Hyperinsulinemic Euglycemic Clamp Protocol
A Phase 2A, Double-blind, Placebo-controlled, Randomized Study to Evaluate the Safety and Efficacy of TRC150094 in Increasing Insulin Sensitivity in Male Patients With Increased Cardiometabolic Risk
調査の概要
詳細な説明
20 Subjects will be enrolled in Veeda Clinical research,India and another 20 subjects at Amsterdam, the Netherlands. The maximum duration of participation in the study for each subject will be 9.5 weeks including a less than or equal to 4 weeks screening period, 4 weeks of treatment and a 10 days post treatment follow-up evaluation period.
At each study site, 20 subjects will be enrolled. Each subject will attend the study centre in a fasting state, for a screening visit, 2 study visits (one baseline and one end of treatment), 1 intermediate safety visit and 1 post-study follow-up visit (Total 5 visits). The subjects at each site will be randomized to receive TRC150094 or placebo in a ratio of 1:1. 50 mg dose will be administered once daily (morning) under fasting conditions. Dosing will take place daily on Days 1-28. Subjects will arrive at the study centre for screening visit. Physical examination, vital signs, safety biochemistry and laboratory investigations for verification of inclusion/ exclusion criteria will be performed during screening visit. Subjects meeting all the inclusion criteria and none of the exclusion criteria and who have given their informed consent for the study will be asked to come for the study on Day 0 (or day -1 if required). Baseline investigations (including baseline clamp procedure and hepatic MRS) will be done on Day 0 (or day -1). Subjects will receive properly labelled bottle containing either Active treatment or Placebo as per the randomization number of the subject.
研究の種類
入学 (実際)
段階
- フェーズ2
- フェーズ 1
連絡先と場所
研究場所
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Amsterdam、オランダ、1100 DD
- Academic Medical Centre,
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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:
Subjects will be considered eligible for entry in the study if they meet all of the following criteria.
- Adult male
- Age range 30-65 years at screening
- Caucasian or Indian ethnicity
- Waist circumference ≥ 102 cm for Caucasians and ≥ 90 cm for Indians at screening.
- Fasting Serum Insulin ≥ 10 mU/ml at screening
- Blood Pressure ≥ 130/85 mmHg at screening (or patients taking medication for hypertension)
- Stable weight during 3 months prior to the study (assessed through medical history of the patient)
- Drug naive diabetic patients* or patients with impaired fasting glucose i.e > 100 mg/dl or 5.5 mmol/l and < 200 mg/dl or 11.0 mmol/l Diabetic patients who were taking metformin and have undergone washout for at least 4 weeks before Day 0 and are currently on life style modification as a treatment for diabetes will also be allowed in the study
Willingness to give written informed consent (prior to any study-related procedures being performed) and ability to adhere to the study restrictions and assessments schedule.
- Diabetic patient is defined as a patient with a documented history of type II DM or a documented history of a fasting glucose > 200mg/dl or 11.0 mmol/l or 2x fasting glucose > 126 mg/dl or 6.9 mmol/l (2x =recorded twice).
Exclusion Criteria:
Subjects will not be considered eligible for entry in the study if they meet one or more of the following criteria.
- Medical history, physical examination, vital signs, clinical laboratory tests, 12-lead ECG and Chest X ray (to exclude tuberculosis in India only) with any significant abnormalities, in the opinion of the investigator.
- Subjects with any known somatic illness, including neoplasm, endocrine disorder such as cushing's disease, PCOD and uncontrolled hypothyroidism, neurologic disorder, active infection, or recent surgical procedure within 3 months of the study initiation.
- Subject currently using medication, which can influence glucose or FFA metabolism such as fibrates, niacin, ACE inhibitors, PPAR agonists, omega 3 fatty acids.
- eGFR < 60 mL/min/1.73m2 at screening as evaluated by Modification of Diet in Renal Disease (MDRD) method.
- History of angina, Myocardial Infarction (MI) or stroke since last 6 months.
- Hypertension with SBP/DBP ≥160/100 mmHg at screening.
- ALT or AST ≥ ULN*3 at screening
- History or presence of malignancy.
- History of recreational drug use within the last 30 days, or regular consumption of greater than 2 units of alcohol/day.
- History of allergy to the test drug or any drug chemically similar to the drug under investigation.
- Seropositive for Hepatitis B, Hepatitis C or HIV.
- Subjects suffering from any psychiatric (acute or chronic) illness.
- Intake of any medication except those permitted in this study (see Section 6.6).
- Intake of any investigational drug in the period within 3 months prior to the first dose of study drug.
- History of significant blood loss due to any reason, including blood donation, in the 12 weeks prior to the first dose of study drug; or the total blood loss in the last 3 months, including for this study, exceeds 450 mL.
- History of any bleeding disorder.
- Existence of any surgical or medical condition which, in the judgment of the principal investigator, might interfere with the absorption, distribution, metabolism or excretion of the study drug or might be likely to compromise the safety of the subject.
- Inability to communicate or co-operate with the investigator because of language problems, poor mental development or impaired cerebral function.
- Inability to comply with study requirements.
- Positive drugs of abuse test (at screening) and alcohol breath test.
- Heavy smokers (who are smoking >15 cigarettes or equivalent per day).
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 |
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プラセボコンパレーター:プラセボ
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Tablets once daily
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アクティブコンパレータ:TRC150094
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50 mg Tablets once a day
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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 |
---|---|---|
The safety of TRC150094 once daily dosing for 4 weeks in male patients with increased cardiometabolic risk will be determined.
時間枠:1 month
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Safety parameters will include haematology, safety biochemistry, vital signs, ECG and AE check.
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1 month
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The efficacy (in increasing insulin sensitivity) of TRC150094 once daily dosing for 4 weeks in male patients with increased cardiometabolic risk will be determined.
時間枠:1 month
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Efficacy assessment will include Insulin Sensitivity to be determined by: Rate of Glucose Disposal Suppression of Endogenous Glucose Production Suppression of rate of lipolysis |
1 month
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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 |
---|---|---|
The effect of TRC150094 on hepatic fat and metabolic parameters will be evaluated.
時間枠:1 month
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Early efficacy markers to be explored includes:
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1 month
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The ethnic differences for effect of TRC150094 on Insulin sensitivity parameters will be evaluated.
時間枠:1 month
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Difference in insulin sensitivity parameters (rate of glucose disposal) between caucasian and Indian populations.
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1 month
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協力者と研究者
捜査官
- 主任研究者:Erik Stroes, MD, PhD、Department of Vascular Medicine, AMC
出版物と役立つリンク
一般刊行物
- Zambad SP, Munshi S, Dubey A, Gupta R, Busiello RA, Lanni A, Goglia F, Gupta RC, Chauthaiwale V, Dutt C. TRC150094 attenuates progression of nontraditional cardiovascular risk factors associated with obesity and type 2 diabetes in obese ZSF1 rats. Diabetes Metab Syndr Obes. 2011 Jan 6;4:5-16. doi: 10.2147/DMSOTT.S15323.
- Cioffi F, Zambad SP, Chhipa L, Senese R, Busiello RA, Tuli D, Munshi S, Moreno M, Lombardi A, Gupta RC, Chauthaiwale V, Dutt C, de Lange P, Silvestri E, Lanni A, Goglia F. TRC150094, a novel functional analog of iodothyronines, reduces adiposity by increasing energy expenditure and fatty acid oxidation in rats receiving a high-fat diet. FASEB J. 2010 Sep;24(9):3451-61. doi: 10.1096/fj.10-157115. Epub 2010 May 7.
- van der Valk F, Hassing C, Visser M, Thakkar P, Mohanan A, Pathak K, Dutt C, Chauthaiwale V, Ackermans M, Nederveen A, Serlie M, Nieuwdorp M, Stroes E. The effect of a diiodothyronine mimetic on insulin sensitivity in male cardiometabolic patients: a double-blind randomized controlled trial. PLoS One. 2014 Feb 21;9(2):e86890. doi: 10.1371/journal.pone.0086890. eCollection 2014.
研究記録日
主要日程の研究
研究開始
一次修了 (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
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- CT/P015/CMR/2010/02_01
- 2011-002398-42 (EudraCT番号)
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。
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Placeboの臨床試験
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Palacky University完了
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Advice Pharma Group srl積極的、募集していない肥満 | 栄養障害 | 体重 | 減量 | 食生活 | 太りすぎと肥満 | 健康行動 | ダイエット、健康 | ダイエット習慣 | ライフスタイル | 栄養、健康 | 行動障害イタリア
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Universidade Federal do ParaConselho Nacional de Desenvolvimento Científico e Tecnológico完了
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University Hospital, Strasbourg, France積極的、募集していない