Testosterone Replacement in Men With Diabetes and Obesity

• Sponsor: University at Buffalo (Other)
• Overall Status: Completed
• CT.gov ID: NCT01127659
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
• Enrollment: 144
• Location: 1
• Arms: 6
• Duration (Months): 58
• Patients Per Site Per Month: 2.5

Study Details

Study Description

Brief 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. 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.

Condition or Disease	Intervention/Treatment	Phase
Hypogonadism	Drug: testosterone; Drug: placebo	Phase 4

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

• Study Type: Interventional
• Actual Enrollment: 144 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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
• Study Start Date: May 1, 2010
• Actual Primary Completion Date: Mar 1, 2015
• Actual Study Completion Date: Mar 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: diabetes with HH-active Subjects with diabetes and hypogonadotropic hypogonadism. They will be randomized to testosterone intervention.	Drug: testosterone; intramuscular every 2 weeks
No Intervention: diabetes with normal testosterone Eugonadal subjects with diabetes. They will not be treated
Active Comparator: obese with HH-active Obese non-diabetic men hypogonadotropic hypogonadism. They will be randomized to testosterone intervention.	Drug: testosterone; intramuscular every 2 weeks
No Intervention: obese with normal testosterone Eugonadal non-diabetic obese subjects. They will not be treated
Placebo Comparator: Diabetes with HH-placebo Subjects with diabetes and hypogonadotropic hypogonadism. They will be randomized to placebo.	Drug: placebo; saline intramuscular every 2 weeks
Placebo Comparator: Obese with HH-placebo Obese non-diabetic men hypogonadotropic hypogonadism. They will be randomized to placebo.	Drug: placebo; saline intramuscular every 2 weeks

Outcome Measures

Primary Outcome Measures

1. Insulin Sensitivity [6 months]

   measured by HE clamps (baseline and 6 mths)

Secondary Outcome Measures

1. Body Composition [6 months]

2. Inflammation [6 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years to 65 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• T2D arm: Males with age 30-65 years

• Obese non-diabetic arm: Obese non-diabetic males with age 30-65 years

Exclusion Criteria:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	115 Flint Road	Williamsville	New York	United States	14221

Sponsors and Collaborators

• University at Buffalo
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Paresh Dandona, MBBS, SUNY at Buffalo

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Paresh Dandona, MD, University at Buffalo
• ClinicalTrials.gov Identifier: NCT01127659
• Other Study ID Numbers: NIH testosterone grant; R01DK075877
• First Posted: May 21, 2010
• Last Update Posted: Apr 12, 2017
• Last Verified: Mar 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Paresh Dandona, MD, University at Buffalo: diabetes; hypogonadism; obesity; testosterone; insulin sensitivity; inflammation
• Additional relevant MeSH terms: Hypogonadism; Testosterone

Study Results

Participant Flow

Arm/Group Title	Diabetes With HH: Testosterone	Diabetes With HH: Placebo	Obese Testosterone	Obese Placebo	Eugonadal Diabetes	Eugonadal Obese
Arm/Group Description	active drug diabetes arm testosterone: intramuscular every 2 weeks	placebo diabetes arm placebo: saline intramuscular every 2 weeks	active drug obese arm testosterone: intramuscular every 2 weeks	placebo obese arm placebo: saline intramuscular every 2 weeks	no intervention	no intervention
Period Title: Overall Study
STARTED	22	22	12	10	50	21
COMPLETED	20	14	10	6	50	21
NOT COMPLETED	2	8	2	4	0	0

Baseline Characteristics

Arm/Group Title	Diabetes With HH: Testosterone	Obese With HH: Testosterone	Obese With HH: Placebo	Diabetes With HH: Placebo	Eugonadal Diabetes	Eugonadal Obese	Total
Arm/Group Description	active drug diabetes hypogonadal arm testosterone: intramuscular every 2 weeks	active drug obese hypogonadal arm testosterone: intramuscular every 2 weeks	placebo obese hypogonadal arm placebo: saline intramuscular every 2 weeks	placebo diabetes hypogonadal arm placebo: saline intramuscular every 2 weeks	diabetic men with normal testosterone	obese non-diabetic men with normal testosterone	Total of all reporting groups
Overall Participants	22	12	10	22	50	21	137
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	22 100%	12 100%	10 100%	22 100%	50 100%	21 100%	137 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54 (7)	46 (9)	53 (7)	54 (9)	52 (9)	50 (8)	52 (8)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Male	22 100%	12 100%	10 100%	22 100%	50 100%	21 100%	137 100%
Region of Enrollment (participants) [Number]
United States	22 100%	12 100%	10 100%	22 100%	50 100%	21 100%	137 100%

Outcome Measures

1. Primary Outcome

Title	Insulin Sensitivity
Description	measured by HE clamps (baseline and 6 mths)
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Glucose infusion rate in HE clamps was measured

Arm/Group Title	Diabetes With HH: Testosterone	Diabetes With HH: Placebo	Obese With HH: Testosterone	Obese With HH: Placebo	Eugonadal Diabetes	Eugonadal Obese
Arm/Group Description	active drug diabetes hypogonadal arm testosterone: intramuscular every 2 weeks Glucose infusion rate: 6.5+/-4.0 mg/kg fat-free mass/min	placebo diabetes hypogonadal arm placebo: saline intramuscular every 2 weeks	active drug obese hypogonadal arm testosterone: intramuscular every 2 weeks	placebo obese hypogonadal arm placebo: saline intramuscular every 2 weeks	diabetic men with normal testosterone Glucose infusion rate: 10.29+/-5.55 mg/kg fat-free mass/min	obese non-diabetic men with normal testosterone
Measure Participants	20	14	10	6	50	21
baseline	6.66 (4.36)	5.12 (2.79)	11.37 (8.83)	12.93 (5.16)	10.29 (5.55)	12.30 (5.96)
6 months	8.73 (4.27)	5.06 (3.62)	12.96 (7.11)	14.57 (1.71)	NA (NA)	NA (NA)

2. Secondary Outcome

Title	Body Composition
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Inflammation
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Diabetes With HH: Testosterone		Diabetes With HH: Placebo		Obese With HH: Testosterone		Obese With HH: Placebo		Eugonadal Diabetes		Eugonadal Obese
Arm/Group Description	active drug diabetes hypogonadal arm testosterone: intramuscular every 2 weeks		placebo diabetes hypogonadal arm placebo: saline intramuscular every 2 weeks		active drug obese hypogonadal arm testosterone: intramuscular every 2 weeks		placebo obese hypogonadal arm placebo: saline intramuscular every 2 weeks		diabetic men with normal testosterone		obese non-diabetic men with normal testosterone
All Cause Mortality
	Diabetes With HH: Testosterone		Diabetes With HH: Placebo		Obese With HH: Testosterone		Obese With HH: Placebo		Eugonadal Diabetes		Eugonadal Obese
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Diabetes With HH: Testosterone		Diabetes With HH: Placebo		Obese With HH: Testosterone		Obese With HH: Placebo		Eugonadal Diabetes		Eugonadal Obese
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/22 (0%)		0/12 (0%)		0/10 (0%)		0/50 (0%)		0/21 (0%)
Other (Not Including Serious) Adverse Events
	Diabetes With HH: Testosterone		Diabetes With HH: Placebo		Obese With HH: Testosterone		Obese With HH: Placebo		Eugonadal Diabetes		Eugonadal Obese
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/22 (0%)		0/12 (0%)		0/10 (0%)		0/50 (0%)		0/21 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.