- ICH GCP
- Registro de ensaios clínicos dos EUA
- Ensaio Clínico NCT01859793
Effects of Sitagliptin on Endothelial Function in Type 2 Diabetes on Background Metformin Therapy
A Randomized, Crossover Design Study of Acute and Chronic Effects of Sitagliptin on Endothelial Function in Humans With Type 2 Diabetes on Background Metformin
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
We plan to recruit 38 patients with T2DM for this single center, double blind randomized, interventional crossover trial comparing sitagliptin (100 mg/day) to matching placebo. We have chosen placebo over a comparator for this study as our goal is to determine whether sitagliptin both improves glycemic control and endothelial function, properties not shared by other popular classes of agents like sulfonylureas. Subjects will be randomized with a 1:1 allocation ratio to either sitagliptin 1st or placebo 1st.
The study have 5 total visits. Subjects who pass a phone screen will be invited to a screening visit for study eligibility (Visit 1) Informed consent will be reviewed; a unique study number will be assigned once written informed consent is obtained (no subject will be assigned more than 1 allocation number); relevant participant medical history will be recorded including currently prescribed medications; anthropometric measurements will be taken (height, weight, and waist circumference in metric units) and blood pressure will be recorded (measured in triplicate and averaged). Subjects will be allowed to take their blood pressure medication on the morning of their screening visit, but not the mornings of any of the other study visits to limit the acute influence of these medications on endothelial function. If the potential participant qualifies for the study, he/she will be randomized either to receive sitagliptin 1st (100 mg/day) or matching placebo. Prior to receiving either of set of pills, subjects will return to the study center within approximately 1-2 weeks of the screening visit to undergo initial tests of endothelial function and receive their pills. Prior to all study visits except screening, subjects will also be asked to refrain from any vigorous physical activity (no weight lifting, jogging or any activity vigorous than walking) 24 hours to reduce the risk of fasting hypoglycemia during the study visits. Subjects will also be asked to fast for 6-8 hours prior to the visit to limit the acute dietary influences on vascular endothelial function. At Visit 2, endothelial function will determined by brachial artery reactivity testing prior to and following a single dose of 100 mg of sitagliptin or matching placebo depending on the arm to which the subject was randomized. Blood samples will also be taken at this visit for systemic measurements of endothelial cell activation/inflammation (VCAM-1 and ICAM-1) prior to and 2 hours following acute drug administration. These will be measured at the indicated time points using commercially available kits.
Endothelial function, like the blood samples, will be measured just prior to medication administration and then 2 hours following medication administration by brachial artery reactivity testing as described in Section D.3. The 2 hour time from was chose in given the plasma levels of sitagliptin appear to peak 2 hours following dose administration.32 At the end of this visit, subjects will be given a 9 week supply of the study pills (sitagliptin or matching placebo) as dispensed by the Froedtert Hospital Investigational Pharmacy, and scheduled to return for Visit 3 approximately 8 weeks following Visit 2. Subjects will be asked to not take any study medication for the 24 hours prior to Visit 3. At Visit 3, subjects will undergo repeat testing of endothelial function. Following this study visit, subjects will remain off study pills until they return for Visit 4 approximately 4 weeks following Visit 3. Visit 4 repeats Visit 2 except subjects will receive the set of pills to which they had been randomized to receive second. Subjects will return to the study center for Visit 5 approximately 8 weeks after Visit 4. Visit 5 is identical to Visit 3. Subject adherence will be determined by pill counts performed by MCW Translational Research Unit nursing staff who will perform all pill accounting. All medication dispensation will be handled by the Froedtert Hospital Investigational Drug Pharmacy.
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 4
Contactos e Locais
Locais de estudo
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Wisconsin
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Milwaukee, Wisconsin, Estados Unidos, 53226
- Medical College of Wisconsin
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
- Adult age 21-70 years of age.
- Diagnosis of type 2 diabetes by a physician as defined by the American Diabetes Association standard criteria: 1) Fasting Plasma glucose at or above 126 mg/dL 2) a two-hour value in an oral glucose tolerance test at or above 200 mg/dL, or 3) a random plasma glucose concentration 200 mg/dL in the presence of symptoms, or 4) glycosylated hemoglobin greater than or equal to 6.5%.
- On stable metformin therapy for at least 6 weeks prior to enrollment.
- Glycosylated Hemoglobin ≥6.2% and ≤ 9.5%.
Exclusion Criteria:
- History of stroke, peripheral arterial disease, or coronary artery disease (as defined by the presence of at least one coronary stenosis ≥ 50% on angiography or by confirmed history of myocardial infarction by standard criteria.)
- Evidence of other evident major illness including chronic renal insufficiency (creatinine clearance less than 60 mL/min),chronic liver disease (AST or ALT greater than 2.5 x normal), or cancer currently undergoing systemic therapy or had systemic therapy for cancer within 1 year of enrollment.
- Pregnancy as determined by urinary beta-HCG test
- Illicit drug use (heroin, cocaine etc) in the past 1 year.
- Alcohol abuse, defined as the equivalent of 14 beers/week for a man or 7 beers/week for a woman
- History of allergy to DPP-4 inhibitors at the time of screening/enrollment
- Prior history of pancreatitis
- Patients currently on insulin or sulfonylurea therapy.
Patients currently on digoxin.
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Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Ciência básica
- Alocação: Randomizado
- Modelo Intervencional: Atribuição cruzada
- Mascaramento: Dobro
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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Comparador de Placebo: Matching Placebo
Matching Placebo for Sitagliptin
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Matching placebo in appearance given once/day orally
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Comparador Ativo: Sitagliptin
100mg pill, PO administered once daily.
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100 mg pill, administered once/day orally
Outros nomes:
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
---|---|---|
Brachial Artery Flow Mediated Dilation
Prazo: Change before and after a single dose (2 hours post) and 8 weeks after daily dosing
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A measurement of endothelial function in humans
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Change before and after a single dose (2 hours post) and 8 weeks after daily dosing
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Medidas de resultados secundários
Medida de resultado |
Prazo |
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Circulating Inflammatory Marker ICAM-1
Prazo: Change before and after acute dose (2 hours) and 8 weeks after daily dosing of medication
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Change before and after acute dose (2 hours) and 8 weeks after daily dosing of medication
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Circulating Inflammatory Markers VCAM-1
Prazo: Change before and after acute dose (2 hours) and 8 weeks after daily dosing of medication
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Change before and after acute dose (2 hours) and 8 weeks after daily dosing of medication
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Michael E Widlansky, MD, MPH, Medical College of Wisconsin
Publicações e links úteis
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo
Conclusão Primária (Real)
Conclusão do estudo (Real)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Estimativa)
Atualizações de registro de estudo
Última Atualização Postada (Estimativa)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Doenças cardiovasculares
- Doenças Vasculares
- Distúrbios do Metabolismo da Glicose
- Doenças Metabólicas
- Arteriosclerose
- Doenças Arteriais Oclusivas
- Doenças do Sistema Endócrino
- Diabetes Mellitus
- Aterosclerose
- Hipoglicemiantes
- Efeitos Fisiológicos das Drogas
- Mecanismos Moleculares de Ação Farmacológica
- Inibidores Enzimáticos
- Hormônios
- Hormônios, Substitutos Hormonais e Antagonistas Hormonais
- Inibidores de Protease
- Incretinas
- Inibidores de Dipeptidil-Peptidase IV
- Fosfato de Sitagliptina
Outros números de identificação do estudo
- Merck-50600
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Descrição do plano IPD
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