Insulin Sensitivity in Men With the Metabolic Syndrome
Effect of Increasing Testosterone on Insulin Sensitivity in Men With the Metabolic Syndrome
The metabolic syndrome is a medical condition defined by high levels of cholesterol in the blood, high blood pressure, central obesity (gain in fat around the region of the stomach), and insulin resistance (body responds less well to insulin).
This state of impaired insulin resistance can lead to type 2 diabetes mellitus, which is one of the most common metabolic disorders in the U.S. Numerous studies have shown an inverse relationship between insulin resistance and testosterone levels in men, however, causality has not been established.
This protocol investigates the role of testosterone in modulating insulin sensitivity in insulin resistant states such as the metabolic syndrome.
The hypothesis is that testosterone administration will improve insulin sensitivity.
調査の概要
状態
一時停止
詳細な説明
This protocol will address the impact of three months of testosterone (T) therapy on all components of the metabolic syndrome and the mechanism underlying changes in insulin sensitivity by analyzing changes in body composition, and detailed studies of fat metabolism and skeletal muscle. In addition, this protocol will address the role of estradiol (E2) in mediating the effect of testosterone on insulin sensitivity.
Seventy-two subjects will be enrolled. Study subjects will undergo a screening visit to assess eligibility after which a baseline metabolic assessment will be performed including a a fasting oral glucose tolerance test (OGTT) to measure normal glucose and insulin metabolism, an intravenous glucose tolerance test (IVGTT) to measure insulin sensitivity, MRI and DEXA scan to assess muscle and body fat distribution, VO2 max test and resting metabolic rate, and a muscle biopsy to look at how the muscle is affected by insulin and testosterone (T).
Subjects will then be randomized to one of three 12-week treatment arms, 1) Group 1 (Placebo); 2) Group 2 (Depot GnRH agonist (Zoladex) + Testosterone + placebo); or 3) Group 3 (Zoladex + Testosterone + aromatase inhibitor (anastrozole)). The rationale for this study design is as follows. Under normal physiological conditions, administration of T leads to a concomitant increase in estradiol (E2) levels due to endogenous conversion by the aromatase enzyme system. Therefore, in order to understand the relative roles of T and E2 on insulin sensitivity, one group of subjects will receive T in conjunction with the aromatase inhibitor, anastrozole.
At 13 weeks, the entire baseline evaluation including OGTT, IVGTT, resting metabolic rate and VO2 max, body composition assessment by DEXA and MRI, and muscle biopsy will be repeated. Subjects will return for a follow up visit four weeks later to measure CBC, T and PSA levels, to ensure levels are within the normal range.
研究の種類
介入
入学 (予想される)
72
段階
- 適用できない
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
-
-
Maryland
-
Baltimore、Maryland、アメリカ、21224
- Johns Hopkins Bayview Medical Center
-
-
Massachusetts
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Boston、Massachusetts、アメリカ、02114
- Massachusetts General Hospital
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-
参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
50年～75年 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
男
説明
Inclusion Criteria:
- Age 50-75 yr
Diagnosis of the metabolic syndrome defined by the American Heart Association/National Heart, Lung, and Blood Institute guidelines as the presence of three or more of the following:
- Waist circumference > 102 cm
- Serum triglycerides > 150 mg/dL
- HDL cholesterol < 40 mg/dL
- Blood pressure > 130 mm Hg systolic or 85 mm Hg diastolic, or treatment with anti-hypertensives
- Fasting serum glucose > 100 mg/dL
- Plasma total testosterone level less than 300 ng/dL (1 SD below the mean for young healthy men)
- Stable weight for previous three months (no weight change greater than or equal to +/-10 lbs)
- Normal TSH, prolactin and prostate specific antigen (PSA) levels (<2.5 ng/mL)
Exclusion Criteria:
- New diagnosis of type 2 diabetes as defined by the ADA criteria: fasting glucose greater than 126 mg/dL or random blood glucose greater than 200 mg/dL on two occasions, or on oral hypoglycemic agents
- Contraindication to stress testing
- Contraindication to MRI scanning (Central nervous system aneurysm clips; Implanted neural stimulator; Implanted cardiac pacemaker or defibrillator; Cochlear implant; Ocular foreign body (e.g. metal shavings); Insulin pump; Metal shrapnel or bullet)
- History of testicular disorders (i.e. cryptorchidism)
- History of bleeding disorders (i.e. thrombocytopenia) or baseline hemoglobin levels less than 12g/dL
- History of metabolic bone disease (osteoporosis, osteomalacia)
- History of prostate cancer
- History of sleep apnea (subjects will also be excluded if at their baseline assessment they admit to heavy snoring, restless sleep, and/or excessive daytime somnolence)
- Symptoms of urinary outflow obstruction (i.e. benign prostatic hypertrophy)
- Illicit drug use or heavy alcohol use (>4 drinks/day)
- Allergic disorders
Current medications (must exclude individuals taking the following medications):
- Testosterone,
- Cimetidine,
- Spironolactone,
- Ketoconazole,
- Finasteride,
- DHEA,
- Androstenedione,
- Oral steroids,
- GnRH analogs
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：トリプル
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
プラセボコンパレーター：1
1) Group 1: Placebo
|
The IVGTT (70) is a 4 hour study with baseline sampling for insulin and glucose, followed by the administration of 0.3 mg/kg infusion of glucose, and subsequent frequent samples through 180 minutes.
At 20 minutes, subjects will receive a 0.03 U/kg infusion of regular human insulin over 45 seconds to enhance the insulin level to better help us assess the impact of insulin on glucose uptake and to facilitate minimal model analysis.
The IVGTT will be administered at baseline and after 3 months.
他の名前：
This test is employed to assess VO2max in all subjects.
O2 and CO2 will be collected and measured from the expired air during the exercise stress test and used to calculate VO2max.
This test will be administered at baseline and after 3 months.
1H-MR spectroscopy will be performed to measure IMCL at baseline and after 3 months.
Biopsies (20-50mg) will be obtained from the vastus lateralis muscle under local anesthesia (1% lidocaine) using a 5 mm Bergström needle (65) with suction applied.
The muscle biopsy will be performed at baseline and after 3 months.
Energy expenditure in the form of resting metabolic rate (RMR) will be measured via a metabolic monitor at baseline and after 3 months.
Total and regional percent body fat, fat mass, lean tissue mass and bone mineral content will be determined by DEXA (Lunar Prodigy version 8.50).
DEXA provides an in vivo assessment of body composition with minimal requirements for subject cooperation and will be employed at baseline and after 3 months.
他の名前：
To examine glucose and insulin metabolism a standard 75g OGTT will be conducted at baseline and after 3 months.
他の名前：
|
|
アクティブコンパレータ：2
2) Group 2: Depot GnRH agonist (Zoladex) + Testosterone + placebo
|
The IVGTT (70) is a 4 hour study with baseline sampling for insulin and glucose, followed by the administration of 0.3 mg/kg infusion of glucose, and subsequent frequent samples through 180 minutes.
At 20 minutes, subjects will receive a 0.03 U/kg infusion of regular human insulin over 45 seconds to enhance the insulin level to better help us assess the impact of insulin on glucose uptake and to facilitate minimal model analysis.
The IVGTT will be administered at baseline and after 3 months.
他の名前：
This test is employed to assess VO2max in all subjects.
O2 and CO2 will be collected and measured from the expired air during the exercise stress test and used to calculate VO2max.
This test will be administered at baseline and after 3 months.
1H-MR spectroscopy will be performed to measure IMCL at baseline and after 3 months.
Biopsies (20-50mg) will be obtained from the vastus lateralis muscle under local anesthesia (1% lidocaine) using a 5 mm Bergström needle (65) with suction applied.
The muscle biopsy will be performed at baseline and after 3 months.
Energy expenditure in the form of resting metabolic rate (RMR) will be measured via a metabolic monitor at baseline and after 3 months.
Total and regional percent body fat, fat mass, lean tissue mass and bone mineral content will be determined by DEXA (Lunar Prodigy version 8.50).
DEXA provides an in vivo assessment of body composition with minimal requirements for subject cooperation and will be employed at baseline and after 3 months.
他の名前：
To examine glucose and insulin metabolism a standard 75g OGTT will be conducted at baseline and after 3 months.
他の名前：
transdermal 7.5 g/per day for 3 months
他の名前：
single depot injection 10.8 mg 3 months
他の名前：
|
|
アクティブコンパレータ：3
3) Group 3: (Zoladex + Testosterone + aromatase inhibitor (anastrozole)
|
The IVGTT (70) is a 4 hour study with baseline sampling for insulin and glucose, followed by the administration of 0.3 mg/kg infusion of glucose, and subsequent frequent samples through 180 minutes.
At 20 minutes, subjects will receive a 0.03 U/kg infusion of regular human insulin over 45 seconds to enhance the insulin level to better help us assess the impact of insulin on glucose uptake and to facilitate minimal model analysis.
The IVGTT will be administered at baseline and after 3 months.
他の名前：
This test is employed to assess VO2max in all subjects.
O2 and CO2 will be collected and measured from the expired air during the exercise stress test and used to calculate VO2max.
This test will be administered at baseline and after 3 months.
1H-MR spectroscopy will be performed to measure IMCL at baseline and after 3 months.
Biopsies (20-50mg) will be obtained from the vastus lateralis muscle under local anesthesia (1% lidocaine) using a 5 mm Bergström needle (65) with suction applied.
The muscle biopsy will be performed at baseline and after 3 months.
Energy expenditure in the form of resting metabolic rate (RMR) will be measured via a metabolic monitor at baseline and after 3 months.
Total and regional percent body fat, fat mass, lean tissue mass and bone mineral content will be determined by DEXA (Lunar Prodigy version 8.50).
DEXA provides an in vivo assessment of body composition with minimal requirements for subject cooperation and will be employed at baseline and after 3 months.
他の名前：
To examine glucose and insulin metabolism a standard 75g OGTT will be conducted at baseline and after 3 months.
他の名前：
transdermal 7.5 g/per day for 3 months
他の名前：
single depot injection 10.8 mg 3 months
他の名前：
tablet (per oral) 10.0 mg/ daily 3 months
他の名前：
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
時間枠 |
|---|---|
|
insulin sensitivity
時間枠：at baseline and after 3 months
|
at baseline and after 3 months
|
二次結果の測定
結果測定 |
時間枠 |
|---|---|
|
glucose metabolism
時間枠：at baseline and after 3 months
|
at baseline and after 3 months
|
|
body composition VO2 max; resting metabolic rate; muscle biopsy analysis
時間枠：at baseline and after 3 months
|
at baseline and after 3 months
|
|
VO2 max
時間枠：at baseline and after 3 months
|
at baseline and after 3 months
|
|
resting metabolic rate
時間枠：at baseline and after 3 months
|
at baseline and after 3 months
|
|
muscle biopsy analysis
時間枠：at baseline and after 3 months
|
at baseline and after 3 months
|
協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
捜査官
- 主任研究者：Frances J Hayes, MD、Massachusetts General Hospital
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始
2006年5月1日
一次修了 (予想される)
2011年2月1日
研究の完了 (予想される)
2011年3月1日
試験登録日
最初に提出
2007年2月8日
QC基準を満たした最初の提出物
2007年2月8日
最初の投稿 (見積もり)
2007年2月9日
学習記録の更新
投稿された最後の更新 (見積もり)
2010年3月2日
QC基準を満たした最後の更新が送信されました
2010年3月1日
最終確認日
2010年3月1日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- DK71168 (suspended)
- NIDDK # 1 RO1 DK071168-01A2
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。