Normal Healthy VolunteersPhase 1NCT02271282
Estradiol-Receptor Blockade in Older Men and Women
A Phase 1 study testing Toremifene and GHRH/Ghrelin combined Injection in people with Normal Healthy Volunteers, run by Mayo Clinic at 1 site in United States.
Trial summary
Repletion of testosterone (Te) in older men drives GH secretion after its aromatization to estradiol (E2), which acts via the estrogen receptor (ER). Conversely, we postulate that estrogen deprivation in postmenopausal women attenuates growth hormone (GH) secretion and insulin-like growth factor-1 (IGF-I) production… Read more about this study
- Who is it for?
- Ages 50 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Normal Healthy Volunteers
- What is being tested?
- Toremifene and GHRH/Ghrelin combined Injection
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2014to May 2016
- 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 50 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 40 healthy women and men (ages 50 to 80 y); women will be post-menopausal (clinically defined by E2 < 50 pg/mL, FSH > 30Iu/L)
- BMI 18-35 kg/m2
- community dwelling; and voluntarily consenting
Who cannot join
- recent use of psychotropic or neuroactive drugs (within five biological half-live);
- obesity (outside weight range above);
- Laboratory test results not deemed physician acceptable, viz potassium <3.5 mEq/L, magnesium <1.5 mEq/L, triglycerides > 300, BUN >30 or creatinine > 1.5 mg/dL, liver functions tests twice upper limit of normal, anemia (hemoglobin must meet Blood Bank requirements - Hgb ≥ 12.5 g/dL)
- drug or alcohol abuse, psychosis, depression, mania or severe anxiety;
- acute or chronic organ-system disease, including renal failure (creatinine > 1.5 mg/dL)
- endocrinopathy, other than primary thyroidal failure receiving replacement
Show all 15Show fewer
- nightshift work or recent transmeridian travel (exceeding 3 time zones within 7 days of admission),
- acute weight change (loss or gain of > 2 kg in 6 weeks);
- allergy to toremifene
- unwillingness to provide written informed consent.
- PSA > 4.0 ng/mL in men
- History or suspicion of prostatic disease (elevated PSA, indeterminate nodule or mass, obstructive uropathy, or breast cancer),
- Other 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 or other strong CYP3A4 inhibitors.
Trial locations and contacts
1 site in 1 country.
United States1 site
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
About this study
Official title: Pilot Study of Estradiol-Receptor Blockade in Older Men and Women
Repletion of testosterone (Te) in older men drives GH secretion after its aromatization to estradiol (E2), which acts via the estrogen receptor (ER). Conversely, we postulate that estrogen deprivation in postmenopausal women attenuates growth hormone (GH) secretion and insulin-like growth factor-1 (IGF-I) production, thus favoring development of metabolic syndrome in men treated with toremifene, a new estrogen antagonist used adjunctively in prostatic cancer
Read the detailed description
Systemic concentrations of Te, E2, GH, IGF-I and insulin growth factor binding protein 3 (IGFBP-3) decline in healthy aging men and women. Relative sex-steroid deprivation accentuates GH and IGF-I depletion, since Te stimulates GH and IGF-I production in older men, hypogonadal males of all ages, and patients undergoing (genotypic female-to-male) gender reassignment. The estrogen-receptor antagonist, tamoxifen, blocks this effect of Te, suggesting involvement of E2 in GH's stimulation at least in young men. E2 alone stimulates GH secretion in young and older women. Because Te is converted to E2 by aromatization in the body, we postulate that E2 is the active moiety in both men and women. Moreover, we hypothesize that the decline of E2 in older men and women contributes to the fall in GH output. These basic concepts will be tested here.
- Conditions
- Normal Healthy Volunteers
- Being tested
- Toremifene, Placebo, GHRH/Ghrelin combined Injection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ToremifeneDrug
PlaceboDrug
GHRH/Ghrelin combined InjectionDrug
| Study group | Role | What they receive |
|---|---|---|
| Oral Toremifene/Oral Placebo | Experimental | Oral toremifene will be given once on Day 1 and continue daily x10 days. A single combined IV injection of growth hormone releasing hormone (GHRH)/ghrelin (both doses 0.3mcg/kg) will be given on the overnight visit.
After at least 3 weeks, subjects will return to receive oral placebo on Day 1 and continue daily x10 days. A single combined IV injection of GHRH/ghrelin (both doses 0.3mcg/kg) will be given on the overnight visit. Receives: Drug: Toremifene; Drug: Placebo; Drug: GHRH/Ghrelin combined Injection |
| Oral Placebo/Oral Toremifene | Experimental | Oral placebo will be given once on Day 1 and continue daily x10 days. A single combined IV injection of GHRH/ghrelin (both doses 0.3mcg/kg) will be given on the overnight visit.
After at least 3 weeks, subjects will return to receive oral toremifene on Day 1 and continue daily x10 days. A single combined IV injection of GHRH/ghrelin (both doses 0.3mcg/kg) will be given on the overnight visit. Receives: Drug: Toremifene; Drug: Placebo; Drug: GHRH/Ghrelin combined Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Summed mass of growth hormone over 10 hours
Subjects will be given toremifene/placebo on Day 1 to take for 10 days. For one night between Days 8-12, from date of randomization, subjects will undergo a 12-h overnight (2200-1000h) fasting, every 10-min blood sampling. The primary analytical outcome is the summed mass of growth hormone (ie. mean/min/max) secreted in pulses over the first 10h of overnight blood samples. Pulsatile growth hormone is relevant, since sex-steroid hormones and regulatory peptides uniquely control growth hormone secretory-burst mass
Measured: Participants will be followed for an average of 2 months with growth hormone measurements occuring 10 days after initiating study medication administration.
Secondary outcomes (1)
Growth hormone responsiveness over last 2h
Subjects will be given toremifene/placebo on Day 1 to take for 10 days. For one night between Days 8-12, from date of randomization, subjects will undergo a 12-h overnight (2200-1000h) fasting, every 10-min blood sampling. The secondary analytical outcome is growth hormone responsiveness over the last 2 hours to bolus GHRH/ghrelin stimulation (ie. mean/min/max).
Measured: Participants will be followed for an average of 2 months with growth hormone measurements occuring 10 days after initiating study medication administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2014 (estimated)
- Study startDec 2014
- Primary completionMay 2016
- Study completionMay 2016
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
- 40 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
- NCT02271282
- Sponsor's protocol ID
- 14-004704
- Status last verified
- Sep 2016
- First submitted
- 17 Oct 2014
- Last updated
- 14 Sep 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Estradiol-Receptor Blockade in Older Men and Women
- ClinicalTrials.gov ID
- NCT02271282
- Acronym / sponsor ID
- 14-004704
- Conditions
- Normal Healthy Volunteers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- Dec 2014
- Primary completion
- May 2016 (actual)
- Study completion
- May 2016 (actual)
- First posted
- 22 Oct 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.
Repletion of testosterone (Te) in older men drives GH secretion after its aromatization to estradiol (E2), which acts via the estrogen receptor (ER). Conversely, we postulate that estrogen deprivation in postmenopausal women attenuates growth hormone (GH) secretion and insulin-like growth factor-1 (IGF-I) production, thus favoring development of metabolic syndrome in men treated with toremifene, a new estrogen antagonist used adjunctively in prostatic cancer
Detailed description
Systemic concentrations of Te, E2, GH, IGF-I and insulin growth factor binding protein 3 (IGFBP-3) decline in healthy aging men and women. Relative sex-steroid deprivation accentuates GH and IGF-I depletion, since Te stimulates GH and IGF-I production in older men, hypogonadal males of all ages, and patients undergoing (genotypic female-to-male) gender reassignment. The estrogen-receptor antagonist, tamoxifen, blocks this effect of Te, suggesting involvement of E2 in GH's stimulation at least in young men. E2 alone stimulates GH secretion in young and older women. Because Te is converted to E2 by aromatization in the body, we postulate that E2 is the active moiety in both men and women. Moreover, we hypothesize that the decline of E2 in older men and women contributes to the fall in GH output. These basic concepts will be tested here.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Oral Toremifene/Oral Placebo | Experimental | Drug: Toremifene, Drug: Placebo, Drug: GHRH/Ghrelin combined InjectionOral toremifene will be given once on Day 1 and continue daily x10 days. A single combined IV injection of growth hormone releasing hormone (GHRH)/ghrelin (both doses 0.3mcg/kg) will be given on the overnight visit. After at least 3 weeks, subjects will return to receive oral placebo on Day 1 and continue daily x10 days. A single combined IV injection of GHRH/ghrelin (both doses 0.3mcg/kg) will be given on the overnight visit. |
| Oral Placebo/Oral Toremifene | Experimental | Drug: Toremifene, Drug: Placebo, Drug: GHRH/Ghrelin combined InjectionOral placebo will be given once on Day 1 and continue daily x10 days. A single combined IV injection of GHRH/ghrelin (both doses 0.3mcg/kg) will be given on the overnight visit. After at least 3 weeks, subjects will return to receive oral toremifene on Day 1 and continue daily x10 days. A single combined IV injection of GHRH/ghrelin (both doses 0.3mcg/kg) will be given on the overnight visit. |
Who may qualify
- Ages
- 50 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 40 healthy women and men (ages 50 to 80 y); women will be post-menopausal (clinically defined by E2 < 50 pg/mL, FSH > 30Iu/L)
- BMI 18-35 kg/m2
- community dwelling; and voluntarily consenting
Key exclusion criteria (15 listed)
- recent use of psychotropic or neuroactive drugs (within five biological half-live);
- obesity (outside weight range above);
- Laboratory test results not deemed physician acceptable, viz potassium <3.5 mEq/L, magnesium <1.5 mEq/L, triglycerides > 300, BUN >30 or creatinine > 1.5 mg/dL, liver functions tests twice upper limit of normal, anemia (hemoglobin must meet Blood Bank requirements - Hgb ≥ 12.5 g/dL)
- drug or alcohol abuse, psychosis, depression, mania or severe anxiety;
- acute or chronic organ-system disease, including renal failure (creatinine > 1.5 mg/dL)
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 |
|---|---|---|
| Toremifene | Drug | Oral Placebo/Oral Toremifene, Oral Toremifene/Oral Placebo |
| Placebo | Drug | Oral Placebo/Oral Toremifene, Oral Toremifene/Oral Placebo |
| GHRH/Ghrelin combined Injection | Drug | Oral Placebo/Oral Toremifene, Oral Toremifene/Oral Placebo |
Primary outcome
Summed mass of growth hormone over 10 hours
Time frame: Participants will be followed for an average of 2 months with growth hormone measurements occuring 10 days after initiating study medication administration.
Subjects will be given toremifene/placebo on Day 1 to take for 10 days. For one night between Days 8-12, from date of randomization, subjects will undergo a 12-h overnight (2200-1000h) fasting, every 10-min blood sampling. The primary analytical outcome is the summed mass of growth hormone (ie. mean/min/max) secreted in pulses over the first 10h of overnight blood samples. Pulsatile growth hormone is relevant, since sex-steroid hormones and regulatory peptides uniquely control growth hormone secretory-burst mass
1 secondary outcome
Growth hormone responsiveness over last 2h
Time frame: Participants will be followed for an average of 2 months with growth hormone measurements occuring 10 days after initiating study medication administration
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 14 Sep 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 Toremifene and GHRH/Ghrelin combined Injection 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 15 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 14 Sep 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?
Summed mass of growth hormone over 10 hours (time frame: Participants will be followed for an average of 2 months with growth hormone measurements occuring 10 days after initiating study medication administration.). 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 14 Sep 2016; AzTrials last refreshed its copy on 7 Nov 2026.