Evaluation of the DPP-4 Inhibitor Sitagliptin in the Treatment of Non-Alcoholic Fatty Liver Disease Using MRI
Pilot Project Evaluation of the DPP-4 Inhibitor Sitagliptin in the Treatment of Non-Alcoholic Fatty Liver Disease Using MRI
Participants will be persons with type 2 diabetes who are likely to have fatty liver disease. The investigators think that this medication will reduce fatty liver.
The investigators will use an MRS (a non invasive method using magnets) to evaluate liver fat before and after subjects take a diabetes medication. The investigators will also collect a small amount of blood to measure liver, kidney and hormone functions. This will be done 4 times. Also, at the time of the subject gets their first dose of medication they will have a DEXA (low exposure x-ray often used in clinical practice to measure bone density and body composition).
The goal of all of these studies is to determine whether the study drug lowers liver fat.
調査の概要
詳細な説明
Non-alcoholic fatty liver disease (NAFLD) and its progression to non-alcoholic steatohepatitis (NASH) and finally cirrhosis is rapidly becoming the leading cause of liver injury and end stage liver disease, particularly in industrialized countries. Though several pharmacologic agents (i.e. metformin, pioglitazone and others) have been suggested to have benefit in reducing the progression of this disease, none is approved for use.
The causes of NAFLD and NASH are unknown, though visceral obesity, metabolic syndrome and type 2 diabetes are recognized co-existent risk factors. Recent evidence has linked NAFLD to elevated dipeptidyl peptidase-4 (DPP-4). DPP-4 levels in the plasma and livers of persons with NAFLD are elevated and correlate with elevations in liver enzymes, though not with markers of insulin resistance alone.
It has been proposed that increased DPP-4 activity in combination with decreased PPAR signaling stimulates the inflammatory response that leads to liver fibrosis in the transition of NASH to cirrhosis. Debate exists as to whether the effect of DPP-4 in the liver is via its effect on the intestinal hormones or its direct effects on liver tissue. Indeed some studies have found reductions in liver fat with administration of GLP-1 agonists in animal models of obesity.
研究の種類
段階
- フェーズ 4
連絡先と場所
研究場所
-
-
Missouri
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Columbia、Missouri、アメリカ、65212
- University of Missouri-Columbia: Diabetes Center
-
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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:
- Type 2 diabetes mellitus with hemoglobin A1c above 6.5%.
- Waist circumference over 40 inches in a male or 35 inches in a female or BMI greater than 30.
- Age between 18 and 70 years.
- Stable on maximum tolerated dose of metformin for at least 3 months prior to enrollment.
- Sedentary (less than 30 minutes per week of structured activity) and weight stable (2% body weight in past 6 months).
- Metabolic syndrome based on NCEP ATP-3 guidelines with diabetes accepted as the glycemic component.
- For women: at least 2 years postmenopausal, surgically sterile, or using an acceptable contraceptive regimen to include OCP, IUD, double barrier, depo-provera, or subcutaneous progestin implant and negative urine pregnancy test at trial start.
- For men: surgically sterile or agreement that any female partner meet criteria of 7.
Exclusion Criteria:
- Pregnancy, breast feeding, or planning to become pregnant during the study period.
- GFR less than 60mL per minute per meter squared.
- Any medical condition expected to be terminal within one year.
- Cirrhosis of any cause or liver disease due to auto-immune, infectious or alcohol induced hepatitis.
- Active mental illness or other condition which in the opinion of the investigator would prevent informed consent or compliance with study protocol.
- Use of PPAR agonist within six months prior to enrollment.
- Daily insulin use.
- Allergy or intolerance of sitagliptin or other DPP-4 inhibitor.
- Use of DPP-4 inhibitor, bile acid sequesterant, or weight loss medications within three months prior to enrollment.
- Significant alcohol use defined as greater than 21 standard servings of alcohol (10gms) per week for men and greater than 14 for women.
- History of bariatric surgery or planned bariatric surgery during the study period.
- Weight, girth, or other factor preventing MRI scanning.
- Receipt of another study drug within 30 days of screening.
- Unable to receive a DEXA scan due to participating in research study or medical procedure involving ionizing radiation exposure equivalent to a chest x-ray or greater in the past 12 months.
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：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：Sitagliptin
60 day supply of 100mg Sitagliptin
|
60 day supply of 100mg Sitagliptin.
The investigators will use an MRS (a non invasive method using magnets) to evaluate liver fat before and after subjects take a diabetes medication.
The investigators will also collect a small amount of blood to measure liver, kidney and hormone functions.
This will be done 4 times.
Also, at the time of the subject gets their first dose of medication they will have a DEXA (low exposure x-ray often used in clinical practice to measure bone density and body composition).
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 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Change in Liver steatosis
時間枠：baseline and Six months
|
Steatosis measured by Magnetic Resonance Spectroscopy
|
baseline and Six months
|
協力者と研究者
研究記録日
主要日程の研究
研究開始
一次修了 (予想される)
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
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
- MERCK-9938
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
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