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- Ensaio Clínico NCT02015299
Off taRget Effects of Linagliptin monothErapy on Arterial Stiffness in Early Diabetes (RELEASE)
Diabetes is associated with an increased risk for developing premature macrovascular complications. The process of irreversible subclinical damage to the vasculature already starts during its preceding stages. Dipeptidyl peptidase (DPP)-4 inhibitors have been shown to attenuate vascular damage in preclinical studies. Off-target effects on adipose tissue inflammation, liver steatosis and atherosclerotic plaques have been extensively documented in animal studies.
Based on these considerations the investigators hypothesize that early therapy with the DPP4 inhibitor linagliptin in subjects with treatment naive type 2 diabetes will lead to beneficial effects on arterial stiffness as measured by pulse wave velocity.
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 3
Contactos e Locais
Locais de estudo
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Groningen, Holanda, 9700 RB
- University Medical Center Groningen
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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:
- Men and women, age 30 to 70 years, AND
- Treatment naïve type 2 diabetes, as defined as t
- Fasting plasma glucose ≥ 7.0 mmol/l, OR
- Random plasma glucose ≥ 11.1 mmol/l, OR
- HbA1c ≥6,5%
- Written informed consent
- Assessable Pulse Wave Velocity measurement at screening
Exclusion Criteria:
- Current or previous use of glycemic control medications
- Type 1 diabetes
- Gestational diabetes mellitus
- Other specific types of diabetes due to other causes, e.g., genetic defects in β-cell function, genetic defects in insulin action, diseases of the exocrine pancreas (such as cystic fibrosis), and drug- or chemical-induced (such as in the treatment of HIV/AIDS or after organ transplantation)
- Uncontrolled hypertension, defined as systolic blood pressure >160 or a diastolic blood pressure >100 mmHg at screening visit
- Severe dyslipidemia indicating primary dyslipidemia, defined as total cholesterol >8 mmol/l, triglycerides >10 mmol/l of high density lipoprotein cholesterol <0.6 mmol/l
- Current use of weight loss medication or previous weight loss surgery
- History of severe gastrointestinal disease
- Clinical contraindications to DPP4-inhibitors
- Previous cardiovascular disease, defined as stable coronary artery disease or acute coronary syndrome, stroke or transient ischemic attack, peripheral artery disease
- Symptomatic heart failure, New York Heart Association (NYHA) class II-IV
- Women who are currently pregnant,planning to become pregnant,breastfeeding women, or women with child bearing potential not using appropriate contraceptive measures
- Clinically significant liver disease or hepatic function greater than 3 times upper limit of normal
- Known impaired renal function or eGFR <30 ml/min/1.73m2
- Patients who are mentally incompetent and cannot sign a Patient Informed Consent
- Current active malignancy or in the previous 6 months
- Documented HIV infection
- Use of rifampicin
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Quadruplicar
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Experimental: Linagliptin
Linagliptin 5 mg/day + lifestyle advise
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one tablet linagliptin 5 mg/day for 26 weeks
Outros nomes:
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Comparador de Placebo: Placebo
Matching placebo + lifestyle advise
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one tablet matching placebo/day for 26 weeks
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Prazo |
|---|---|
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change from baseline carotid-(right) femoral arterial Pulse Wave Velocity (PWV) at 26 weeks
Prazo: baseline, week 26
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baseline, week 26
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Secondary vascular study parameters
Prazo: baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
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baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
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Subclinical vascular inflammation (FDG PET-CT)
Prazo: 26 weeks
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Target-to-background ratios (TBRs) (18)F-fluorodeoxyglucose positron emission tomography computed tomography coregistration (FDG PET-CT)
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26 weeks
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Outras medidas de resultado
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Body Mass Index and Waist-to-Hip ratio
Prazo: baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
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Body Mass Index and Waist-to-Hip ratio
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baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
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Blood pressure
Prazo: baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
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24-hours ambulatory blood pressure measurement (24-ABPM)
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baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
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Advanced glycation end products
Prazo: baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
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Skin AGE deposition measured and plasma levels of AGEs
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baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
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plasma markers of inflammation
Prazo: baseline, week 26
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baseline, week 26
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plasma markers of endothelial dysfunction
Prazo: baseline, week 26
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baseline, week 26
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Glycemic indices
Prazo: baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
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Fasting glucose (FPG) and 2-hour post OGTT glucose (OGTT), HbA1c
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baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
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albuminuria
Prazo: baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
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Urinary albumin/creatinine ratio
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baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
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Lifestyle
Prazo: baseline, week 26
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Intake of energy, Eating behaviour, and Physical activity
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baseline, week 26
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Pieter W Kamphuisen, MD PhD, University Medical Center Groningen
Publicações e links úteis
Publicações Gerais
- Reijrink M, de Boer SA, Spoor DS, Lefrandt JD, Lambers Heerspink HJ, Boellaard R, Greuter MJ, Borra RJH, Hillebrands JL, Slart RHJA, Mulder DJ. Visceral adipose tissue volume is associated with premature atherosclerosis in early type 2 diabetes mellitus independent of traditional risk factors. Atherosclerosis. 2019 Nov;290:87-93. doi: 10.1016/j.atherosclerosis.2019.09.016. Epub 2019 Sep 25.
- de Boer SA, Hovinga-de Boer MC, Heerspink HJ, Lefrandt JD, van Roon AM, Lutgers HL, Glaudemans AW, Kamphuisen PW, Slart RH, Mulder DJ. Arterial Stiffness Is Positively Associated With 18F-fluorodeoxyglucose Positron Emission Tomography-Assessed Subclinical Vascular Inflammation in People With Early Type 2 Diabetes. Diabetes Care. 2016 Aug;39(8):1440-7. doi: 10.2337/dc16-0327. Epub 2016 Jun 8.
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
- Distúrbios do Metabolismo da Glicose
- Doenças Metabólicas
- Doenças do Sistema Endócrino
- Diabetes Mellitus
- Diabetes Mellitus, Tipo 2
- Hipoglicemiantes
- Efeitos Fisiológicos das Drogas
- Mecanismos Moleculares de Ação Farmacológica
- Inibidores Enzimáticos
- Hormônios
- Hormônios, Substitutos Hormonais e Antagonistas Hormonais
- Inibidores de Protease
- Incretinas
- Linagliptina
- Inibidores de Dipeptidil-Peptidase IV
Outros números de identificação do estudo
- NL43473.042.13
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Ensaios clínicos em Linagliptin
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EMSRecrutamentoDiabetes mellitus tipo 2Brasil
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Boehringer IngelheimConcluídoDiabetes Mellitus, Tipo 2Coréia do Sul
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Fundación para la Investigación del Hospital Clínico...Instituto de Salud Carlos III; European Union Next GenerationAtivo, não recrutandoDiabetes Mellitus tipo 2Espanha
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Brigham and Women's HospitalPatient-Centered Outcomes Research Institute; McGill University; VA Boston Healthcare...Ativo, não recrutandoDiabetes tipo 2 | Doença renal | Eventos cardiovascularesEstados Unidos