Testosterone DeficiencyNCT01963390
Metabolomics During Testosterone Therapy
An observational study of Testosterone Deficiency, run by Men's Health Boston at 1 site in United States.
Trial summary
One promising but understudied area in the field of testosterone (T) therapy is its effect on metabolism and the development of type II diabetes. Metabolomics is a powerful research tool that can detect very early signs of metabolic derangement that may lead to metabolic disease. Read more about this study
- Who is it for?
- Ages 20 to 90 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Testosterone Deficiency
- What is being tested?
- Testosterone Therapy
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2012to Dec 2017
- Phase
- Observational
- 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 20 to 90 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Study population: Testosterone deficient men who intend to undergo testosterone therapy at an outpatient men's health clinic.
Who may be able to join
- Symptomatic testosterone deficiency
- Intend to undergo testosterone therapy at Men's Health Boston
- Total testosterone <350ng/dL or free testosterone <1.5ng/dL
Who cannot join
- Type 1 diabetes
- Use of exogenous testosterone or clomiphene citrate
- Known karyotype abnormalities
- Seizure disorders
- Malignancy
Trial locations and contacts
1 site in 1 country.
United States1 site
Men's Health Boston
Chestnut Hill, Massachusetts, 02467
About this study
Official title: Testosterone Therapy and Its Effects on Metabolic Function
One promising but understudied area in the field of testosterone (T) therapy is its effect on metabolism and the development of type II diabetes. Metabolomics is a powerful research tool that can detect very early signs of metabolic derangement that may lead to metabolic disease. In this observational study, investigators aim to apply metabolomics in order to better understand how T therapy influences metabolism. In a clinical population of outpatient men with T deficiency investigators will perform comprehensive clinical evaluations and also obtain blood for metabolomics. This will be done once prior to T therapy and again after 4-6 months of T therapy. Investigators hypothesize that they can detect metabolic derangements in men with T deficiency and that these derangements will improve with T therapy.
Read the detailed description
One promising but understudied area in the field of T therapy is its effect on insulin resistance (IR) and the development of type II diabetes and cardiometabolic disease. Although several clinical studies suggest T therapy improves metabolic parameters and may prevent disease progression, a mechanism for understanding this process is lacking. Investigators propose to use metabolomics to shed light on how metabolic function changes with T therapy.
Metabolomics is an established investigative tool that measures hundreds of unique chemical markers (metabolites) involved in normal and diseased cellular processes from a blood sample. Previous studies using the Metabolite Profiling Platform at the Broad Institute of Harvard/Massachusetts Institute of Technology applied tandem liquid chromatography-mass spectrometry (LC-MS)-based metabolomics to large, population-based cohorts. These studies identified and validated highly sensitive signatures of IR that successfully predicted occult risk for type II diabetes in clinically normal men. Investigators now plan to apply metabolomics to a clinical population in order to obtain a new perspective on the biochemical metabolic changes that occur based on a man's testosterone status. Investigators plan to study men with symptomatic testosterone deficiency identified at Men's Health Boston (MHB), an outpatient men's health clinic.
In a pilot study involving 32 blood samples, investigators have already identified a specific metabolomic signature in men undergoing androgen deprivation therapy for prostate cancer. Based on these preliminary results and other recent studies, investigators hypothesize that they can detect metabolic derangements in men with T deficiency and that these derangements will respond to changes in T levels. Investigators will address this hypothesis though the following specific aims:
Aim 1: To characterize metabolite profiles and evaluate metabolic dysfunction in T deficient men
To accomplish this aim investigators will study T deficient men presenting to MHB. In addition to metabolite profiling, these men will undergo a comprehensive clinical evaluation at MHB including:
- Complete History and Physical exam
- Assessment of symptoms of T deficiency and sexual function using validated and other questionnaires
- Comprehensive hormonal and metabolic laboratory evaluation
- Body composition (including visceral and subcutaneous adiposity) by dual x-ray absorptiometry (DXA) Investigators will build a reference dataset relating metabolite profiles with metabolic risk factors in a clinical population of T deficient men. This will include data on the relationship between metabolite profiles and sexual and other symptoms of T deficiency. Investigators will also compare concentrations of select metabolites between T deficient men and matched eugonadal controls previously studied in the Framingham cohort.
Aim 2: To determine how T therapy influences metabolite profiles and IR
- To identify metabolites that change in response to raising serum T
- To determine how changes in metabolite profiles relate to changes in IR
- To determine how response in terms of sexual function symptoms of low T relate to response in metabolite profiles and IR.
Metabolite profiles will be obtained and clinical evaluation performed (described above under Aim1) at baseline and again after 6 months of therapy. Investigators will study interactions between changes in sexual function and serum T, IR, body composition and metabolite profiles (with particular attention to established metabolite markers of IR).
- Conditions
- Testosterone Deficiency
- Being tested
- Testosterone Therapy
- Keywords
- Hypogonadism, Testosterone Deficiency
- Medical subject headings
- Hypogonadism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Testosterone TherapyDrug
In this observational study we will be enrolling testosterone deficient men who intend to undergo testosterone therapy.
| Study group | Role | What they receive |
|---|---|---|
| Testosterone therapy | The study population is a cohort of testosterone deficient men who are planning on undergoing testosterone therapy at an outpatient men's health clinic. Receives: Drug: Testosterone Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Metabolomics
Blood samples will be sent to the Metabolite Profiling Platform at the Broad Institute of Harvard/Massachusetts Institute of Technology. Metabolomics measures hundreds of unique chemical markers (metabolites) involved in normal and diseased cellular processes from a blood sample. These metabolites include branched chain and aromatic amino acids, ketoacids, and triacylglycerides.
Measured: After 4-6 mo of therapy
Metabolomics
Blood samples will be sent to the Metabolite Profiling Platform at the Broad Institute of Harvard/Massachusetts Institute of Technology. Metabolomics measures hundreds of unique chemical markers (metabolites) involved in normal and diseased cellular processes from a blood sample. These metabolites include branched chain and aromatic amino acids, ketoacids, and triacylglycerides.
Measured: Baseline
Secondary outcomes (8)
Symptoms of Testosterone Deficiency
Symptoms of T deficiency will be assessed using the clinical history and using validated and other questionnaires.
Measured: After 4-6mo of T therapy
Body Composition
Body composition, including visceral and subcutaneous adiposity, will be determined using dual energy x-ray absorptiometry (DXA)
Measured: After 4-6mo of T therapy
Fasting insulin and glucose
Insulin and glucose will be determined from a fasting blood sample.
Measured: After 4-6mo of T therapy
Lipid Profile
A clinical lipid profile including LDL, HDL, and total triglycerides will be obtained from a fasting blood sample.
Measured: After 4-6mo of T therapy
Symptoms of Testosterone Deficiency
Symptoms of T deficiency will be assessed using the clinical history and using validated and other questionnaires.
Measured: Baseline
Body Composition
Body composition, including visceral and subcutaneous adiposity, will be determined using dual energy x-ray absorptiometry (DXA)
Measured: Baseline
Fasting insulin and glucose
Insulin and glucose will be determined from a fasting blood sample.
Measured: Baseline
Lipid Profile
A clinical lipid profile including LDL, HDL, and total triglycerides will be obtained from a fasting blood sample.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2013 (estimated)
- Study startJul 2012
- Primary completionJun 2017
- Study completionDec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Testosterone DeficiencyStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Men's Health Boston
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Abraham Morgentaler, MD, Principal investigator, Men's Health BostonRavi Kacker, MD, Study director, Men's Health Boston
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01963390
- Sponsor's protocol ID
- 2012P000184
- Status last verified
- Apr 2018
- First submitted
- 13 Oct 2013
- Last updated
- 19 Apr 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Cheng S, Rhee EP, Larson MG, Lewis GD, McCabe EL, Shen D, Palma MJ, Roberts LD, Dejam A, Souza AL, Deik AA, Magnusson M, Fox CS, O'Donnell CJ, Vasan RS, Melander O, Clish CB, Gerszten RE, Wang TJ. Metabolite profiling identifies pathways associated with metabolic risk in humans. Circulation. 2012 May 8;125(18):2222-31. doi: 10.1161/CIRCULATIONAHA.111.067827. Epub 2012 Apr 11.
PubMed 22496159Wang TJ, Larson MG, Vasan RS, Cheng S, Rhee EP, McCabe E, Lewis GD, Fox CS, Jacques PF, Fernandez C, O'Donnell CJ, Carr SA, Mootha VK, Florez JC, Souza A, Melander O, Clish CB, Gerszten RE. Metabolite profiles and the risk of developing diabetes. Nat Med. 2011 Apr;17(4):448-53. doi: 10.1038/nm.2307. Epub 2011 Mar 20.
PubMed 21423183Rhee EP, Cheng S, Larson MG, Walford GA, Lewis GD, McCabe E, Yang E, Farrell L, Fox CS, O'Donnell CJ, Carr SA, Vasan RS, Florez JC, Clish CB, Wang TJ, Gerszten RE. Lipid profiling identifies a triacylglycerol signature of insulin resistance and improves diabetes prediction in humans. J Clin Invest. 2011 Apr;121(4):1402-11. doi: 10.1172/JCI44442. Epub 2011 Mar 14.
PubMed 21403394Kapoor D, Goodwin E, Channer KS, Jones TH. Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes. Eur J Endocrinol. 2006 Jun;154(6):899-906. doi: 10.1530/eje.1.02166.
PubMed 16728551Heufelder AE, Saad F, Bunck MC, Gooren L. Fifty-two-week treatment with diet and exercise plus transdermal testosterone reverses the metabolic syndrome and improves glycemic control in men with newly diagnosed type 2 diabetes and subnormal plasma testosterone. J Androl. 2009 Nov-Dec;30(6):726-33. doi: 10.2164/jandrol.108.007005. Epub 2009 Jul 3.
PubMed 19578132
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Testosterone Therapy and Its Effects on Metabolic Function
- ClinicalTrials.gov ID
- NCT01963390
- Acronym / sponsor ID
- 2012P000184
- Conditions
- Testosterone Deficiency
- Keywords
- Hypogonadism, Testosterone Deficiency
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Men's Health BostonUniversity, hospital or other
- Study start
- Jul 2012
- Primary completion
- Jun 2017 (actual)
- Study completion
- Dec 2017 (actual)
- First posted
- 16 Oct 2013 (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.
One promising but understudied area in the field of testosterone (T) therapy is its effect on metabolism and the development of type II diabetes. Metabolomics is a powerful research tool that can detect very early signs of metabolic derangement that may lead to metabolic disease. In this observational study, investigators aim to apply metabolomics in order to better understand how T therapy influences metabolism. In a clinical population of outpatient men with T deficiency investigators will perform comprehensive clinical evaluations and also obtain blood for metabolomics. This will be done once prior to T therapy and again after 4-6 months of T therapy. Investigators hypothesize that they can detect metabolic derangements in men with T deficiency and that these derangements will improve with T therapy.
Detailed description
One promising but understudied area in the field of T therapy is its effect on insulin resistance (IR) and the development of type II diabetes and cardiometabolic disease. Although several clinical studies suggest T therapy improves metabolic parameters and may prevent disease progression, a mechanism for understanding this process is lacking. Investigators propose to use metabolomics to shed light on how metabolic function changes with T therapy.
Metabolomics is an established investigative tool that measures hundreds of unique chemical markers (metabolites) involved in normal and diseased cellular processes from a blood sample. Previous studies using the Metabolite Profiling Platform at the Broad Institute of Harvard/Massachusetts Institute of Technology applied tandem liquid chromatography-mass spectrometry (LC-MS)-based metabolomics to large, population-based cohorts. These studies identified and validated highly sensitive signatures of IR that successfully predicted occult risk for type II diabetes in clinically normal men. Investigators now plan to apply metabolomics to a clinical population in order to obtain a new perspective on the biochemical metabolic changes that occur based on a man's testosterone status. Investigators plan to study men with symptomatic testosterone deficiency identified at Men's Health Boston (MHB), an outpatient men's health clinic.
In a pilot study involving 32 blood samples, investigators have already identified a specific metabolomic signature in men undergoing androgen deprivation therapy for prostate cancer. Based on these preliminary results and other recent studies, investigators hypothesize that they can detect metabolic derangements in men with T deficiency and that these derangements will respond to changes in T levels. Investigators will address this hypothesis though the following specific aims:
Aim 1: To characterize metabolite profiles and evaluate metabolic dysfunction in T deficient men
To accomplish this aim investigators will study T deficient men presenting to MHB. In addition to metabolite profiling, these men will undergo a comprehensive clinical evaluation at MHB including:
- Complete History and Physical exam
- Assessment of symptoms of T deficiency and sexual function using validated and other questionnaires
- Comprehensive hormonal and metabolic laboratory evaluation
- Body composition (including visceral and subcutaneous adiposity) by dual x-ray absorptiometry (DXA) Investigators will build a reference dataset relating metabolite profiles with metabolic risk factors in a clinical population of T deficient men. This will include data on the relationship between metabolite profiles and sexual and other symptoms of T deficiency. Investigators will also compare concentrations of select metabolites between T deficient men and matched eugonadal controls previously studied in the Framingham cohort.
Aim 2: To determine how T therapy influences metabolite profiles and IR
- To identify metabolites that change in response to raising serum T
- To determine how changes in metabolite profiles relate to changes in IR
- To determine how response in terms of sexual function symptoms of low T relate to response in metabolite profiles and IR.
Metabolite profiles will be obtained and clinical evaluation performed (described above under Aim1) at baseline and again after 6 months of therapy. Investigators will study interactions between changes in sexual function and serum T, IR, body composition and metabolite profiles (with particular attention to established metabolite markers of IR).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Testosterone therapy | – | Drug: Testosterone TherapyThe study population is a cohort of testosterone deficient men who are planning on undergoing testosterone therapy at an outpatient men's health clinic. |
Who may qualify
- Ages
- 20 to 90 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Testosterone deficient men who intend to undergo testosterone therapy at an outpatient men's health clinic.
Key inclusion criteria (3 listed)
- Symptomatic testosterone deficiency
- Intend to undergo testosterone therapy at Men's Health Boston
- Total testosterone <350ng/dL or free testosterone <1.5ng/dL
Key exclusion criteria (5 listed)
- Type 1 diabetes
- Use of exogenous testosterone or clomiphene citrate
- Known karyotype abnormalities
- Seizure disorders
- Malignancy
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 |
|---|---|---|
| Testosterone TherapyIn this observational study we will be enrolling testosterone deficient men who intend to undergo testosterone therapy. | Drug | Testosterone therapy |
Primary outcome
Metabolomics
Time frame: After 4-6 mo of therapy
Blood samples will be sent to the Metabolite Profiling Platform at the Broad Institute of Harvard/Massachusetts Institute of Technology. Metabolomics measures hundreds of unique chemical markers (metabolites) involved in normal and diseased cellular processes from a blood sample. These metabolites include branched chain and aromatic amino acids, ketoacids, and triacylglycerides.
Metabolomics
Time frame: Baseline
Blood samples will be sent to the Metabolite Profiling Platform at the Broad Institute of Harvard/Massachusetts Institute of Technology. Metabolomics measures hundreds of unique chemical markers (metabolites) involved in normal and diseased cellular processes from a blood sample. These metabolites include branched chain and aromatic amino acids, ketoacids, and triacylglycerides.
8 secondary outcomes
Symptoms of Testosterone Deficiency
Time frame: After 4-6mo of T therapy
Body Composition
Time frame: After 4-6mo of T therapy
Fasting insulin and glucose
Time frame: After 4-6mo of T therapy
Lipid Profile
Time frame: After 4-6mo of T therapy
Symptoms of Testosterone Deficiency
Time frame: Baseline
Body Composition
Time frame: Baseline
Fasting insulin and glucose
Time frame: Baseline
Lipid Profile
Time frame: Baseline
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 19 Apr 2018.
- Background: PubMed 22496159Cheng S, Rhee EP, Larson MG, Lewis GD, McCabe EL, Shen D, Palma MJ, Roberts LD, Dejam A, Souza AL, Deik AA, Magnusson M, Fox CS, O'Donnell CJ, Vasan RS, Melander O, Clish CB, Gerszten RE, Wang TJ. Metabolite profiling identifies pathways associated with metabolic risk in humans. Circulation. 2012 May 8;125(18):2222-31. doi: 10.1161/CIRCULATIONAHA.111.067827. Epub 2012 Apr 11.
- Background: PubMed 21423183Wang TJ, Larson MG, Vasan RS, Cheng S, Rhee EP, McCabe E, Lewis GD, Fox CS, Jacques PF, Fernandez C, O'Donnell CJ, Carr SA, Mootha VK, Florez JC, Souza A, Melander O, Clish CB, Gerszten RE. Metabolite profiles and the risk of developing diabetes. Nat Med. 2011 Apr;17(4):448-53. doi: 10.1038/nm.2307. Epub 2011 Mar 20.
- Background: PubMed 21403394Rhee EP, Cheng S, Larson MG, Walford GA, Lewis GD, McCabe E, Yang E, Farrell L, Fox CS, O'Donnell CJ, Carr SA, Vasan RS, Florez JC, Clish CB, Wang TJ, Gerszten RE. Lipid profiling identifies a triacylglycerol signature of insulin resistance and improves diabetes prediction in humans. J Clin Invest. 2011 Apr;121(4):1402-11. doi: 10.1172/JCI44442. Epub 2011 Mar 14.
- Background: PubMed 16728551Kapoor D, Goodwin E, Channer KS, Jones TH. Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes. Eur J Endocrinol. 2006 Jun;154(6):899-906. doi: 10.1530/eje.1.02166.
- Background: PubMed 19578132Heufelder AE, Saad F, Bunck MC, Gooren L. Fifty-two-week treatment with diet and exercise plus transdermal testosterone reverses the metabolic syndrome and improves glycemic control in men with newly diagnosed type 2 diabetes and subnormal plasma testosterone. J Androl. 2009 Nov-Dec;30(6):726-33. doi: 10.2164/jandrol.108.007005. Epub 2009 Jul 3.
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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.
Abraham Morgentaler, MD principal investigator
Men's Health Boston
Ravi Kacker, MD study director
Men's Health Boston
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Testosterone Deficiency, run by Men's Health Boston 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 5 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 19 Apr 2018. 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?
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?
Metabolomics (time frame: After 4-6 mo of therapy). The study lists 2 primary outcomes in all. 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 NCT01963390, which also lists 5 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 19 Apr 2018.