- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01963390
Metabolomics During Testosterone Therapy
Testosterone Therapy and Its Effects on Metabolic Function
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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Massachusetts
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Chestnut Hill, Massachusetts, United States, 02467
- Men's Health Boston
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- Symptomatic testosterone deficiency
- Intend to undergo testosterone therapy at Men's Health Boston
- Total testosterone <350ng/dL or free testosterone <1.5ng/dL
Exclusion Criteria:
- Type 1 diabetes
- Use of exogenous testosterone or clomiphene citrate
- Known karyotype abnormalities
- Seizure disorders
- Malignancy
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
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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.
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In this observational study we will be enrolling testosterone deficient men who intend to undergo testosterone therapy.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Metabolomics
Time Frame: After 4-6 mo of therapy
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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.
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After 4-6 mo of therapy
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Metabolomics
Time Frame: Baseline
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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.
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Baseline
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Symptoms of Testosterone Deficiency
Time Frame: After 4-6mo of T therapy
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Symptoms of T deficiency will be assessed using the clinical history and using validated and other questionnaires.
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After 4-6mo of T therapy
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Body Composition
Time Frame: After 4-6mo of T therapy
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Body composition, including visceral and subcutaneous adiposity, will be determined using dual energy x-ray absorptiometry (DXA)
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After 4-6mo of T therapy
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Fasting insulin and glucose
Time Frame: After 4-6mo of T therapy
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Insulin and glucose will be determined from a fasting blood sample.
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After 4-6mo of T therapy
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Lipid Profile
Time Frame: After 4-6mo of T therapy
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A clinical lipid profile including LDL, HDL, and total triglycerides will be obtained from a fasting blood sample.
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After 4-6mo of T therapy
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Symptoms of Testosterone Deficiency
Time Frame: Baseline
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Symptoms of T deficiency will be assessed using the clinical history and using validated and other questionnaires.
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Baseline
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Body Composition
Time Frame: Baseline
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Body composition, including visceral and subcutaneous adiposity, will be determined using dual energy x-ray absorptiometry (DXA)
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Baseline
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Fasting insulin and glucose
Time Frame: Baseline
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Insulin and glucose will be determined from a fasting blood sample.
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Baseline
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Lipid Profile
Time Frame: Baseline
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A clinical lipid profile including LDL, HDL, and total triglycerides will be obtained from a fasting blood sample.
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Baseline
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Ravi Kacker, MD, Men's Health Boston
Publications and helpful links
General Publications
- Kapoor 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.
- Wang 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.
- 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.
- Rhee 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.
- Heufelder 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2012P000184
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