- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02272647
Progesterone Amplifies Estrogen-stimulated Growth Hormone Secretion in Older Women
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The systemic availability and orderly secretion patterns of GH and sex steroids decline in healthy aging men and women. The combined changes have substantial clinical implications to aging-related physical frailty, diminished aerobic capacity, sarcopenia, osteopenia, visceral adiposity, glucose intolerance, and reduced psychosocial wellbeing. Whereas androgen is considered the main trophic (anabolic) sex steroid, recent data demonstrate that certain tissues respond principally to GH and testosterone-derived estradiol, Estrogen (E2) (e.g. bone, brain, liver and pituitary). In principle, frailty may thus be associated with dual GH and sex-steroid deficiencies. Additionally, young, but not older healthy women secrete significant amounts of progesterone for approximately 14 days during the luteal phase of every menstrual cycle. When GH levels rise nearly two fold, the investigators hypothesize that progesterone potentiates the GH response to E2. This hypothesis arises from scattered indirect studies often using synthetic progestins with partial androgen agonism, instead of progesterone per se.
Because there is no basis for estimating statistical power for this novel paradigm, 40 women, 10 each in 4 groups, will be studied. The pilot data will be used to calculate statistical power for a definitive R01-based investigation of gender-specific distinctions in estrogen-regulated pituitary-hormone secretion.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Minnesota
-
Rochester, Minnesota, United States, 55905
- Mayo Clinic in Rochester
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- women ages 50 to 80
postmenopausal as defined by: any combination of the following
- Hormonally postmenopausal for 1 year
- Lh greater than 15 IU/L, FSH greater than 30 IU/L
- Total hysterectomy with oophorectomy greater than one year
- Hysterectomy with ovaries preserved with hormone levels: Lh > 15 IU/L, FSH > 30 IU/L
- Following laboratory results with normal range, unless PI approves out of range values.
- BMI 18 to 35
Exclusion Criteria:
- structural hypothalamo-pituitary-gonadal disease
- endocrinopathy (diseases involving the following organs pituitary, thyroid, adrenals, ovaries, testes and pancreas), other than primary thyroid failure receiving replacement
- recent (within 2 weeks) estrogen, progestin, anabolic steroid or glucocorticoid use
- clinically significant ECG abnormality as determined by study team physicians
- obstructive uropathy
- history of a stroke
- history of MI or angina
- acute or chronic systemic disease
- recent transmeridian travel (traversing more than 3 time zones within 7 days of admission)
- current night shift work
- concurrent use of neuropsychiatric medications
- alcohol or drug abuse, current and within 2 years
- history of depression, psychosis, or mania
- weight gain or loss (2 kg or more in 3 weeks)
- BMI > 35 kg/m2
- anemia, hemoglobin less than 12.5 g/dl
- abnormal hepatorenal function, creatinine outside normal range, ALT greater than two times normal range
- biochemical and chemistry lab results out of physician acceptable range
- history of deep-vein thrombophlebitis
- history of Congestive Heart Failure, cardiac arrhythmias, and medications used to treat cardiac arrhythmias
- known allergy to estradiol valerate, castor oil or sesame oil
- history of smoking within the last 2 years
- untreated gall bladder disease
- lack of voluntary, written informed consent
- history of carcinoma excluding localized basal cell or squamous cell, including women with known, suspected or history of breast cancer
- not clinically postmenopausal
- women with allergies to nuts will not be enrolled in the study.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: BASIC_SCIENCE
- Allocation: RANDOMIZED
- Interventional Model: CROSSOVER
- Masking: SINGLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: IM Plac - Oral Plac - Ghrelin
Day 1: IM Saline Placebo (0.25 ml) Day 10: IM Saline Placebo (0.5 ml) and Oral Placebo 3x/day Day 23: IV push of ghrelin (0.3 ug/kg) + Placebo (for 10 days)
|
(in lieu of Medroxyprogesterone)
|
EXPERIMENTAL: IM Plac - Oral Prog - Ghrelin
Day 1: IM Saline Placebo (0.25 ml) Day 10: IM Saline Placebo (0.5 ml) and Oral Micronized Progesterone 3x/day Day 23: IV push of ghrelin (0.3 ug/kg) + Placebo (for 10 days)
|
(in lieu of Medroxyprogesterone)
|
EXPERIMENTAL: IM E2 - Oral Plac - Ghrelin
Day 1: IM Estradiol (2.5 mg) Day 10: IM Estradiol (5.0 mg) and Oral Placebo 3x/day Day 23: IV push of ghrelin (0.3 ug/kg) + Medroxyprogesterone (5 mg - for 10 days)
|
(in lieu of Medroxyprogesterone)
|
EXPERIMENTAL: IM E2 - Oral Prog - Ghrelin
Day 1: IM Estradiol (2.5 mg) Day 10: IM Estradiol (5.0 mg) and Oral Micronized Progesterone 3x/day Day 23: IV push of ghrelin (0.3 ug/kg) + Placebo (for 10 days)
|
(in lieu of Medroxyprogesterone)
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Logarithm of the ratio of the normalized growth hormone secretion rate over the first 10 hr.
Time Frame: The subject will be followed on average for a month. Growth hormone measurements will occur on Day 23 after initiation of study drug administration
|
Subjects will be given IM placebo/estradiol on Day 1. 10 days later they will receive IM placebo/estradiol again, then start progesterone/placebo capsules for 14 days.
On Day 23, subjects will undergo a 12-h overnight (2200 - 1000h) fasting, 10-min blood sampling.
The primary comparison parameter is the logarithm of the ratio of the normalized growth hormone secretion rate over the first 10 hr.
|
The subject will be followed on average for a month. Growth hormone measurements will occur on Day 23 after initiation of study drug administration
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Growth hormone secretion post ghrelin injection
Time Frame: The subject will be followed on average for a month. Growth hormone measurements will occur on Day 23 after initiation of study drug administration
|
Subjects will be given IM placebo/estradiol on Day 1. 10 days later they will receive IM placebo/estradiol again, then start progesterone/placebo capsules for 14 days.
On Day 23, subjects will undergo a 12-h overnight (2200 - 1000h) fasting, 10-min blood sampling.
A secondary outcome is GH secretion over the 2 hr after bolus ghrelin injection, a potent growth hormone secretagogue
|
The subject will be followed on average for a month. Growth hormone measurements will occur on Day 23 after initiation of study drug administration
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Antineoplastic Agents
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Estrogens
- Contraceptive Agents, Hormonal
- Contraceptive Agents
- Reproductive Control Agents
- Contraceptives, Oral
- Contraceptive Agents, Female
- Contraceptives, Oral, Synthetic
- Contraceptives, Oral, Hormonal
- Progestins
- Contraceptive Agents, Male
- Estradiol
- Progesterone
- Estradiol 17 beta-cypionate
- Estradiol 3-benzoate
- Polyestradiol phosphate
- Medroxyprogesterone Acetate
- Medroxyprogesterone
Other Study ID Numbers
- 14-002829
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.
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