Impact of Endogenous E2 on SSI and GH Rebound

Normal Healthy Volunteers Clinical Trial

Official title:

Impact of Endogenous Estrogen on Somatostatin Inhibition and Growth Hormone Rebound in Older Women

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02026973
• Other study ID #: 13-007623
• Status: Completed
• Phase: Phase 1
• First received: December 31, 2013
• Last updated: March 14, 2016
• Start date: March 2014
• Est. completion date: November 2015

Study information

• Verified date: March 2016
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Endogenous estrogens maintain growth hormone (GH) secretion in postmenopausal women by potentiating endogenous GH-releasing hormone (GHRH) drive and restraining somatostatin inhibition of GH release.

Description:

Systemic concentrations of testosterone (Te), estradiol (E2), GH, IGF-I and IGFBP-3 decline in healthy aging individuals (1-3). Sex-steroid deprivation accentuates GH and IGF-I depletion, since Te and E2 stimulate GH and IGF-I production in older adults, hypogonadal patients of all ages, and patients undergoing gender reassignment (1,2,4). Tamoxifen blocks the effect of Te, suggesting involvement of E2 in GH's stimulation in men (5). E2 also stimulates GH secretion in women, putatively via the nuclear estrogen receptor (ER-alpha) (1,2,6,7). Because Te, E2 and GH fall with menopause, and Te is converted to E2 by aromatization in the body (8-10), we postulate that diminished Te concentrations, Te→E2 concentrations and low E2 mediate low GH output in older women. What remains unknown is whether the low E2 levels in postmenopausal women retain GH-stimulating effects. To test this notion would require blocking: (i) aromatase-enzyme activity, which mediates E2 synthesis from Te, and/or (ii) estrogen receptor-alpha, which transduces most of E2's stimulation of the GH axis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: November 2015
• Est. primary completion date: November 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 55 Years to 80 Years

Eligibility

Inclusion:

1. 60 healthy post-menopausal women (ages 55 to 80 y);

2. BMI 18-30 kg/m2

3. Community dwelling; and voluntarily consenting

Exclusion:

1. Recent use of psychotropic or neuroactive drugs (within five biological half-lives);

2. Obesity (outside weight range above);

3. Laboratory test results not deemed physician acceptable, cholesterol >250, triglycerides > 300, BUN >30 or creatinine > 1.5 mg/dL, liver function tests exceeding twice upper limit of normal, electrolyte abnormality, anemia;

4. Drug or alcohol abuse, psychosis, depression, mania or severe anxiety;

5. Systemic inflammatory disease;

6. Endocrinopathy, other than primary thyroidal failure receiving replacement;

7. Nightshift work or recent transmeridian travel (exceeding 3 time zones within 7 days of CRU admission);

8. Acute weight change (loss or gain of > 2 kg in 6 weeks);

9. Systemic illness

10. Unwillingness to provide written informed consent.

11. Allergy to anastrozole or fulvestrant (treatment drugs).

12. History or suspicion of breast cancer.

13. History of carcinoma (excluding localized basal cell carcinoma removed or surgically treated with no recurrence).

14. History of thrombotic arterial disease (stroke, TIA, MI, angina) or deep-vein thrombophlebitis.

15. History of CHF, cardiac arrhythmias, congenital QT prolongation, and medications used to treat cardiac arrhythmias.

16. Pre-menopausal status as determined by screening hormone measurements.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Normal Healthy Volunteers

Intervention

Drug:
• Fulvestrant

• Anastrozole

• Placebo

• Somatostatin

Locations

Country	Name	City	State
United States	Mayo Clinic in Rochester	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Mayo Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The summed mass of GH over 10 hours.	Subjects will be given placebo/fulvestrant and placebo/anastrozole on Day 1 to take for 14-18 days. For one night between Days 14-18, from date of randomization, subjects will undergo a 15-h overnight (2200-1300h) fasting, 10-min blood sampling. The primary analytical outcome is the summed mass of GH secreted in pulses over the first 10h of overnight blood samples. Pulsatile GH is relevant, since sex-steroid hormones and regulatory peptides uniquely control GH secretory-burst mass.	14-18 days: From date of randomization to overnight visit	Yes
Secondary	The summed mass of GH over a 2h Somatostatin infusion and 3h rebound window	Subjects will be given placebo/fulvestrant and placebo/anastrozole on Day 1 to take for 14-18 days. For one night between Days 14-18, from date of randomization, subjects will undergo a 15-h overnight (2200-1300h) fasting, 10-min blood sampling. The secondary outcome is summed GH secretory-burst-mass values during the overnight visit, specifically: a 2-h somatostatin infusion and subsequent 3-h rebound window.	14-18 days: From date of randomization to overnight visit	Yes