Investigator Initiated Study of the Effects of Androgen Therapy on Carbohydrate and Lipid Metabolism In Elderly Men
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Change in Total Mass and Regional Adipose Adiposiy
研究概览
简要总结
A. HYPOTHESES: In older men low testosterone levels, abdominal obesity and elevated fasting insulin who are at risk for the cardiovascular complications such as heart attack and stroke.
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Supplemental testosterone will decrease abdominal adipose tissue and hepatic fat) and appendicular fat and intramyocellular lipid in peripheral muscles (IMCL).
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Supplemental testosterone will improve insulin sensitivity by:
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Decreasing hepatic glucose output (HGO), a measure of central insulin resistance
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increasing peipheral glucose disposal (Rd), a measure of periperal insuln sensiivity
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. Improving peripheral glucose disposal (Rd) by reducing IMCL
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Increasing appendicular skeletal muscle mass
B. OBJECTIVES:
- Primary Objective: To determine the effects of supplemental testosterone to achieve testosterone levels in the upper normal physiologic range on central adipose tissue (abdominal and hepatic fat) and peripheral skeletal muscle fat (appendicular fat and IMCL).
- Secondary Objectives: To determine the effects of supplemental testosterone to achieve testosterone levels in the upper normal physiologic range:on central insulin sensitivity ( hepatic glucose output ([HGO]) and peripheral insulin sensitivity (glucose disposal (Rd)
Results of this study will provide greater understanding whether androgen therapy enhances insulin sensitivity by decreasing HGO, improving peripheral Rd and if these desired effects are achieved, whether they are due to reductions in abdominal fat or liver lipid, IMCL or effects of augmenting muscle mass per se.
Results will generate hypotheses to investigate cellular and molecular mechanisms of androgen effects in persons at risk for the Metabolic Syndrome.
详细描述
Study Design: This is an investigator-initiated open label, study to investigate the effects of supplemental testosterone (gel formulation) to increase testosterone levels to the upper normal range in 12 older hypogonadal (testosterone levels less than 300 ng/dL) men with abdominal obesity and elevated fasting insulin levels. Subjects will be assigned to receive 10 g of transdermal testosterone (Androgel) every morning to achieve levels in the upper normal physiologic range (similar to men in the 3rd and 4th decades) for 20 weeks.
- For the primary objective, regional adipose tissue, namely DEXA measures of abdominal and appendicular fat mass and hepatic fat, and IMCL will be quantified by 1H-spectroscopy at baseline (study week 0) and at study week 20 (completion of study therapy).
- For the secondary objective, insulin sensitivity (peripheral Rd, hepatic glucose output [HGO]) and hepatic gluconeogenesis will be measured directly during a two stage hyperinsulinemic euglycemic clamp at baseline and study week 20.
- Indirect markers of lipid (adiponectin, ApoB 100) and carbohydrate metabolism (Fasting blood sugar, HOMA-IR) at study week 10, and study week 20.
All components of the study will be conducted in the USC NIH-funded (NCRR), General Clinical Research Center.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
No masking. This was an open label (un-blinded)
入排标准
- 年龄范围
- 60 Years 至 90 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Entry Criteria:
- •Men > 60 years of age
- •Total testosterone < 300 ng/dL
- •Waist circumference >102 cm
- •Fasting insulin level > 18 U/L
排除标准
- •PSA > 4.1, symptoms of obstructive uropathy (AUA score > 14), unexplained prostate nodule or gland firmness
- •Hematocrit > 50%
- •Malignancy other than cutaneous cancers
- •Sleep apnea requiring CPAP
- •History of myocardial infarction, angina or stroke within the previous 6 months
- •Clinical diagnosis of diabetes or FPG > 126 mg/dL
- •Hypothyroidism not controlled to euthyroid levels with medication for at least 3 months
- •LDL-C >160 mg/dL
- •Transaminases > 1.5X ULN
- •Systemic anticoagulation with warfarin
- •Active progressive resistance training
- •Dieting for weight loss
- •Active inflammatory condition (e.g. rheumatoid arthritis)
- •Use of any anabolic agent (e.g. growth hormone, testosterone precursor, anabolic steroid)or cytokine therapy in the proceeding 12 months
研究组 & 干预措施
Single arm
Open label treatment without masking with each participant serving as his own control. Measurements are compared before and after treatment.
干预措施: Topical testosterone gel 10 g/day (Drug)
结局指标
主要结局
Change in Total Mass and Regional Adipose Adiposiy
时间窗: Baseline to 20 weeks
Change in total body mass, total fat mass, trunk fat, and extremity fat
Intramyocellular Lipid (IMCL)
时间窗: Baseline to week 20
IMCL is quantified by MR spectroscopy of the anterior tibialis muscle of the leg. The value is adjusted for creatine and reported as a ratio
Change in Hepatic Lipid
时间窗: Baseline to week 20
Amount of liver fat is highly predictive of insulin resistance. Hepatic fat is measured by MR spectroscopy and adjusted for H2O and results are reported as ratio of these two.
次要结局
- Change in HOMA-IR(Baseline to week 20)
- Change in Total and Regional Carbohydrate Metabolism During a 2-hr Hyperinsulinemic Euglycemic Clamp and [6,6-2H2] Glucose Studies (Peripheral Glucose Disposal [Rd],Hepatic Glucose Output [HGO])(Baseline and 20 weeks)
- Change in Skeletal Muscle Mass by DEXA(Baselne to 20 weeks)
- Plasma Lipids(Baseline to week 20)
- Change in Percentage of Total Body Fat(Baseline and 20 weeks)
- Change in Plasma Free Fatty Acids During Glucose Clamp(Baseline to 20 weeks)
- Change in Basal FFAs in Plasma(Baseline to week 20)
研究者
Fred Sattler, MD
Professor
University of Southern California