDiabetes | Diabetes Mellitus, Type 1United Kingdom
-
Novo Nordisk A/SCompletedDiabetes | Diabetes Mellitus, Type 1Germany
-
Novo Nordisk A/SCompletedDiabetes | Diabetes Mellitus, Type 1Germany, United Kingdom
-
Novo Nordisk A/SCompletedDiabetes Mellitus, Type 2 | DiabetesUnited States, Croatia, India, Israel, Russian Federation, Slovakia, Canada, Serbia, United Kingdom, Puerto Rico