Effect of Hypogonadotrophic Hypogonadism and Treatment With Testosterone on Insulin Sensitivity, Inflammation, Body Composition and Sexual Function in Obese and Type 2 Diabetic Men
| City: |
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Williamsville |
| State: |
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New York |
| Zip Code: |
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14221 |
| Conditions: |
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Hypogonadism |
| Purpose: |
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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.
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| Study Summary: |
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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 each arm. Each arm will have 60 men
with HH and 60 men with 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 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. For baseline comparisons, 60 men with normal testosterone
concentrations will also be needed in each arm. Thus there will be 120 men in each arm and a
total of 240 subjects in the study.
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| Criteria: |
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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.
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| NCT ID: |
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NCT01127659 |
| Primary Contact: |
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Principal Investigator
Paresh Dandona, MBBS
SUNY at Buffalo
Paresh Dandona, MBBS
Phone: 716-626-7998
Email: pdandona@kaleidahealth.org
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| Backup Contact: |
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Email: jhejna@kaleidahealth.org
Jeanne Hejna, LPN
Phone: 716-626-7998
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| Location Contact: |
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Williamsville, New York 14221
United States
Jeanne Hejna, LPN
Phone: 716-626-7998
Email: jhejna@kaleidahealth.org
Site Status: Recruiting |
| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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June 18, 2013 |
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