Healthy VolunteersNCT00114114
Dose-Response of Gonadal Steroids and Bone Turnover in Older Men
A study testing Testosterone and Goserelin acetate in people with Healthy Volunteers, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
The purpose of this study is to determine the levels of testosterone and/or estradiol at which changes in bone turnover, body composition, strength, sexual function etc. begin to occur in older men. This information may help determine when to intervene with hormone replacement therapy in aging men. Read more about this study
- Who is it for?
- Ages 60 to 75 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- Testosterone and Goserelin acetate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 177 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2004to 1 Nov 2017
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 60 to 75 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy men age 60 to 75
Who cannot join
- History of significant cardiac, renal, pulmonary, hepatic, benign prostatic hyperplasia, or malignant disease, current alcohol or illicit drug abuse, or major psychiatric disorders.
- Current diagnoses of disorders known to affect bone metabolism including hyperthyroidism, hyperparathyroidism, osteomalacia, or Paget's disease.
- Current use of medications known to affect bone metabolism including estrogens, androgens, anti-estrogens, bisphosphonates, calcitonin, fluoride, oral or inhaled glucocorticoids, suppressive doses of thyroxine, lithium, pharmacological doses of vitamin D (greater than 2000 IU/day), or anti-convulsants.
- Cognitive or intellectual impairment that precludes complete understanding of the study protocol.
- History of deep vein thrombosis, pulmonary embolism, or clotting disorders.
- Serum 25-hydroxyvitamin D < 15 ng/mL
Show all 22Show fewer
- Serum parathyroid hormone (PTH) < 10 or > 65 pg/mL
- Serum thyroid stimulating hormone (TSH) < 0.5 or > 5.0 U/L
- Serum calcium > 10.6 mg/dL
- Serum creatinine > 2 mg/dL
- Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 2x the upper limit of normal
- Serum bilirubin > 2 mg/dL
- Serum alkaline phosphatase > 150 U/L
- Plasma hemoglobin < 11 gm/dL
- Hematocrit > 50
- Fracture within the last 6 months.
- Serum testosterone level < 270 or > 1070 ng/dL
- Serum prostate specific antigen (PSA) level > 4 ug/L.
- International Prostate Symptom Score (IPSS) > 19
- Systolic blood pressure > 160 or diastolic blood pressure > 95
- Framingham risk score greater than or equal to 20
- Difficulty walking 2 blocks
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
The purpose of this study is to determine the levels of testosterone and/or estradiol at which changes in bone turnover, body composition, strength, sexual function etc. begin to occur in older men. This information may help determine when to intervene with hormone replacement therapy in aging men.
Read the detailed description
In this protocol, men age 60-75 will be randomized to one of 6 groups. Groups 1-5 will receive goserelin acetate (Zoladex) plus 0 (placebo gel), 1.25, 2.5, 5, or 10* g/day of testosterone gel (Androgel). Group 6 will receive placebos for both goserelin acetate and testosterone gel. (*Note that the 10 g/day dose was reduced to 7.5 g/day part-way through the trial due to reports of possible increased risk of cardiovascular events with testosterone administration).
Subjects will be blinded with respect to group assignment. Dietary calcium intake will be assessed by a research dietitian and adjustments made through diet or supplements so that calcium intake is between 1000 and 1200 mg/day.
Subjects will be seen on the Clinical Research Center at 4 week intervals for 16 weeks (0, 4, 8, 12, and 16 weeks). At each visit, compliance with Androgel will be assessed by reviewing a medication diary. A standardized series of questions will be posed to each subject to assess potential side effects of the study drugs. Subjects receiving Androgel' will be given a new 4 week supply of medication (except at week 16). A fasting blood and second voided urine sample will be collected. After the blood and urine samples have been obtained, subjects will be given their goserelin injection. The blood and urine tests listed below as well as anthropometric measures, and questionnaires will be performed at each visit. Dual-energy x-ray absorptiometry (DXA), quantitate computed tomography (QCT) scans, and strength assessments will be performed at 0 and 16 weeks only. Subjects who discontinue participation at or after week 8 will be asked if they are willing to have an early discontinuation visit in which all procedures normally done at week 16 will be performed.
The following measures will be assessed:
- Routine chemistries and prostate specific antigen, PSA (for safety assessment)
- Bone turnover using blood and urine tests
- Hormones
- Lipids
- Body composition
- Strength
- Sexual desire and erectile function
- Bone mineral density and bone microarchitecture
- Conditions
- Healthy Volunteers
- Being tested
- Testosterone, Goserelin acetate
- Keywords
- Testosterone, Bone turnover, Aging, Body composition, Hypogonadism, Sexual function
- Medical subject headings
- Hypogonadism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TestosteroneDrug
Also called Androgel
Androgel placebo or 1.25, 2.5, 5. or 10* gms topically each day
Goserelin acetateDrug
Also called Zoladex
3.6 gms sc every 4 weeks
| Study group | Role | What they receive |
|---|---|---|
| Group 1: 0 g/day | Experimental | Zoladex plus Placebo Testosterone (T) gel Receives: Drug: Testosterone; Drug: Goserelin acetate |
| Group 2: 1.25 g/day | Experimental | Zoladex plus 1.25 g/day T gel Receives: Drug: Testosterone; Drug: Goserelin acetate |
| Group 3: 2.5 g/day | Experimental | Zoladex plus 2.5 g/day T gel Receives: Drug: Testosterone; Drug: Goserelin acetate |
| Group 4: 5 g/day | Experimental | Zoladex plus 5 g/day T gel Receives: Drug: Testosterone; Drug: Goserelin acetate |
| Group 5: 10* g/day | Experimental | Zoladex plus 10* g/day T gel. *Note that the 10 g/day dose was reduced to 7.5 g/day part-way through the trial Receives: Drug: Testosterone; Drug: Goserelin acetate |
| Group 6: Placebo/Placebo (PBO/PBO) | Experimental | Placebo Zoladex plus Placebo T gel (controls) Receives: Drug: Testosterone; Drug: Goserelin acetate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change in Bone Turnover Marker (Serum C-telopeptide, CTX)
Measured: Baseline and 16 weeks
Secondary outcomes (4)
Percentage Change in Body Composition: Fat Mass
Measured: Baseline and 16 weeks
Percentage Change in Thigh Muscle Area
Assessed by quantitative computed tomography (QCT)
Measured: Baseline and 16 weeks
Change in Erectile Function Symptoms
Based on International Index of Erectile Function (IIEF) scale, question #15, which asked subjects to rate their confidence that they could achieve and maintain an erection. Scores range from 1 to 5, with higher scores being better.
Measured: Baseline and 16 weeks
Change in Libido / Sexual Desire
Change in libido from baseline (scale ranges from -2 to +2), with -2 being much less, -1 somewhat less, 0 same, +1 somewhat more, +2 much more
Measured: 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2005 (estimated)
- Study startSep 2004
- Primary completion1 Nov 2017
- Study completion1 Nov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe 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 N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 177 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA), Solvay Pharmaceuticals, AstraZeneca, AbbVie
- Responsible party
- Principal investigator, Benjamin Leder, MD, Massachusetts General Hospital
- Investigators
- Ben Z Leder, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00114114
- Sponsor's protocol ID
- 2003-P-001868
- Other IDs
- R01AG030545
- Status last verified
- Sep 2019
- First submitted
- 13 Jun 2005
- Last updated
- 8 Oct 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Finkelstein JS, Lee H, Burnett-Bowie SM, Darakananda K, Gentile EC, Goldstein DW, Prizand SH, Krivicich LM, Taylor AP, Wulczyn KE, Leder BZ, Yu EW. Dose-Response Relationships Between Gonadal Steroids and Bone, Body Composition, and Sexual Function in Aging Men. J Clin Endocrinol Metab. 2020 Aug 1;105(8):2779-88. doi: 10.1210/clinem/dgaa318.
PubMed 32480409Bachmann KN, Huang S, Lee H, Dichtel LE, Gupta DK, Burnett JC Jr, Miller KK, Wang TJ, Finkelstein JS. Effect of Testosterone on Natriuretic Peptide Levels. J Am Coll Cardiol. 2019 Mar 26;73(11):1288-1296. doi: 10.1016/j.jacc.2018.12.062.
PubMed 30898204Finkelstein JS, Lee H, Leder BZ, Burnett-Bowie SA, Goldstein DW, Hahn CW, Hirsch SC, Linker A, Perros N, Servais AB, Taylor AP, Webb ML, Youngner JM, Yu EW. Gonadal steroid-dependent effects on bone turnover and bone mineral density in men. J Clin Invest. 2016 Mar 1;126(3):1114-25. doi: 10.1172/JCI84137. Epub 2016 Feb 22.
PubMed 26901812Finkelstein JS, Lee H, Burnett-Bowie SA, Pallais JC, Yu EW, Borges LF, Jones BF, Barry CV, Wulczyn KE, Thomas BJ, Leder BZ. Gonadal steroids and body composition, strength, and sexual function in men. N Engl J Med. 2013 Sep 12;369(11):1011-22. doi: 10.1056/NEJMoa1206168.
PubMed 24024838
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dose-Response of Gonadal Steroids and Bone Turnover in Older Men
- ClinicalTrials.gov ID
- NCT00114114
- Acronym / sponsor ID
- 2003-P-001868
- Conditions
- Healthy Volunteers
- Keywords
- Testosterone, Bone turnover, Aging, Body composition, Hypogonadism, Sexual function
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 177 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA), Solvay Pharmaceuticals, AstraZeneca, AbbVie
- Study start
- Sep 2004
- Primary completion
- 1 Nov 2017 (actual)
- Study completion
- 1 Nov 2017 (actual)
- First posted
- 14 Jun 2005 (estimated)
- Results
- Posted 17 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the levels of testosterone and/or estradiol at which changes in bone turnover, body composition, strength, sexual function etc. begin to occur in older men. This information may help determine when to intervene with hormone replacement therapy in aging men.
Detailed description
In this protocol, men age 60-75 will be randomized to one of 6 groups. Groups 1-5 will receive goserelin acetate (Zoladex) plus 0 (placebo gel), 1.25, 2.5, 5, or 10* g/day of testosterone gel (Androgel). Group 6 will receive placebos for both goserelin acetate and testosterone gel. (*Note that the 10 g/day dose was reduced to 7.5 g/day part-way through the trial due to reports of possible increased risk of cardiovascular events with testosterone administration).
Subjects will be blinded with respect to group assignment. Dietary calcium intake will be assessed by a research dietitian and adjustments made through diet or supplements so that calcium intake is between 1000 and 1200 mg/day.
Subjects will be seen on the Clinical Research Center at 4 week intervals for 16 weeks (0, 4, 8, 12, and 16 weeks). At each visit, compliance with Androgel will be assessed by reviewing a medication diary. A standardized series of questions will be posed to each subject to assess potential side effects of the study drugs. Subjects receiving Androgel' will be given a new 4 week supply of medication (except at week 16). A fasting blood and second voided urine sample will be collected. After the blood and urine samples have been obtained, subjects will be given their goserelin injection. The blood and urine tests listed below as well as anthropometric measures, and questionnaires will be performed at each visit. Dual-energy x-ray absorptiometry (DXA), quantitate computed tomography (QCT) scans, and strength assessments will be performed at 0 and 16 weeks only. Subjects who discontinue participation at or after week 8 will be asked if they are willing to have an early discontinuation visit in which all procedures normally done at week 16 will be performed.
The following measures will be assessed:
- Routine chemistries and prostate specific antigen, PSA (for safety assessment)
- Bone turnover using blood and urine tests
- Hormones
- Lipids
- Body composition
- Strength
- Sexual desire and erectile function
- Bone mineral density and bone microarchitecture
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Group 1: 0 g/day | Experimental | Drug: Testosterone, Drug: Goserelin acetateZoladex plus Placebo Testosterone (T) gel |
| Group 2: 1.25 g/day | Experimental | Drug: Testosterone, Drug: Goserelin acetateZoladex plus 1.25 g/day T gel |
| Group 3: 2.5 g/day | Experimental | Drug: Testosterone, Drug: Goserelin acetateZoladex plus 2.5 g/day T gel |
| Group 4: 5 g/day | Experimental | Drug: Testosterone, Drug: Goserelin acetateZoladex plus 5 g/day T gel |
| Group 5: 10* g/day | Experimental | Drug: Testosterone, Drug: Goserelin acetateZoladex plus 10* g/day T gel. *Note that the 10 g/day dose was reduced to 7.5 g/day part-way through the trial |
| Group 6: Placebo/Placebo (PBO/PBO) | Experimental | Drug: Testosterone, Drug: Goserelin acetatePlacebo Zoladex plus Placebo T gel (controls) |
Who may qualify
- Ages
- 60 to 75 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Healthy men age 60 to 75
Key exclusion criteria (22 listed)
- History of significant cardiac, renal, pulmonary, hepatic, benign prostatic hyperplasia, or malignant disease, current alcohol or illicit drug abuse, or major psychiatric disorders.
- Current diagnoses of disorders known to affect bone metabolism including hyperthyroidism, hyperparathyroidism, osteomalacia, or Paget's disease.
- Current use of medications known to affect bone metabolism including estrogens, androgens, anti-estrogens, bisphosphonates, calcitonin, fluoride, oral or inhaled glucocorticoids, suppressive doses of thyroxine, lithium, pharmacological doses of vitamin D (greater than 2000 IU/day), or anti-convulsants.
- Cognitive or intellectual impairment that precludes complete understanding of the study protocol.
- History of deep vein thrombosis, pulmonary embolism, or clotting disorders.
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 |
|---|---|---|
| TestosteroneAlso: AndrogelAndrogel placebo or 1.25, 2.5, 5. or 10* gms topically each day | Drug | Group 1: 0 g/day, Group 2: 1.25 g/day, Group 3: 2.5 g/day, Group 4: 5 g/day, Group 5: 10* g/day, Group 6: Placebo/Placebo (PBO/PBO) |
| Goserelin acetateAlso: Zoladex3.6 gms sc every 4 weeks | Drug | Group 1: 0 g/day, Group 2: 1.25 g/day, Group 3: 2.5 g/day, Group 4: 5 g/day, Group 5: 10* g/day, Group 6: Placebo/Placebo (PBO/PBO) |
Primary outcome
Percent Change in Bone Turnover Marker (Serum C-telopeptide, CTX)
Time frame: Baseline and 16 weeks
4 secondary outcomes
Percentage Change in Body Composition: Fat Mass
Time frame: Baseline and 16 weeks
Percentage Change in Thigh Muscle Area
Time frame: Baseline and 16 weeks
Change in Erectile Function Symptoms
Time frame: Baseline and 16 weeks
Change in Libido / Sexual Desire
Time frame: 16 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32480409Finkelstein JS, Lee H, Burnett-Bowie SM, Darakananda K, Gentile EC, Goldstein DW, Prizand SH, Krivicich LM, Taylor AP, Wulczyn KE, Leder BZ, Yu EW. Dose-Response Relationships Between Gonadal Steroids and Bone, Body Composition, and Sexual Function in Aging Men. J Clin Endocrinol Metab. 2020 Aug 1;105(8):2779-88. doi: 10.1210/clinem/dgaa318.
- Derived from this study: PubMed 30898204Bachmann KN, Huang S, Lee H, Dichtel LE, Gupta DK, Burnett JC Jr, Miller KK, Wang TJ, Finkelstein JS. Effect of Testosterone on Natriuretic Peptide Levels. J Am Coll Cardiol. 2019 Mar 26;73(11):1288-1296. doi: 10.1016/j.jacc.2018.12.062.
- Derived from this study: PubMed 26901812Finkelstein JS, Lee H, Leder BZ, Burnett-Bowie SA, Goldstein DW, Hahn CW, Hirsch SC, Linker A, Perros N, Servais AB, Taylor AP, Webb ML, Youngner JM, Yu EW. Gonadal steroid-dependent effects on bone turnover and bone mineral density in men. J Clin Invest. 2016 Mar 1;126(3):1114-25. doi: 10.1172/JCI84137. Epub 2016 Feb 22.
- Derived from this study: PubMed 24024838Finkelstein JS, Lee H, Burnett-Bowie SA, Pallais JC, Yu EW, Borges LF, Jones BF, Barry CV, Wulczyn KE, Thomas BJ, Leder BZ. Gonadal steroids and body composition, strength, and sexual function in men. N Engl J Med. 2013 Sep 12;369(11):1011-22. doi: 10.1056/NEJMoa1206168.
Related trials for Healthy Volunteers
Not yet recruiting
Neuroergonomic Analysis of a Brain-Computer Interface Device (BCI)
Healthy Volunteers - Male and Female
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis
Not yet recruitingObservational study
Establishment of Biobank of Nasal Epithelium Samples From Healthy Volunteers
Healthy
RecruitingObservational study
Improved Methods of Cell Selection for Bone Marrow Transplant Alternatives
Graft-Versus-Host Disease, Graft-versus-leukemia
Not yet recruitingObservational study
Screening Protocol
Pain
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.
Ben Z Leder, MD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Testosterone and Goserelin acetate in people with Healthy Volunteers, run by Massachusetts General Hospital 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 1 inclusion and 22 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 8 Oct 2019. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Percent Change in Bone Turnover Marker (Serum C-telopeptide, CTX) (time frame: Baseline and 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00114114, which also lists 4 linked publications.
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 8 Oct 2019.