Regulation of Cortisol Metabolism and Fat Patterning

Sponsor

Oregon Health and Science University (Other)

Overall Status

Unknown status

CT.gov ID

NCT00694733

Collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)

140

Enrollment

Location

Arms

184

Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if estrogen or testosterone can affect cortisol levels and where fat builds up in our bodies.

Condition or Disease	Intervention/Treatment	Phase
Obesity Menopausal Syndrome	Drug: Placebo injection Drug: Depo Lupron/Aromatase inhibitor Drug: Depo Lupron/placebo Drug: placebo Drug: Estrogen cream	N/A

Detailed Description

Subjects will be studied 3 or 4 times on the inpatient unit of the Oregon Clinical and Translational Research Center. During each visit, testing will include measuring the amount of whole body fat and fat in the stomach area, muscle, and liver; levels of cortisol in the blood, urine, and fat tissue (taken from a biopsy); how well insulin works (insulin sensitivity).

Study Design

Study Type:

Interventional

Actual Enrollment :

140 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Basic Science

Official Title:

Regulation of Cortisol Metabolism and Fat Patterning

Study Start Date :

May 1, 2005

Anticipated Primary Completion Date :

Mar 1, 2020

Anticipated Study Completion Date :

Sep 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: 1 Men on placebo injections for 4 months	Drug: Placebo injection Normal saline injection IM monthly for 4 months Other Names: Normal Saline
Active Comparator: 2 Men who receive Depo Lupron for 4 months, then are replaced with testosterone and aromatase inhibitor for 4 months.	Drug: Depo Lupron/Aromatase inhibitor Depo Lupron injection 7.5mg IM monthly for 8 months, with addition of testosterone gel and aromatase inhibitor months 4-8. Other Names: Depo-Lupron Testim 1% gel Anastrozole Arimidex
Active Comparator: 3 Men who receive Depo Lupron for 4 months, then are replaced with testosterone and placebo for 4 months.	Drug: Depo Lupron/placebo Depo Lupron injection 7.5mg IM monthly for 8 months, with addition of testosterone gel and placebo months 4-8. Other Names: Depo-Lupron Testim 1% gel Placebo capsules
Placebo Comparator: 4 Women on placebo cream	Drug: placebo Placebo Cream 1ml applied twice daily for four months Other Names: Placebo cream
Active Comparator: 5 Women on estrogen cream	Drug: Estrogen cream Estrogen cream 1 ml twice daily, dose titrated to maintain estradiol level between 60 and 280 pg/ml. Other Names: Estradiol cream

Outcome Measures

Primary Outcome Measures

To measure 24-hour CPR, free cortisol, and cortisol binding globulin levels in plasma; HSD 1 activity, glucocorticoid receptor binding, and cortisol levels in adipocytes; and urinary excretion of cortisol, cortisone and their metabolites. [Before and after hormone replacement therapy]

Secondary Outcome Measures

To measure intramyocellular fat and intrahepatic fat by MRS, visceral and subcutaneous abdominal fat by CT scan, body composition (fat mass, lean mass, and bone mass) by DXA, and insulin sensitivity. [Before and after hormone replacement therapy]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 62 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

40 postmenopausal women (age 40-62) and 30 men (age 18-45) will be recruited if they are healthy, at their lifetime maximal weight, have been weight stable for at least six months prior to entry, have a BMI between 19 and 39.9 kg/m2, and be willing to commit to not making significant changes to their diet or daily activities while enrolled in the study.

Exclusion Criteria:

Subjects will be excluded for potential confounders on body weight, cortisol production rates, sex steroid metabolism, or contraindications to strong magnetic fields:

Age less than 18 to exclude those who might be experiencing alterations in cortisol production or weight as a result of adolescent growth
Subjects who exercise > 30 minutes/day, 3 times a week
Smokers
Heavy alcohol drinkers (> 2 drinks/ day)
Subjects with medical diagnosis including diabetes, heart disease, and cancer
Subjects with psychiatric illness (i.e., depression, psychosis, bipolar, schizophrenia; or are taking medications for these disorders)
BMI 40 kg/m2, since obesity influences levels of sex steroids and sex hormone binding globulin; or body weight > 136 kg (300 lbs), since this is the weight limit for the DEXA and MR machines
Presence of metal in the body such as body piercing, shrapnel, cardiac pacemakers or aneurysm clips
Endocrine diseases affecting body composition, such as untreated hypothyroidism or Cushing's syndrome, will be excluded by history and physical examination, or by laboratory evaluation if necessary.

Women with a contraindication to estrogen use will also be excluded, including: an estrogen dependent malignancy, active thrombophlebitis, history of deep venous thrombosis, hypertriglyceridemia, untreated hypertension, cardiovascular disease, migraine headaches, or current tobacco use.
Women with frequent hot flashes or disrupted sleep will also be excluded since they will be unlikely to tolerate randomization to placebo and continued symptoms and altered sleep cycles will independently affect cortisol secretion patterns.
All volunteers will have had a normal mammogram within the previous 12 months.
Any subject with previously unevaluated postmenopausal bleeding will not be included and, instead, will be referred to a physician for evaluation.
Women who underwent surgical menopause (bilateral ovariectomy) must be at least one year out from their surgery before considered eligible so as to allow weight stabilization after the procedure.
Men will have had a prostate exam by their primary health provider within the previous year or by the PI at the time of screening for this study.
Any subjects taking a blood thinning medication or with an abnormal exam will not be included and, instead, will be referred to a physician for evaluation