Impact of Endogenous E2 on SSI and GH Rebound

NCT02026973 | Completed Phase 1

• 1 other identifier: 13-007623
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Normal Healthy Volunteers

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• The summed mass of GH over a 2h Somatostatin infusion and 3h rebound window

  14-18 days: From date of randomization to overnight visit

Study Arms (4)

IM Placebo/Oral Placebo

EXPERIMENTAL

IM placebo given once on Day 1; Oral placebo pills daily x14-18 days. Somatostatin 1mcg/kg/hr will be administered for 2 hours from 8-10AM on the overnight visit.

Drug: Placebo; Drug: Somatostatin

IM Placebo/PO Anastrozole

EXPERIMENTAL

IM placebo given once on Day 1; Oral Anastrozole 2.0mg pills daily x14-18 days. Somatostatin 1mcg/kg/hr will be administered for 2 hours from 8-10AM on the overnight visit.

Drug: Anastrozole; Drug: Placebo; Drug: Somatostatin

IM Fulvestrant/PO Placebo

EXPERIMENTAL

IM Fulvestrant 250mg given once on Day 1; Oral Placebo pills daily x14-18 days. Somatostatin 1mcg/kg/hr will be administered for 2 hours from 8-10AM on the overnight visit.

Drug: Fulvestrant; Drug: Placebo; Drug: Somatostatin

IM Fulvestrant/IM Anastrozole

EXPERIMENTAL

IM Fulvestrant 250mg given once on Day 1; Oral Anastrozole pills daily x14-18 days. Somatostatin 1mcg/kg/hr will be administered for 2 hours from 8-10AM on the overnight visit.

Drug: Fulvestrant; Drug: Anastrozole; Drug: Somatostatin

Interventions

Fulvestrant DRUG

IM Fulvestrant/IM Anastrozole; IM Fulvestrant/PO Placebo

Anastrozole DRUG

IM Fulvestrant/IM Anastrozole; IM Placebo/PO Anastrozole

Placebo DRUG

IM Fulvestrant/PO Placebo; IM Placebo/Oral Placebo; IM Placebo/PO Anastrozole

Somatostatin DRUG

IM Fulvestrant/IM Anastrozole; IM Fulvestrant/PO Placebo; IM Placebo/Oral Placebo; IM Placebo/PO Anastrozole

Eligibility Criteria

• Age: 55 Years - 80 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• healthy post-menopausal women (ages 55 to 80 y);
• BMI 18-30 kg/m2
• Community dwelling; and voluntarily consenting

You may not qualify if:

• Recent use of psychotropic or neuroactive drugs (within five biological half-lives);
• Obesity (outside weight range above);
• 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;
• Drug or alcohol abuse, psychosis, depression, mania or severe anxiety;
• Systemic inflammatory disease;
• Endocrinopathy, other than primary thyroidal failure receiving replacement;
• Nightshift work or recent transmeridian travel (exceeding 3 time zones within 7 days of CRU admission);
• Acute weight change (loss or gain of \> 2 kg in 6 weeks);
• Systemic illness
• Unwillingness to provide written informed consent.
• Allergy to anastrozole or fulvestrant (treatment drugs).
• History or suspicion of breast cancer.
• History of carcinoma (excluding localized basal cell carcinoma removed or surgically treated with no recurrence).
• History of thrombotic arterial disease (stroke, TIA, MI, angina) or deep-vein thrombophlebitis.
• History of CHF, cardiac arrhythmias, congenital QT prolongation, and medications used to treat cardiac arrhythmias.

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Interventions

Fulvestrant; Anastrozole; Somatostatin

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pituitary Hormone Release Inhibiting Hormones; Hypothalamic Hormones; Peptide Hormones; Pancreatic Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Nerve Tissue Proteins; Proteins

Study Officials

• Johannes Veldhuis, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 31, 2013
• First Posted: January 3, 2014
• Study Start: March 1, 2014
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: March 16, 2016

Record last verified: 2016-03

Locations

US (1)