The Effects of Exenatide on Post-Meal Sugar Peaks and Vascular Health in Obese/Pre-Diabetic Young Adults
The Effects of Exenatide on Post-Prandial Glucose Excursions and Vascular Health in Obese/Pre-Diabetic Young Adults
The primary aim of this study is to evaluate the effect of exenatide on daily glycemic excursions obtained by continuous glucose monitoring system (CGMS). The CGMS summary parameters that we are most interested in include:
- The percent of glucose values above 140 mg/dl and/or AUC of glucose values above 140 mg/dl
- AUC of glucose values over 100 mg/dl during three days
- Maximal meal-related glucose excursions
- Three-day mean glucose (including low readings - below 100 mg/dl)
Secondary Study Endpoints:
Secondary endpoints will include:
- glucose tolerance status as assessed by OGTT
- Vascular function scores as assessed by PAT, FMD and step test.
- Biochemical markers of vascular health, including inflammatory markers, markers of oxidative stress and microalbuminuria.
- Changes in BMI
調査の概要
詳細な説明
Obese insulin resistant adolescents with impaired glucose tolerance (IGT) or evidence of glucose excursions ≥ 140 mg/dl on CGMS will be enrolled in a two armed randomized, parallel group - open label study. There will also be a lean control group for baseline assessments only.
One arm will be exenatide the other arm will be no drug. Subjects will be stratified according to state of glucose tolerance. Stratification will also occur according to gender and family history of premature cardiovascular disease.
Obese adolescents age 16-25 years with a family history of type 2 diabetes, whom have completed or reached tanner IV stage of pubertal development and have normal or impaired oral glucose tolerance. Obese adolescents age 13-15 with a family history of type 2 diabetes, whom have completed or reached tanner III stage of pubertal development and have impaired oral glucose tolerance with a 2-hour glucose of 180-199 mg/dl will also be invited to participate. For cardiovascular assessment only age matched lean control subjects without diabetes will be recruited.
Obese subjects will have a baseline and post intervention oral glucose tolerance test (OGTT), screening labs (liver/kidney functions, lipid profile, thyroid function tests, CBC, metabolic and cardiovascular laboratory parameters -- such as inflammatory cytokines and pro-thrombotic factors), wear a CGMS for 3-days on 3 separate occasions (baseline, 2-month and 4-month), have a standardized snack once during each CGMS session, collect urine samples for microalbumin and have vascular tests (PAT, FMD and exercise step test) done at baseline and post intervention.
Subjects randomized to treatment will undergo a four month intervention with exenatide on the following dosing schedule: exenatide - 5 μg twice a day for 7 days, followed by exenatide 10 μg twice a day for the remainder of the four month intervention.
Lean Control Subjects:
As for obese subjects, lean subjects will be asked to bring in first morning voids for testing of microalbuminuria. They will also have endothelial function tests (PAT, FMD and step test) as well as CGMS placement. A set of screening labs will also be drawn (fasting glucose, insulin, thyroid function and lipid profile will be drawn). Furthermore blood will be collected for analysis of novel cardiovascular parameters (such as inflammatory cytokines and pro-thrombotic factors). However lean subjects will not have an OGTT done and will not be offered drug intervention. The endothelial function testing in the lean controls will serve as control data for the vascular function testing in the obese children. The CGMS data of the lean controls will allow us to better interpret changes in the post-meal excursions seen in obese children after exenatide intervention. Similar to obese subjects, lean subjects will be instructed to take a standardized snack in the afternoon prior to returning for CGMS removal. The snack will be provided for them to take home at the end of their CGMS placement visit and will include two pop-tarts and an orange soda. Lean control subjects will wear the CGMS for three days. At the end of the monitoring period the subject will return for their CGMS removal visit.
研究の種類
段階
- フェーズ 4
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
Obese subjects:
Major Inclusion Criteria:
- Obesity (BMI > 97%tile for age and sex matched normative data)
- Insulin resistance: fasting insulin> 25 mIU/ml
- Good general health, taking no medication on a chronic basis
- Age 16-25 yrs, late pubertal stage (girls: breast: Tanner stage IV to V, boys: testicular volume > 15 ml) or age 13-15 yrs (with a family history of type 2 diabetes, whom have completed or reached tanner stage III and have impaired oral glucose tolerance with a 2-hour glucose of 180-199 mg/dl)
- Girls who are sexually active must use adequate birth control methods (such as barrier method or oral contraception) and must have a negative pregnancy test
- Normal liver function tests
Major Exclusion Criteria:
- Hx of gallstones
- Elevated triglycerides >400 mg/dl
- Hx of alcohol use/ binge drinking
- Raynaud's syndrome
- Pregnancy or breastfeeding mothers
- Cigarette smokers
- Anemia (Hct < 35)
- Baseline creatinine > 1.0 mg
- Abnormal liver transaminases > 2.0 X the upper limit of normal
- Presence of endocrinopathies except for adequately treated hypothyroidism
- Presence or history of gastrointestinal disorders (inflammatory bowl disease, irritable bowl disease, hernia, ileus)
- Presence of significant chronic illness of any kind.
- Use of any drugs that might be expected to affect glucose tolerance, insulin resistance or weight gain, cardiovascular health.
- Psychiatric disorders
- History of substance abuse
Lean Control Subjects (only for cardiovascular studies and CGMS):
Inclusion Criteria:
- Lean (BMI < 85%tile for age and sex matched normative data)
- Fasting insulin <15 mIU/m
- Fasting glucose <100 mg/dll
- Excellent general health, having no acute or chronic health problems and taking no current medications
- Age 13-25 yrs, in puberty (age matched with obese subjects)
- Girls who are sexually active must use adequate birth control methods (such as barrier method or oral contraception) and must have a negative pregnancy test
Exclusion Criteria:
- Raynaud's syndrome
- Pregnancy or breastfeeding mothers
- Cigarette smokers
- Psychiatric disorders
- History of substance abuse
- First degree relative with either T1DM or T2DM
- Presence of acanthosis nigricans
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：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 |
|---|---|
|
介入なし：治療なし
|
|
|
実験的：Exenatide
Subjects randomized to treatment will receive a four month supply of exenatide.
|
Subjects randomized to treatment will receive a four month supply of exenatide and will be taught how to administer subcutaneous injections with their exenatide pen and instructed on the following dosing schedule: exenatide - 5 μg twice a day for 7 days, followed by exenatide 10 μg twice a day for the remainder of the four month supply.
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 |
|---|---|
|
Whether treatment with exenatide attenuates post-prandial glycemic excursions as assessed by oral glucose tolerance testing (OGTT) and continuous monitoring system (CGMS) technology.
時間枠：OGTT (Pre- and post-intervention), CGMS (Pre-intervention, 2-months and post-intervention)
|
OGTT (Pre- and post-intervention), CGMS (Pre-intervention, 2-months and post-intervention)
|
二次結果の測定
結果測定 |
時間枠 |
|---|---|
|
Cardiovascular risk parameters will be assessed via flow mediated vasodilation, peripheral arterial tonometry, a self-paced step test and biochemical markers of vascular health.
時間枠：Pre- (baseline) and post- (4-months) intervention
|
Pre- (baseline) and post- (4-months) intervention
|
|
Change in body mass index (BMI).
時間枠：Pre-intervention, 2-month and post-intervention.
|
Pre-intervention, 2-month and post-intervention.
|
協力者と研究者
スポンサー
捜査官
- 主任研究者：Tania S Burgert, MD、Yale School of Medicine
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)
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。