Effect of Insulin Sensitizer Therapy on Atherothrombotic and Inflammatory Profiles Associated With Insulin Resistance
調査の概要
詳細な説明
Individuals with diabetes mellitus (DM) are disproportionately affected by atherothrombotic disorders, including cardiovascular, cerebrovascular, and peripheral vascular diseases. Atherothrombotic disease risk and mortality are also increased with metabolic syndrome, a constellation of risk factors present in more than 34% of adults, even in absence of diabetes. Yet, large clinical trials of diabetes therapies have shown that conventional cardiovascular disease (CVD) risk factors, specifically hyperglycemia and hypertension, do not fully account for increased CVD risk associated with DM.
There may be an etiologic link among insulin resistance, inflammation and thrombotic events. This study seeks to determine if certain two diabetes medications (the insulin sensitizing medications) will affect certain biomarkers (or laboratory tests) for CVD in individuals with untreated DM or impaired fasting glucose.
Patients will be screened for inclusion into this this double-blinded, randomized), placebo-controlled study. If inclusion criteria are met and exclusion criteria not met, patients will be enrolled in the the study. Half of the subjects will be randomized (like the flip of a coin) to take two insulin sensitizing, anti-diabetic drugs pioglitazone (Actos) and metformin (Glucophage) taken together for three months and the other half of the subjects will take corresponding placebo (dummy) tablets.
Laboratory measurements will be obtained on the morning(s) following the two in-patient overnight stays in the Mayo Clinic Clinical Research Unit. The first stay will be at baseline and the second stay will be 3 months after baseline. Insulin sensitivity will be measured in the morning following a standardized meal the preceding night, and after an overnight fast.
The changes (from baseline to 3 months) in insulin sensitivity, glycemic control, the lipid profile, thrombotic markers and inflammatory markers will be determined and compared between the two arms of the study (placebo versus insulin sensitizing drugs).
研究の種類
入学 (実際)
段階
- フェーズ2
連絡先と場所
研究場所
-
-
Minnesota
-
Rochester、Minnesota、アメリカ、55905
- Mayo Clinic
-
-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion criteria:
- We will study 30 patients with Type 2 Diabetes or impaired fasting glucose (15 men & 15 women) who are > 20 years old.
- Only patients who use lifestyle modification to manage their diabetes and are not on any oral hypoglycemic agents or insulin will be included.
- We will enroll subjects who have fasting glucose concentration greater than 100 mg/dl on two consecutive occasions and have a Body Mass Index between 27-36 kg/m^2.
Exclusion Criteria:
- We will exclude patients whose blood glucose is above 180 mg/dl. This will avoid the need to perform home glucose monitoring and the potential of unblinding the study by the volunteers.
- Patients taking oral hypoglycemic agents or insulin would be excluded.
- Any diseases such as active cardiovascular disease, liver diseases, kidney failure (males with serum creatinine >= 1.5mg/dl, females >=1.4 mg/dl), active endocrinopathies, debilitating chronic disease, anemia, symptoms of undiagnosed illness, history of alcoholism (alcohol use > 4oz/day) or substance abuse, chronic neurological diseases including Alzheimer's disease, stroke, etc, myopathies or any other active disease that may potentially affect the outcome measures.
- Patients on medicines such as beta blockers, corticosteroids, tricyclics, benzodiazepines, opiates, barbiturates, anticoagulants and any other drugs or preparations that may affect mitochondrial function will be excluded.
- People allergic to any of the class of drug such as lidocaine will also be excluded.
- People with pacemakers, certain aneurysm clips and claustrophobia will also be excluded as they cannot undergo magnetic resonance imaging.
研究計画
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：ダブル
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
アクティブコンパレータ：Insulin Sensitizer Therapy
Two insulin sensitizing drugs will be taken together for 3 months; metformin 1000 mg twice daily plus pioglitazone 45 mg daily.
|
To minimize side effects the metformin will be initiated at 500 mg twice daily with meals and increased to 1 gm twice daily with meals after two weeks and continue to a total of 3 months of dosing.
他の名前：
To minimize side effects, the pioglitazone will be initiated at 30 mg daily and increased to 45 mg daily after two weeks, and continue to a total of 3 months of dosing.
他の名前：
|
|
プラセボコンパレーター：Placebo
Placebo tablets were used to match the active comparator drugs and dosing regimen.
|
Placebo tablets matching the metformin and pioglitazone tablets are given in the same regimen as the active drug arm for 3 months.
|
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 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Change From Baseline in Insulin Sensitivity as Measured by Glucose Infusion Rate (GIR)
時間枠：Baseline, 3 months
|
Insulin sensitivity was measured the morning after an overnight fast during an in-patient stay in the Clinical Research Unit & was determined by the mean GIR necessary to maintain euglycemia during a hyperinsulinemic (1.5 mcIU/kg of FFM per minute)-euglycemic (85-95 mg/dL) clamp.
The clamp is an 8 hour process where a hand vein is catheterized to collect blood samples and intravenous lines are used to infuse glucose, saline, insulin, phenylalanine and amino acid solutions at at pre-specified times/rates.
The mean GIR was calculated as the rate per kilograms of fat-free mass (FFM) during 4 hours of steady-state (hours 4-8 of the 8 hour clamp) reported as micromols/kilogram of FFM per minute.
The FFM was measured by dual-energy x-ray absorptiometry (DEXA) scan.
Insulin was infused with 5% essential amino acid solution (3mL/kg of FFM/hour) to prevent the insulin-dependent decrease of amino acids during insulin infusion.
|
Baseline, 3 months
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Change From Baseline in Fasting Blood Glucose Level
時間枠：Baseline, 3 months
|
Glucose (sugar) was measured in the blood and reported in milligrams per deciliter (mg/dL).
|
Baseline, 3 months
|
|
Change From Baseline in Glycosylated Hemoglobin (HbA1c)
時間枠：Baseline, 3 months
|
HbA1c is a measure of average blood sugar levels over the preceding 3 month period.
HbA1c was measured by ion-exchange chromatography and reported as a percentage.
|
Baseline, 3 months
|
|
Change From Baseline in Insulin Levels
時間枠：Baseline, 3 months
|
Insulin levels in the blood were measured by immunoenzymatic assay and reported in micro International Units per milliliter (mcIU/mL).
|
Baseline, 3 months
|
|
Change From Baseline in Lipid Profile
時間枠：Baseline, 3 months
|
Change in lipids were measured by the change from baseline to 3 months of triglycerides, high-density lipoprotein cholesterol (HDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C).
All were reported in milligrams/deciliter (mg/dL).
|
Baseline, 3 months
|
|
Change From Baseline in the Thrombotic Biomarker Fibrinogen
時間枠：Baseline, 3 months
|
Fibrinogen was measured by thrombin clotting rate assay (Beckman Coulter, Inc. Brea, California) and reported in milligrams/deciliter (mg/dL).
|
Baseline, 3 months
|
|
Change From Baseline in the Thrombotic Biomarker Plasminogen Activator Inhibitor-1 (PAI-1)
時間枠：Baseline, 3 months
|
PAI-1 was measured by enzyme-linked immunosorbent assay (Diagnostica Stago Inc., Parsippany, New Jersey) and reported in nanograms per milliliter (ng/mL).
|
Baseline, 3 months
|
|
Change From Baseline in the Inflammatory Biomarker Interleukin 6 (IL-6)
時間枠：Baseline, 3 months
|
IL-6 is an inflammatory cytokine and reported in picograms per deciliter (pg/dL).
|
Baseline, 3 months
|
|
Change From Baseline in the Inflammatory Biomarker C-Reactive Protein (CRP)
時間枠：Baseline, 3 months
|
CRP is an inflammatory cytokine and is reported in milligrams per deciliter (mg/dL).
|
Baseline, 3 months
|
|
Change From Baseline in Inflammatory Biomarker Tumor Necrosis Factor-alpha (TNF-α)
時間枠：Baseline, 3 month
|
TNF-α is an inflammatory cytokine and is reported in picograms/milliliter (pg/mL).
|
Baseline, 3 month
|
|
Change From Baseline in the Inflammatory Biomarker Adiponectin
時間枠：Baseline, 3 months
|
Adiponectin is an anti-inflammatory cytokine and is reported in milligrams per milliliter (mg/mL).
|
Baseline, 3 months
|
その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Change From Baseline in Body Mass Index
時間枠：Baseline, 3 months
|
Body Mass Index (BMI) is a health index for comparing weight to height.
BMI is a person's weight in kilograms (kg) divided by his or her height in meters squared.
The body mass index is an indication if a person is at a suitable weight for his height on an approximation of body fat.
|
Baseline, 3 months
|
|
Change From Baseline in Body Fat
時間枠：Baseline, 3 months
|
Body fat is reported as a percentage of body weight.
|
Baseline, 3 months
|
|
Change From Baseline in Fat-Free Mass (FFM)
時間枠：Baseline, 3 months
|
FFM was measured using dual energy x-ray absorptiometry (DEXA) scans and is reported in kilograms (kg).
|
Baseline, 3 months
|
協力者と研究者
出版物と役立つリンク
一般刊行物
- McCoy RG, Irving BA, Soop M, Srinivasan M, Tatpati L, Chow L, Weymiller AJ, Carter RE, Nair KS. Effect of insulin sensitizer therapy on atherothrombotic and inflammatory profiles associated with insulin resistance. Mayo Clin Proc. 2012 Jun;87(6):561-70. doi: 10.1016/j.mayocp.2012.02.014. Erratum In: Mayo Clin Proc. 2013 Aug;88(8):903-4.
- Irving BA, Carter RE, Soop M, Weymiller A, Syed H, Karakelides H, Bhagra S, Short KR, Tatpati L, Barazzoni R, Nair KS. Effect of insulin sensitizer therapy on amino acids and their metabolites. Metabolism. 2015 Jun;64(6):720-8. doi: 10.1016/j.metabol.2015.01.008. Epub 2015 Jan 22.
便利なリンク
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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。