HypogonadismPhase 4NCT01127659
Testosterone Replacement in Men With Diabetes and Obesity
A Phase 4 study testing testosterone in people with Hypogonadism, run by University at Buffalo at 1 site in United States.
Trial summary
The purpose of this study is to examine the effect of having testosterone deficiency in men with diabetes and with obesity. The study will also evaluate the effect of testosterone therapy. Read more about this study
- Who is it for?
- Ages 30 to 65 years, men only
- Conditions the study is for
- Hypogonadism
- What is being tested?
- testosterone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 137 participants
- Where
- 1 siteUnited States
- Study dates
- May 2010to Nov 2015
- Phase
- Phase 4
- 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 30 to 65 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- T2D arm: Males with age 30-65 years
- Obese non-diabetic arm: Obese non-diabetic males with age 30-65 years
Who cannot join
- 1)Coronary event or procedure(myocardial infarction, unstable angina, coronary artery bypass, surgery or coronary angioplasty) in the previous twelve weeks; 2) PSA > 4ng/ml; 3)Hemoglobin A1c > 8%; 4)h/o prostate carcinoma; 5)Hepatic disease (transaminase > 3 times normal) or cirrhosis; 6)Renal impairment (defined as GFR<30); 7)HIV or Hepatitis C positive status; 9)Participation in any other concurrent clinical trial; 10)Any other life-threatening, non-cardiac disease; 11)Use of over the counter health supplements which contain androgens; 12)Use of an investigational agent or therapeutic regimen within 30 days of study; 13)prostate nodule or severe enlargement on digital rectal examination; 14)Use of testosterone currently or in the past 4 months; 15)Hematocrit > 50%; 16)History of untreated severe obstructive sleep apnea(defined as apnea-hypopnea index ≥30); 17)symptoms suggestive of severe BPH; 18)Congestive heart failure, class III or IV; 20)Known to have anemia secondary to iron, B12 or folic acid deficiency; 21)bone marrow disorder such as myelodysplasia or aplastic anemia; 22) currently suffering from symptomatic depression, with or without treatment; 23) history of severe depression in the past which needed hospitalization; 24)currently suffering from foot ulcer, significant periodontal disease or any other chronic infectious condition; 25)planning to have children. 26) Subjects on testosterone or with testosterone replacement in the past 4 months will be excluded.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Hypogonadotrophic Hypogonadism and Treatment With Testosterone on Insulin Sensitivity, Inflammation, Body Composition and Sexual Function in Obese and Type 2 Diabetic Men
The purpose of this study is to examine the effect of having testosterone deficiency in men with diabetes and with obesity. The study will also evaluate the effect of testosterone therapy. This will be done by comparing the changes in several body response indicators following treatment with testosterone in diabetic or obese-non diabetic men with low testosterone levels and comparing them to diabetic or obese-non diabetic men with low testosterone who are not treated with testosterone.
Read the detailed description
Hypogonadotropic hypogonadism (HH) occurs in approximately one-third of obese and type 2 diabetic men. Considering that there are 24 million diabetic and 100 million obese people, of which half are males, obesity and type 2 diabetes potentially constitute the major cause of hypogonadism in the population. We hypothesize that 1) HH in obese and type 2 diabetic men is associated with decreased insulin sensitivity, increased fat tissue mass, decreased lean body mass, increased inflammatory and oxidative stress, impaired sexual function and depressed mood as compared to diabetic and obese men with normal testosterone concentrations; and that 2) testosterone replacement for 24 weeks in men with HH leads to an improvement in these parameters. Our proposed study would be the first prospective, randomized trial to comprehensively evaluate the effect of HH on insulin sensitivity, body composition, inflammatory and oxidative indices in obese and type 2 diabetic subjects and the effect of six months of T replacement on these parameters. The study will have 2 arms (obese and type 2 diabetic arm) with 120 subjects in Diabetes arm and 80 subjects in obese arm. Half of men in each arm will have HH and half men will have normal testosterone concentrations(eugonadal men). Insulin sensitivity will be assessed by hyperinsulinemic-euglycemic clamps. Subcutaneous fat mass and lean body mass will be measured by DEXA and intra-abdominal (visceral) fat mass by MRI. All subjects will undergo hyperinsulinemic-euglycemic clamp, MRI, DEXA and give blood and urine samples (for measurement of inflammatory and oxidative stress) at baseline. Men with HH will then be randomized to receive testosterone or placebo gel for a total of 24 weeks. These men will undergo hyperinsulinemic-euglycemic clamps and give blood and urine samples for inflammation and oxidative stress at 4 weeks and 24 weeks. MRI and DEXA examinations will be carried out at 24 weeks again in men with HH. The primary endpoint of the study is to define a difference in whole body glucose uptake during hyperinsulinemic-euglycemic clamps between hypogonadal and eugonadal diabetes patients at baseline and an increase in glucose uptake in HH subjects after treatment with testosterone for 24 weeks. 30 subjects per group(testosterone and placebo gel each) will provide adequate power (0.8) to detect a significant difference of 10% in whole body glucose uptake. Therefore there will be 60 men with HH in each arm in diabetes group. For baseline comparisons, 60 men with normal testosterone concentrations will also be needed in each arm. We will recruit 40 obese patients in each arm. Thus there will be 120 diabetic men and 80 obese men in the study.
- Conditions
- Hypogonadism
- Being tested
- testosterone, placebo
- Keywords
- diabetes, hypogonadism, obesity, testosterone, insulin sensitivity, inflammation
- Medical subject headings
- Hypogonadism, Diabetes Mellitus, Obesity, Insulin Resistance, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
testosteroneDrug
intramuscular every 2 weeks
placeboDrug
saline intramuscular every 2 weeks
| Study group | Role | What they receive |
|---|---|---|
| diabetes with HH-active | Active comparator | Subjects with diabetes and hypogonadotropic hypogonadism. They will be randomized to testosterone intervention. Receives: Drug: testosterone |
| diabetes with normal testosterone | No intervention | Eugonadal subjects with diabetes. They will not be treated |
| obese with HH-active | Active comparator | Obese non-diabetic men hypogonadotropic hypogonadism. They will be randomized to testosterone intervention. Receives: Drug: testosterone |
| obese with normal testosterone | No intervention | Eugonadal non-diabetic obese subjects. They will not be treated |
| Diabetes with HH-placebo | Placebo comparator | Subjects with diabetes and hypogonadotropic hypogonadism. They will be randomized to placebo. Receives: Drug: placebo |
| Obese with HH-placebo | Placebo comparator | Obese non-diabetic men hypogonadotropic hypogonadism. They will be randomized to placebo. Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insulin Sensitivity
measured by HE clamps (baseline and 6 mths)
Measured: baseline to 6 months
Secondary outcomes (1)
Body Composition
Body composition using Total body fat mass (kg)
Measured: baseline to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2010 (estimated)
- Study startMay 2010
- Primary completionMar 2015
- Study completionNov 2015
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 (3)Papers the sponsor has linked to this study.
- Other trials for HypogonadismStudies 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 137 participants (actual)
Sponsor and investigators
- Lead sponsor
- University at Buffalo
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Paresh Dandona, University at Buffalo
- Investigators
- Paresh Dandona, MBBS, Principal investigator, SUNY at Buffalo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01127659
- Sponsor's protocol ID
- NIH testosterone grant
- Other IDs
- R01DK075877
- Status last verified
- Oct 2022
- First submitted
- 20 May 2010
- Last updated
- 29 Nov 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Ghanim H, Dhindsa S, Batra M, Green K, Abuaysheh S, Kuhadiya ND, Makdissi A, Chaudhuri A, Sandhu S, Dandona P. Testosterone Increases the Expression and Phosphorylation of AMP Kinase alpha in Men With Hypogonadism and Type 2 Diabetes. J Clin Endocrinol Metab. 2020 Apr 1;105(4):1169-75. doi: 10.1210/clinem/dgz288.
PubMed 31858126Ghanim H, Dhindsa S, Batra M, Green K, Abuaysheh S, Kuhadiya ND, Makdissi A, Chaudhuri A, Dandona P. Effect of Testosterone on FGF2, MRF4, and Myostatin in Hypogonadotropic Hypogonadism: Relevance to Muscle Growth. J Clin Endocrinol Metab. 2019 Jun 1;104(6):2094-2102. doi: 10.1210/jc.2018-01832.
PubMed 30629183Dhindsa S, Ghanim H, Batra M, Kuhadiya ND, Abuaysheh S, Sandhu S, Green K, Makdissi A, Hejna J, Chaudhuri A, Punyanitya M, Dandona P. Insulin Resistance and Inflammation in Hypogonadotropic Hypogonadism and Their Reduction After Testosterone Replacement in Men With Type 2 Diabetes. Diabetes Care. 2016 Jan;39(1):82-91. doi: 10.2337/dc15-1518. Epub 2015 Nov 29.
PubMed 26622051
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Hypogonadotrophic Hypogonadism and Treatment With Testosterone on Insulin Sensitivity, Inflammation, Body Composition and Sexual Function in Obese and Type 2 Diabetic Men
- ClinicalTrials.gov ID
- NCT01127659
- Acronym / sponsor ID
- NIH testosterone grant
- Conditions
- Hypogonadism
- Keywords
- diabetes, hypogonadism, obesity, testosterone, insulin sensitivity, inflammation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 137 participants (actual)
- Lead sponsor
- University at BuffaloUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- May 2010
- Primary completion
- Mar 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 21 May 2010 (estimated)
- Results
- Posted 7 Mar 2017
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 examine the effect of having testosterone deficiency in men with diabetes and with obesity. The study will also evaluate the effect of testosterone therapy. This will be done by comparing the changes in several body response indicators following treatment with testosterone in diabetic or obese-non diabetic men with low testosterone levels and comparing them to diabetic or obese-non diabetic men with low testosterone who are not treated with testosterone.
Detailed description
Hypogonadotropic hypogonadism (HH) occurs in approximately one-third of obese and type 2 diabetic men. Considering that there are 24 million diabetic and 100 million obese people, of which half are males, obesity and type 2 diabetes potentially constitute the major cause of hypogonadism in the population. We hypothesize that 1) HH in obese and type 2 diabetic men is associated with decreased insulin sensitivity, increased fat tissue mass, decreased lean body mass, increased inflammatory and oxidative stress, impaired sexual function and depressed mood as compared to diabetic and obese men with normal testosterone concentrations; and that 2) testosterone replacement for 24 weeks in men with HH leads to an improvement in these parameters. Our proposed study would be the first prospective, randomized trial to comprehensively evaluate the effect of HH on insulin sensitivity, body composition, inflammatory and oxidative indices in obese and type 2 diabetic subjects and the effect of six months of T replacement on these parameters. The study will have 2 arms (obese and type 2 diabetic arm) with 120 subjects in Diabetes arm and 80 subjects in obese arm. Half of men in each arm will have HH and half men will have normal testosterone concentrations(eugonadal men). Insulin sensitivity will be assessed by hyperinsulinemic-euglycemic clamps. Subcutaneous fat mass and lean body mass will be measured by DEXA and intra-abdominal (visceral) fat mass by MRI. All subjects will undergo hyperinsulinemic-euglycemic clamp, MRI, DEXA and give blood and urine samples (for measurement of inflammatory and oxidative stress) at baseline. Men with HH will then be randomized to receive testosterone or placebo gel for a total of 24 weeks. These men will undergo hyperinsulinemic-euglycemic clamps and give blood and urine samples for inflammation and oxidative stress at 4 weeks and 24 weeks. MRI and DEXA examinations will be carried out at 24 weeks again in men with HH. The primary endpoint of the study is to define a difference in whole body glucose uptake during hyperinsulinemic-euglycemic clamps between hypogonadal and eugonadal diabetes patients at baseline and an increase in glucose uptake in HH subjects after treatment with testosterone for 24 weeks. 30 subjects per group(testosterone and placebo gel each) will provide adequate power (0.8) to detect a significant difference of 10% in whole body glucose uptake. Therefore there will be 60 men with HH in each arm in diabetes group. For baseline comparisons, 60 men with normal testosterone concentrations will also be needed in each arm. We will recruit 40 obese patients in each arm. Thus there will be 120 diabetic men and 80 obese men in the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| diabetes with HH-active | Active comparator | Drug: testosteroneSubjects with diabetes and hypogonadotropic hypogonadism. They will be randomized to testosterone intervention. |
| diabetes with normal testosterone | No intervention | –Eugonadal subjects with diabetes. They will not be treated |
| obese with HH-active | Active comparator | Drug: testosteroneObese non-diabetic men hypogonadotropic hypogonadism. They will be randomized to testosterone intervention. |
| obese with normal testosterone | No intervention | –Eugonadal non-diabetic obese subjects. They will not be treated |
| Diabetes with HH-placebo | Placebo comparator | Drug: placeboSubjects with diabetes and hypogonadotropic hypogonadism. They will be randomized to placebo. |
| Obese with HH-placebo | Placebo comparator | Drug: placeboObese non-diabetic men hypogonadotropic hypogonadism. They will be randomized to placebo. |
Who may qualify
- Ages
- 30 to 65 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- T2D arm: Males with age 30-65 years
- Obese non-diabetic arm: Obese non-diabetic males with age 30-65 years
Key exclusion criteria (1 listed)
- 1)Coronary event or procedure(myocardial infarction, unstable angina, coronary artery bypass, surgery or coronary angioplasty) in the previous twelve weeks; 2) PSA > 4ng/ml; 3)Hemoglobin A1c > 8%; 4)h/o prostate carcinoma; 5)Hepatic disease (transaminase > 3 times normal) or cirrhosis; 6)Renal impairment (defined as GFR<30); 7)HIV or Hepatitis C positive status; 9)Participation in any other concurrent clinical trial; 10)Any other life-threatening, non-cardiac disease; 11)Use of over the counter health supplements which contain androgens; 12)Use of an investigational agent or therapeutic regimen within 30 days of study; 13)prostate nodule or severe enlargement on digital rectal examination; 14)Use of testosterone currently or in the past 4 months; 15)Hematocrit > 50%; 16)History of untreated severe obstructive sleep apnea(defined as apnea-hypopnea index ≥30); 17)symptoms suggestive of severe BPH; 18)Congestive heart failure, class III or IV; 20)Known to have anemia secondary to iron, B12 or folic acid deficiency; 21)bone marrow disorder such as myelodysplasia or aplastic anemia; 22) currently suffering from symptomatic depression, with or without treatment; 23) history of severe depression in the past which needed hospitalization; 24)currently suffering from foot ulcer, significant periodontal disease or any other chronic infectious condition; 25)planning to have children. 26) Subjects on testosterone or with testosterone replacement in the past 4 months will be excluded.
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 |
|---|---|---|
| testosteroneintramuscular every 2 weeks | Drug | diabetes with HH-active, obese with HH-active |
| placebosaline intramuscular every 2 weeks | Drug | Diabetes with HH-placebo, Obese with HH-placebo |
Primary outcome
Insulin Sensitivity
Time frame: baseline to 6 months
measured by HE clamps (baseline and 6 mths)
1 secondary outcome
Body Composition
Time frame: baseline to 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31858126Ghanim H, Dhindsa S, Batra M, Green K, Abuaysheh S, Kuhadiya ND, Makdissi A, Chaudhuri A, Sandhu S, Dandona P. Testosterone Increases the Expression and Phosphorylation of AMP Kinase alpha in Men With Hypogonadism and Type 2 Diabetes. J Clin Endocrinol Metab. 2020 Apr 1;105(4):1169-75. doi: 10.1210/clinem/dgz288.
- Derived from this study: PubMed 30629183Ghanim H, Dhindsa S, Batra M, Green K, Abuaysheh S, Kuhadiya ND, Makdissi A, Chaudhuri A, Dandona P. Effect of Testosterone on FGF2, MRF4, and Myostatin in Hypogonadotropic Hypogonadism: Relevance to Muscle Growth. J Clin Endocrinol Metab. 2019 Jun 1;104(6):2094-2102. doi: 10.1210/jc.2018-01832.
- Derived from this study: PubMed 26622051Dhindsa S, Ghanim H, Batra M, Kuhadiya ND, Abuaysheh S, Sandhu S, Green K, Makdissi A, Hejna J, Chaudhuri A, Punyanitya M, Dandona P. Insulin Resistance and Inflammation in Hypogonadotropic Hypogonadism and Their Reduction After Testosterone Replacement in Men With Type 2 Diabetes. Diabetes Care. 2016 Jan;39(1):82-91. doi: 10.2337/dc15-1518. Epub 2015 Nov 29.
- Individual participant dataSharing planned: No
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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.
Paresh Dandona, MBBS principal investigator
SUNY at Buffalo
1 site 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, run by University at Buffalo 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 2 inclusion and 1 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 29 Nov 2022. 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. 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?
Yes. Results are posted in the registry (first posted 7 Mar 2017). 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?
Insulin Sensitivity (time frame: baseline to 6 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 NCT01127659, which also lists 3 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 29 Nov 2022.