Normal Healthy VolunteersPhase 1NCT02026973
Impact of Endogenous E2 on SSI and GH Rebound
A Phase 1 study testing Fulvestrant, Anastrozole and Somatostatin in people with Normal Healthy Volunteers, run by Mayo Clinic at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 55 to 80 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Normal Healthy Volunteers
- What is being tested?
- Fulvestrant, Anastrozole and Somatostatin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 62 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2014to Nov 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 to 80 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 60 healthy post-menopausal women (ages 55 to 80 y);
- BMI 18-30 kg/m2
- Community dwelling; and voluntarily consenting
Who cannot join
- 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;
Show all 16Show fewer
- 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.
- Pre-menopausal status as determined by screening hormone measurements.
Trial locations and contacts
1 site in 1 country.
United States1 site
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
About this study
Official title: Impact of Endogenous Estrogen on Somatostatin Inhibition and Growth Hormone Rebound in Older Women
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.
Read the detailed 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.
- Conditions
- Normal Healthy Volunteers
- Being tested
- Fulvestrant, Anastrozole, Placebo, Somatostatin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FulvestrantDrug
AnastrozoleDrug
PlaceboDrug
SomatostatinDrug
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Fulvestrant; Drug: Anastrozole; Drug: Somatostatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: 14-18 days: From date of randomization to overnight visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jan 2014 (estimated)
- Study startMar 2014
- Primary completionNov 2015
- Study completionNov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Normal Healthy VolunteersStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Johannes D. Veldhuis, Mayo Clinic
- Investigators
- Johannes Veldhuis, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02026973
- Sponsor's protocol ID
- 13-007623
- Status last verified
- Mar 2016
- First submitted
- 31 Dec 2013
- Last updated
- 16 Mar 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Endogenous Estrogen on Somatostatin Inhibition and Growth Hormone Rebound in Older Women
- ClinicalTrials.gov ID
- NCT02026973
- Acronym / sponsor ID
- 13-007623
- Conditions
- Normal Healthy Volunteers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- Mar 2014
- Primary completion
- Nov 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 3 Jan 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| IM Placebo/Oral Placebo | Experimental | Drug: Placebo, Drug: SomatostatinIM 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. |
| IM Placebo/PO Anastrozole | Experimental | Drug: Anastrozole, Drug: Placebo, Drug: SomatostatinIM 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. |
| IM Fulvestrant/PO Placebo | Experimental | Drug: Fulvestrant, Drug: Placebo, Drug: SomatostatinIM 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. |
| IM Fulvestrant/IM Anastrozole | Experimental | Drug: Fulvestrant, Drug: Anastrozole, Drug: SomatostatinIM 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. |
Who may qualify
- Ages
- 55 to 80 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 60 healthy post-menopausal women (ages 55 to 80 y);
- BMI 18-30 kg/m2
- Community dwelling; and voluntarily consenting
Key exclusion criteria (16 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 |
Primary outcome
The summed mass of GH over 10 hours.
Time frame: 14-18 days: From date of randomization to overnight visit
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.
1 secondary outcome
The summed mass of GH over a 2h Somatostatin infusion and 3h rebound window
Time frame: 14-18 days: From date of randomization to overnight visit
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Mar 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Johannes Veldhuis, MD principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Fulvestrant, Anastrozole and Somatostatin in people with Normal Healthy Volunteers, run by Mayo Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The summed mass of GH over 10 hours. (time frame: 14-18 days: From date of randomization to overnight visit). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2016.