HypogonadismPhase 4TERMSINFATNCT01123278
Testosterone Replacement in Metabolic Syndrome and Inflammation
A Phase 4 study testing Testosterone in people with Hypogonadism and Metabolic Syndrome, run by University of Roma La Sapienza at 2 sites in Italy.
Trial summary
Hypogonadism (HG) frequently complicates the Metabolic Syndrome (MetS), whether testosterone replacement (TRT) is beneficial has not been clearly ascertained. This study was designed to address the effects of TRT on insulin resistance, body composition and pro-inflammatory status in naïve patients with MetS and HG. Read more about this study
- Who is it for?
- Ages 18 to 75 years, men only
- Conditions the study is for
- Hypogonadism, Metabolic Syndrome, Obesity
- What is being tested?
- Testosterone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 82 participants
- Where
- 2 sitesItaly
- Study dates
- Jan 2004to Oct 2014
- Phase
- Phase 4
- 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 18 to 75 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- patients with Metabolic Syndrome according to ATPIII
- patients with mild hypogonadism (both testosterone evaluations between 6 and 11 nmol/L)
- patients naïve to hypoglycemic therapies
Who cannot join
- patients on hypoglycemic medications
- patients with severe hypogonadism (<5 nmol/L)
- patients with borderline T values hypogonadism (>11 nmol/L)
- patients with contraindication to testosterone therapy: prostate cancer, PSA>4 ng/ml, severe hepatic or renal insufficiency, Hb>17, Htc>52%, severe urinary retention
Trial locations and contacts
2 sites in 1 country.
Italy2 sites
Policlinico Umberto I Hospital - Sapienza University
Rome, Rome, 00161
Dipartimento di Fisiopatologia Medica - Policlinico Umberto I
Rome, 00161
About this study
Official title: Testosterone Replacement in Metabolic Syndrome and Inflammation of Fat Tissue
Hypogonadism (HG) frequently complicates the Metabolic Syndrome (MetS), whether testosterone replacement (TRT) is beneficial has not been clearly ascertained. This study was designed to address the effects of TRT on insulin resistance, body composition and pro-inflammatory status in naïve patients with MetS and HG.
Read the detailed description
The features of Metabolic Syndrome (MetS) include abdominal obesity, atherogenic dyslipidemia, raised blood pressure, insulin resistance or glucose intolerance. These symptoms are also frequently found in hypogonadal men.
Adipose tissue and androgens in male obesity are reciprocally linked. Total and free testosterone (T) are decreased in proportion to the degree of body fatness while T regulates insulin sensitivity and body composition. As a consequence, hypoandrogenism carries an additional independent risk for cardiovascular and metabolic disorders. Men with type 2 diabetes mellitus (T2D) exhibit lowered T levels that are inversely correlated to HbA1c. In addition, abdominal adiposity causes an impairment of testicular steroidogenesis that is directly linked to circulating adipokines; enhanced cytokine release from macrophage-infiltrated adipose tissue is pivotal to the pathogenesis of insulin resistance and atherosclerosis. Both MetS and T2D share with hypogonadism such a proinflammatory state.
For this reason we performed a randomized controlled trial on the effects of TRT on insulin resistance and circulating inflammatory markers in a cohort of middle-aged men with mild hypogonadism and MetS at first diagnosis, that were not taking medications known to influence the investigated outcomes. We established strict criteria for enrollment and used a physiological replacing therapy.
Given that testosterone replacement therapy (TRT) determines a reduction of body fat mass paralleled by an increase in fat free mass (6), and that TRT exerts an anti-inflammatory role inhibiting interleukins (IL), in particular the IL-6 gene (14), it remains to be established whether these independent effects also reflect in an improvement in insulin resistance.
- Conditions
- Hypogonadism, Metabolic Syndrome, Obesity, Erectile Dysfunction
- Being tested
- Testosterone, Placebo
- Keywords
- Adiponectin, Resistin, Adipocytes, Testosterone, Aging, HOMA-IR, Insulin, Hypogonadism, Metabolic Syndrome, Obesity, Erectile Dysfunction
- Medical subject headings
- Hypogonadism, Metabolic Syndrome, Obesity, Erectile Dysfunction, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TestosteroneDrug
Also called Androgel, Testogel
Testosterone transdermal gel 50 mg/day (5 gr)
PlaceboDrug
Placebo transdermal gel (5 gr)
| Study group | Role | What they receive |
|---|---|---|
| Testosterone gel | Experimental | Testosterone transdermal gel 50 mg/day Receives: Drug: Testosterone |
| Placebo gel | Placebo comparator | Placebo gel Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fat-Free Mass (kg)
Estimate of within subject absolute change in fat-free mass measured by DEXA (dual energy x-ray absorptiometry) at 3 months (90 days) interval during active or placebo treatment.
Measured: 3 months
Secondary outcomes (16)
Fat Mass (kg)
Estimate of within subject absolute change (Kg) in fat mass measured by DEXA at 3 months (90 days) interval during active or placebo treatment.
Measured: 3 months
HOMA-IR (homeostasis model assessment)- (insulin resistance)
Estimate of within subject absolute change in measure of insulin resistance homeostatic model HOMA-IR.
Measured: 3 months
CRP (C reactive protein)
C reactive protein (High sensitivity).
Measured: 3 months
Interleukins
Within subject absolute and percentage change in serum:
IL-1, IL-6, IL-10, IL-12, IL-2, IL-8, TNFa (tumor necrosis factor alpha)
Measured: 3 months
Adipokines
Estimate of within subject absolute change in serum:
ADIPONECTIN, LEPTIN, RESISTIN.
Measured: 3 months
Waist circumference
Waist circumference (cm)
Measured: 3 months
IIEF
International Index of Erectile Dysfunction
Measured: 3 months
Penile CDU (color Doppler ultrasound)
Penile Color-Doppler Ultrasonography of cavernosal arteries before and after active or placebo treatment.
Measured: 3 months
PSA (prostatic specific antigen)
PSA
Measured: 3 months
Hb, Htc
haemoglobin and haematocrit
Measured: 3 months
Fat-free mass
Measured: 6 months
Fat Mass
Measured: 6 months
HOMA-IR
Measured: 6 months
CRP
Measured: 6 months
Interleukins
Serum IL-1, IL-6, IL-10, IL-12, IL-2, IL-8, TNFa
Measured: 6 months
Adipokines
Serum ADIPONECTIN, LEPTIN, RESISTIN.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2010 (estimated)
- Study startJan 2004
- Primary completionOct 2014
- Study completionOct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for HypogonadismStudies of the same condition, open and under way.
- More trials run by University of Roma La SapienzaThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 82 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Roma La Sapienza
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Andrea M. Isidori, University of Roma La Sapienza
- Investigators
- Vincenzo Bonifacio, MD, PhD, Principal investigator, University of Roma La SapienzaAndrea M Isidori, MD, PhD, Study director, University of Roma La SapienzaAndrea Lenzi, MD, PhD, Study chair, University of Roma La Sapienza
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01123278
- Sponsor's protocol ID
- TestoMet05
- Acronym
- TERMSINFAT
- Status last verified
- Oct 2014
- First submitted
- 10 May 2010
- Last updated
- 28 Oct 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Isidori AM, Caprio M, Strollo F, Moretti C, Frajese G, Isidori A, Fabbri A. Leptin and androgens in male obesity: evidence for leptin contribution to reduced androgen levels. J Clin Endocrinol Metab. 1999 Oct;84(10):3673-80. doi: 10.1210/jcem.84.10.6082.
PubMed 10523013Aversa A, Isidori AM, Greco EA, Giannetta E, Gianfrilli D, Spera E, Fabbri A. Hormonal supplementation and erectile dysfunction. Eur Urol. 2004 May;45(5):535-8. doi: 10.1016/j.eururo.2004.01.005.
PubMed 15082192Isidori AM, Giannetta E, Pozza C, Bonifacio V, Isidori A. Androgens, cardiovascular disease and osteoporosis. J Endocrinol Invest. 2005;28(10 Suppl):73-9.
PubMed 16550728Isidori AM, Greco EA, Aversa A. Androgen deficiency and hormone-replacement therapy. BJU Int. 2005 Aug;96(2):212-6. doi: 10.1111/j.1464-410X.2005.05603.x. No abstract available.
PubMed 16001962Isidori AM, Giannetta E, Greco EA, Gianfrilli D, Bonifacio V, Isidori A, Lenzi A, Fabbri A. Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: a meta-analysis. Clin Endocrinol (Oxf). 2005 Sep;63(3):280-93. doi: 10.1111/j.1365-2265.2005.02339.x.
PubMed 16117815Isidori AM, Giannetta E, Gianfrilli D, Greco EA, Bonifacio V, Aversa A, Isidori A, Fabbri A, Lenzi A. Effects of testosterone on sexual function in men: results of a meta-analysis. Clin Endocrinol (Oxf). 2005 Oct;63(4):381-94. doi: 10.1111/j.1365-2265.2005.02350.x.
PubMed 16181230Isidori AM, Lenzi A. Testosterone replacement therapy: what we know is not yet enough. Mayo Clin Proc. 2007 Jan;82(1):11-3. doi: 10.4065/82.1.11. No abstract available.
PubMed 17285780Aversa A, Isidori AM, Spera G, Lenzi A, Fabbri A. Androgens improve cavernous vasodilation and response to sildenafil in patients with erectile dysfunction. Clin Endocrinol (Oxf). 2003 May;58(5):632-8. doi: 10.1046/j.1365-2265.2003.01764.x.
PubMed 12699447Aversa A, Isidori AM, De Martino MU, Caprio M, Fabbrini E, Rocchietti-March M, Frajese G, Fabbri A. Androgens and penile erection: evidence for a direct relationship between free testosterone and cavernous vasodilation in men with erectile dysfunction. Clin Endocrinol (Oxf). 2000 Oct;53(4):517-22. doi: 10.1046/j.1365-2265.2000.01118.x.
PubMed 11012578
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Testosterone Replacement in Metabolic Syndrome and Inflammation of Fat Tissue
- ClinicalTrials.gov ID
- NCT01123278
- Acronym / sponsor ID
- TERMSINFAT / TestoMet05
- Conditions
- Hypogonadism, Metabolic Syndrome, Obesity, Erectile Dysfunction
- Keywords
- Adiponectin, Resistin, Adipocytes, Testosterone, Aging, HOMA-IR, Insulin, Hypogonadism
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 82 participants (actual)
- Lead sponsor
- University of Roma La SapienzaUniversity, hospital or other
- Study start
- Jan 2004
- Primary completion
- Oct 2014 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 14 May 2010 (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.
Hypogonadism (HG) frequently complicates the Metabolic Syndrome (MetS), whether testosterone replacement (TRT) is beneficial has not been clearly ascertained. This study was designed to address the effects of TRT on insulin resistance, body composition and pro-inflammatory status in naïve patients with MetS and HG.
Detailed description
The features of Metabolic Syndrome (MetS) include abdominal obesity, atherogenic dyslipidemia, raised blood pressure, insulin resistance or glucose intolerance. These symptoms are also frequently found in hypogonadal men.
Adipose tissue and androgens in male obesity are reciprocally linked. Total and free testosterone (T) are decreased in proportion to the degree of body fatness while T regulates insulin sensitivity and body composition. As a consequence, hypoandrogenism carries an additional independent risk for cardiovascular and metabolic disorders. Men with type 2 diabetes mellitus (T2D) exhibit lowered T levels that are inversely correlated to HbA1c. In addition, abdominal adiposity causes an impairment of testicular steroidogenesis that is directly linked to circulating adipokines; enhanced cytokine release from macrophage-infiltrated adipose tissue is pivotal to the pathogenesis of insulin resistance and atherosclerosis. Both MetS and T2D share with hypogonadism such a proinflammatory state.
For this reason we performed a randomized controlled trial on the effects of TRT on insulin resistance and circulating inflammatory markers in a cohort of middle-aged men with mild hypogonadism and MetS at first diagnosis, that were not taking medications known to influence the investigated outcomes. We established strict criteria for enrollment and used a physiological replacing therapy.
Given that testosterone replacement therapy (TRT) determines a reduction of body fat mass paralleled by an increase in fat free mass (6), and that TRT exerts an anti-inflammatory role inhibiting interleukins (IL), in particular the IL-6 gene (14), it remains to be established whether these independent effects also reflect in an improvement in insulin resistance.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Testosterone gel | Experimental | Drug: TestosteroneTestosterone transdermal gel 50 mg/day |
| Placebo gel | Placebo comparator | Drug: PlaceboPlacebo gel |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- patients with Metabolic Syndrome according to ATPIII
- patients with mild hypogonadism (both testosterone evaluations between 6 and 11 nmol/L)
- patients naïve to hypoglycemic therapies
Key exclusion criteria (4 listed)
- patients on hypoglycemic medications
- patients with severe hypogonadism (<5 nmol/L)
- patients with borderline T values hypogonadism (>11 nmol/L)
- patients with contraindication to testosterone therapy: prostate cancer, PSA>4 ng/ml, severe hepatic or renal insufficiency, Hb>17, Htc>52%, severe urinary retention
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: Androgel, TestogelTestosterone transdermal gel 50 mg/day (5 gr) | Drug | Testosterone gel |
| PlaceboPlacebo transdermal gel (5 gr) | Drug | Placebo gel |
Primary outcome
Fat-Free Mass (kg)
Time frame: 3 months
Estimate of within subject absolute change in fat-free mass measured by DEXA (dual energy x-ray absorptiometry) at 3 months (90 days) interval during active or placebo treatment.
16 secondary outcomes
Fat Mass (kg)
Time frame: 3 months
HOMA-IR (homeostasis model assessment)- (insulin resistance)
Time frame: 3 months
CRP (C reactive protein)
Time frame: 3 months
Interleukins
Time frame: 3 months
Adipokines
Time frame: 3 months
Waist circumference
Time frame: 3 months
IIEF
Time frame: 3 months
Penile CDU (color Doppler ultrasound)
Time frame: 3 months
PSA (prostatic specific antigen)
Time frame: 3 months
Hb, Htc
Time frame: 3 months
Fat-free mass
Time frame: 6 months
Fat Mass
Time frame: 6 months
HOMA-IR
Time frame: 6 months
CRP
Time frame: 6 months
Interleukins
Time frame: 6 months
Adipokines
Time frame: 6 months
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 28 Oct 2014.
- Background: PubMed 10523013Isidori AM, Caprio M, Strollo F, Moretti C, Frajese G, Isidori A, Fabbri A. Leptin and androgens in male obesity: evidence for leptin contribution to reduced androgen levels. J Clin Endocrinol Metab. 1999 Oct;84(10):3673-80. doi: 10.1210/jcem.84.10.6082.
- Background: PubMed 15082192Aversa A, Isidori AM, Greco EA, Giannetta E, Gianfrilli D, Spera E, Fabbri A. Hormonal supplementation and erectile dysfunction. Eur Urol. 2004 May;45(5):535-8. doi: 10.1016/j.eururo.2004.01.005.
- Background: PubMed 16550728Isidori AM, Giannetta E, Pozza C, Bonifacio V, Isidori A. Androgens, cardiovascular disease and osteoporosis. J Endocrinol Invest. 2005;28(10 Suppl):73-9.
- Background: PubMed 16001962Isidori AM, Greco EA, Aversa A. Androgen deficiency and hormone-replacement therapy. BJU Int. 2005 Aug;96(2):212-6. doi: 10.1111/j.1464-410X.2005.05603.x. No abstract available.
- Background: PubMed 16117815Isidori AM, Giannetta E, Greco EA, Gianfrilli D, Bonifacio V, Isidori A, Lenzi A, Fabbri A. Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: a meta-analysis. Clin Endocrinol (Oxf). 2005 Sep;63(3):280-93. doi: 10.1111/j.1365-2265.2005.02339.x.
- Background: PubMed 16181230Isidori AM, Giannetta E, Gianfrilli D, Greco EA, Bonifacio V, Aversa A, Isidori A, Fabbri A, Lenzi A. Effects of testosterone on sexual function in men: results of a meta-analysis. Clin Endocrinol (Oxf). 2005 Oct;63(4):381-94. doi: 10.1111/j.1365-2265.2005.02350.x.
- Background: PubMed 17285780Isidori AM, Lenzi A. Testosterone replacement therapy: what we know is not yet enough. Mayo Clin Proc. 2007 Jan;82(1):11-3. doi: 10.4065/82.1.11. No abstract available.
- Background: PubMed 12699447Aversa A, Isidori AM, Spera G, Lenzi A, Fabbri A. Androgens improve cavernous vasodilation and response to sildenafil in patients with erectile dysfunction. Clin Endocrinol (Oxf). 2003 May;58(5):632-8. doi: 10.1046/j.1365-2265.2003.01764.x.
- Background: PubMed 11012578Aversa A, Isidori AM, De Martino MU, Caprio M, Fabbrini E, Rocchietti-March M, Frajese G, Fabbri A. Androgens and penile erection: evidence for a direct relationship between free testosterone and cavernous vasodilation in men with erectile dysfunction. Clin Endocrinol (Oxf). 2000 Oct;53(4):517-22. doi: 10.1046/j.1365-2265.2000.01118.x.
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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.
Vincenzo Bonifacio, MD, PhD principal investigator
University of Roma La Sapienza
Andrea M Isidori, MD, PhD study director
University of Roma La Sapienza
Andrea Lenzi, MD, PhD study chair
University of Roma La Sapienza
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Testosterone in people with Hypogonadism and Metabolic Syndrome, run by University of Roma La Sapienza at 2 sites in Italy.
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 4 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 28 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. 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. Some participants in this study may receive a placebo. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
Fat-Free Mass (kg) (time frame: 3 months). 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 NCT01123278, which also lists 9 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 28 Oct 2014.