Adding Liraglutide to High Dose Insulin: Breaking the Cycle
2017年12月15日 更新者：Ildiko Lingvay
The purpose of this study is to evaluate whether the addition of liraglutide 1.8 mg/day to a high-dose insulin regimen (>1.8 units/kg/day) in patients with uncontrolled (HbA1c >7.5%) type 2 diabetes mellitus will improve blood sugar control.
It also evaluates the effect of liraglutide on liver and pancreatic fat content, explores the mechanism of blood sugar improvement by assessing weight and pancreatic hormone release, and assesses blood pressure, lipid profile, and liver function. Finally it will look at patient quality of life and safety.
調査の概要
詳細な説明
Type 2 diabetes is a progressive disease with incessant beta-cell dysfunction that often ultimately requires insulin treatment. Patients requiring high insulin dosages represent a particular treatment challenge and often have uncontrolled glycemia despite progressive dose increases and are especially prone to insulin related lipotoxicity and weight gain.
Glucagon-like peptide agonists (GLP-1) such as liraglutide have many actions that position them to break the vicious cycle in this population through the following mechanisms: (1) weight loss; (2) improved hepatic steatosis; (3) improved pancreatic steatosis; (4) decreased glucagon levels; (5) improved beta-cell function.
The purpose of the study is to demonstrate that liraglutide is both effective and safe when added to a high dose insulin treatment regimen. Liraglutide will improve glycemic control, weight, metabolic parameters, as well as patient satisfaction, with minimal adverse events. The study also proposes to study the mechanisms through which such improvements might occur, especially beta-cell function, glucagon levels, and hepatic and pancreatic fat content.
研究の種類
介入
入学 (実際)
71
段階
- フェーズ 4
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
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Texas
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Dallas、Texas、アメリカ、75390
- UT Southwestern
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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
18年歳以上 (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
全て
説明
Inclusion Criteria:
- Type 2 diabetes mellitus
- Insulin dose of >1.8 units/kg/day (represents total daily insulin dose, regardless of formulation, regimen, number of daily shots)
- HbA1c ≥ 7.5% and ≤ 11%
- Age ≥ 18
- Stable comorbidities on stable treatment regimens
- Stable dose of all oral hypoglycemics for ≥ 3 months prior to enrollment
- Ability to provide informed consent before any trial-related activities
Exclusion Criteria:
- Type 1 diabetes mellitus
- Any contraindication to the MRI procedure (metallic implants, severe claustrophobia, pregnancy, unable to lie still on a hard table for the duration of the procedure, weight above 400 lb - limit of the MRI table, magnet's inner circumference smaller than the largest body circumference)
- History of any pancreatic disease as it might interfere with the pancreatic TG measurement (i.e. pancreatitis, tumors, cysts, type 1 diabetes, any pancreatic surgery)
- End Stage Renal Disease on dialysis due to increased risk of hypoglycemia, and possible interference with accurate measurement of HbA1c
- Incretin therapy (any GLP-1 agonist or DPP-IV inhibitor)
- Unstable or decompensated comorbidities
- Personal or family history of medullary thyroid carcinoma or MEN-2 syndrome
- Severe gastroparesis
- Pregnancy, breast feeding, intention to become pregnant, or not using adequate contraceptive measures
- Organ transplant recipient or waiting list candidate
- Steroid use (current or potential use during the trial)
- Known/suspected allergy to trial medication, excipients, or related products
- Contraindications to study medications, worded specifically as stated in the product's prescribing information
- Non-English speaking volunteers since no interpreters are available and the safety of the volunteers could be jeopardized if adequate and reliable communication is not possible.
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 |
|---|---|
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アクティブコンパレータ：リラグルチド
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Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months
他の名前：
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プラセボコンパレーター：生理食塩水注射
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Placebo injection of 1.8mg saline once daily for 6-months
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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 |
|---|---|---|
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Glycemic Control Measured by HbA1c
時間枠：6-months
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HbA1c (%)
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6-months
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Pancreatic and Hepatic Triglyceride Content
時間枠：6-months
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Liver Triglyceride and Pancreatic Triglyceride
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6-months
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Weight
時間枠：6-months
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6-months
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Beta-Cell Function
時間枠：6-months
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Fasting Glucose as a Measure of Beta-Cell Function
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6-months
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Glucagon
時間枠：6-months
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Measured during mixed meal challenge test.
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6-months
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Total Daily Insulin Dose
時間枠：6-months
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The 3 days average of the total daily dose of insulin used within 3 consecutive days prior office visit 6 month.
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6-months
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Number of Daily Injections
時間枠：6-months
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The 3 days average of the number of daily injections performed within 3 consecutive days prior office visit 6 month.
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6-months
|
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Blood Pressure
時間枠：6-months
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6-months
|
|
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Lipid Profile
時間枠：6-months
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6-months
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|
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Liver Function Blood Test
時間枠：6-months
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6-months
|
|
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Hypoglycemic Events
時間枠：6-months
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Reported as hypoglycemic events per month by patient as any blood glucose <70 mg/dl or symptoms of hypoglycemia with blood glucose >70 mg/dl
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6-months
|
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Quality of Life Survey (QoL) - General Health Perception
時間枠：6-months
|
General health perception was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a Likert scale score of 1-5, where 1 = excellent; 2 = very good; 3 = good; 4 = fair; 5 = poor.
|
6-months
|
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Beta-Cell Function
時間枠：6 months
|
Fasting C-peptide as a Measure of Beta-Cell Function
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6 months
|
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Matsuda Index as a Measure of Beta Cell Function
時間枠：6 months
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The Matsuda index is a measure of insulin sensitivity and has no minimum/maximum values.
Index values are calculated as 500,000/square root of ((fasting glucose x fasting c-peptide x 333) x (mean 120 min post-meal glucose x mean 120 min post-meal c-peptide x 333)).
Higher/lower values = better/worse insulin sensitivity.
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6 months
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Beta-cell Function
時間枠：6 Months
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AUC c-peptide
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6 Months
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Ratio (AUC C-peptide/AUC Glucose)
時間枠：6 months
|
6 months
|
|
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AUC Glucose
時間枠：6 months
|
6 months
|
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Quality of Life Survey (QoL) - Current Health Perception
時間枠：6 months
|
Current health perception was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a Likert scale score of 1-5, where 1 = much better than 3 months ago; 2 - Somewhat better now than 3 months ago; 3 - About the same; 4 - Somewhat worse now than 3 months ago; 5 Much worse now than 3 months ago.
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6 months
|
|
Quality of Life Survey (QoL) - Treatment Satisfaction
時間枠：6 months
|
Quality of Life Survey (QoL) - treatment satisfactionTreatment satisfaction was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a Likert scale score of 1-5, where 1 - very satisfied; 2 - moderately satisfied; 3 - neither satisfied nor dissatisfied; 4 - moderately dissatisfied; 5 - very dissatisfied.
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6 months
|
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Quality of Life Survey (QoL) - Treatment Impact
時間枠：6 months
|
Treatment impact was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a Likert scale score of 1-5, where 1 - very satisfied; 2 - moderately satisfied; 3 - neither satisfied nor dissatisfied; 4 - moderately dissatisfied; 5 - very dissatisfied.
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6 months
|
|
Quality of Life Survey (QoL) - Social or Vocational Worry
時間枠：6 months
|
Social or vocational worry was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a Likert scale score of 0-5, where 0 - does not apply; 1 - never; 2 - seldom; 3 - sometimes; 4 - often; 5 - all of the time.
|
6 months
|
|
Quality of Life Survey (QoL) - Hypoglycemia Fear
時間枠：6 months
|
Hypoglycemia fear was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a Likert scale score of 1-5, where 1 - never worry; 2 - rarely water; 3 - sometimes worry; 4 - often worry; 5 - very often worry.
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6 months
|
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Quality of Life Survey (QoL) - Glycemia Control Perception
時間枠：6 months
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Glycemia control perception was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a scale score of 1-7, where 1 - extremely controlled and 7 - not at all controlled.
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6 months
|
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Quality of Life Survey (QoL) - Lifestyle Flexibility
時間枠：6 months
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Lifestyle flexibility was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a Likert scale score of 1 to 5, where 1 - a great deal of choice; 2 - a lot of choice; 3 - some choice; 4 - a little choice; 5 - no choice.
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6 months
|
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Quality of Life Survey (QoL) - Social Stigma
時間枠：6 months
|
Social stigma was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a Likert scale score of 1 to 5, where 1 strongly agree; 2 - somewhat agree; 3 - neither agree nor disagree; 4 - somewhat disagree; 5 - strongly disagree.
|
6 months
|
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Quality of Life Survey (QoL) - Satisfaction With Insulin Treatment
時間枠：6 months
|
Satisfaction with insulin treatment was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a scale score of 1 to 7, where 1 extremely satisfied to 7 - not at all satisfied.
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6 months
|
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Quality of Life Survey (QoL) - Willingness to Continue Insulin Treatment
時間枠：6 months
|
Willingness to continue insulin treatment was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a scale score of 1 to 7, where 1 extremely willing to 7 - not at all willing.
|
6 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。
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。
一般刊行物
- Vanderheiden A, Harrison L, Warshauer J, Li X, Adams-Huet B, Lingvay I. Effect of Adding Liraglutide vs Placebo to a High-Dose lnsulin Regimen in Patients With Type 2 Diabetes: A Randomized Clinical Trial. JAMA Intern Med. 2016 Jul 1;176(7):939-47. doi: 10.1001/jamainternmed.2016.1540.
- Vanderheiden A, Harrison LB, Warshauer JT, Adams-Huet B, Li X, Yuan Q, Hulsey K, Dimitrov I, Yokoo T, Jaster AW, Pinho DF, Pedrosa I, Lenkinski RE, Pop LM, Lingvay I. Mechanisms of Action of Liraglutide in Patients With Type 2 Diabetes Treated With High-Dose Insulin. J Clin Endocrinol Metab. 2016 Apr;101(4):1798-806. doi: 10.1210/jc.2015-3906. Epub 2016 Feb 24.
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
2012年1月1日
一次修了 (実際)
2016年6月1日
研究の完了 (実際)
2016年6月1日
試験登録日
最初に提出
2012年1月4日
QC基準を満たした最初の提出物
2012年1月5日
最初の投稿 (見積もり)
2012年1月6日
学習記録の更新
投稿された最後の更新 (実際)
2018年1月16日
QC基準を満たした最後の更新が送信されました
2017年12月15日
最終確認日
2017年12月1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。