- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica NCT02639637
Effect of DPP4 Inhibition on Vasoconstriction
Contribution of Neuropeptide Y (NPY) to Vasoconstriction and Sympathetic Activation in the Setting of Dipeptidyl Peptidase IV (DPP4) Inhibition
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
Tipo di studio
Iscrizione (Effettivo)
Fase
- Fase 4
Contatti e Sedi
Luoghi di studio
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Tennessee
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Nashville, Tennessee, Stati Uniti, 37232
- Vanderbilt University Medical Center
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
Inclusion Criteria:
Type 2 Diabetes Mellitus, as defined by one or more of the following,
- Hgb A1C ≥6.5%, or
- Fasting plasma glucose ≥126mg/dL, or
- Two hour plasma glucose ≥200 mg/dL following 75gr oral glucose load
For female subjects the following conditions must be met:
- Postmenopausal status for at least 1 year, or
- Status post-surgical sterilization, or
- If of childbearing potential, utilization of some form of birth control and willingness to undergo β-HCG testing prior to drug treatment and on every study day
Exclusion Criteria:
- Type 1 diabetes.
- Poorly controlled T2DM, defined as Hgb A1C>8.7%.
- Use of anti-diabetic medications other than metformin.
- Hypertension.
- Subjects who have participated in a weight-reduction program during the last 6 months and whose weight has increased or decreased more than 5 kg over the preceding 6 months.
- Pregnancy. Breast-feeding.
- Treatment with any of the following drugs: cisapride, pimozide, terfenadine, astemizol
- Clinically significant gastrointestinal impairment that could interfere with drug absorption
- Cardiovascular disease that would pose risk for the subject to participate in the study, such as: myocardial infarction within 6 months prior to enrollment, presence of angina pectoris, significant arrhythmia, congestive heart failure (LV hypertrophy acceptable), deep vein thrombosis, pulmonary embolism, second- or third-degree AV block, mitral valve stenosis, or hypertrophic cardiomyopathy.
- Impaired hepatic function (aspartate amino transaminase [AST] and/or alanine amino transaminase [ALT] >2 x upper limit of normal range)
- Impaired renal function (eGFR< 60mL/min/1.73m2 as determined by the MDRD equation).
- History or presence of immunological or hematological disorders.
- History of pancreatitis or known pancreatic lesions.
- History of angioedema or cough while taking an ACE inhibitor.
- Hematocrit <35%.
- Treatment with anticoagulants.
- Growth hormone deficiency.
- Diagnosis of asthma requiring use of an inhaled β-2 agonist more than 1 time per week.
- Any underlying or acute disease requiring regular medication which could possibly pose a threat to the subject or make implementation of the protocol or interpretation of the study results difficult
- Treatment with systemic glucocorticoids within the last 6 months.
- Treatment with lithium salts
- Ongoing tobacco use or recreational drug use.
- Treatment with any investigational drug in the 1 month preceding the study
- Mental conditions rendering the subject unable to understand the nature, scope, or possible consequences of the study
- Inability to comply with the protocol, e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Scienza basilare
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione incrociata
- Mascheramento: Quadruplicare
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
---|---|
Altro: Sitagliptin then Placebo
Subjects in this arm will receive sitagliptin 100 mg daily.
After one week of treatment, subjects will report for study day #1.
During the study day subjects will be given intra-aterial neuropeptide Y and enalaprilat.
A four week washout of medications will occur after the study day.
Subjects will then receive placebo for one week followed by study day #2.
|
Subjects will receive sitagliptin 100 mg daily for 7 days prior to one of the study days.
Altri nomi:
Subjects will receive a placebo capsule daily for 7 days prior to one of the study days.
Altri nomi:
During the study days, neuropeptide Y will be infused through an intra-arterial line.
There will be four doses of neuropeptide Y used (0.1, 0.3, 1.0, and 3.0 nmol/min) and each dose will be infused for 10 minutes.
Altri nomi:
Ninety minutes after the last dose of neuropeptide Y, enalaprilat will be infused through the intra-arterial line at 0.33 µg/min/100mL of forearm volume.
After 30 minutes, a second infusion of neuropeptide Y will begin.
Similar to the previous neuropeptide infusion, four doses of neuropeptide Y will be used (0.1, 0.3, 1.0, and 3.0 nmol/min) and each dose will be infused for 10 minutes.
Altri nomi:
|
Altro: Placebo then Sitagliptin
Subjects in this arm will receive placebo for one week.
After this, subjects will report for study day #1.
During the study day subjects will be given intra-aterial neuropeptide Y and enalaprilat.
A four week washout of medications will occur after the study day.
Subjects will then receive 100 mg of sitagliptin daily for one week followed by study day #2.
|
Subjects will receive sitagliptin 100 mg daily for 7 days prior to one of the study days.
Altri nomi:
Subjects will receive a placebo capsule daily for 7 days prior to one of the study days.
Altri nomi:
During the study days, neuropeptide Y will be infused through an intra-arterial line.
There will be four doses of neuropeptide Y used (0.1, 0.3, 1.0, and 3.0 nmol/min) and each dose will be infused for 10 minutes.
Altri nomi:
Ninety minutes after the last dose of neuropeptide Y, enalaprilat will be infused through the intra-arterial line at 0.33 µg/min/100mL of forearm volume.
After 30 minutes, a second infusion of neuropeptide Y will begin.
Similar to the previous neuropeptide infusion, four doses of neuropeptide Y will be used (0.1, 0.3, 1.0, and 3.0 nmol/min) and each dose will be infused for 10 minutes.
Altri nomi:
|
Comparatore placebo: Sitagliptin then Placebo: Valsartan
Subjects in this arm will receive sitagliptin 100 mg/d for one week as well as valsartan 160 mg/d for one week.
After this subjects will report for study day #1.
During the study day, subjects will be given intra-arterial neuropeptide Y.
A four week washout of medication will occur after the study day.
Subjects will then receive placebo/d and valsartan 160 mg/d for one week followed by study day #2.
|
Subjects will receive sitagliptin 100 mg daily for 7 days prior to one of the study days.
Altri nomi:
Subjects will receive a placebo capsule daily for 7 days prior to one of the study days.
Altri nomi:
Valsartan 160 mg/d for 7 days prior to one of the study days.
Altri nomi:
|
Comparatore placebo: Placebo then Sitagliptin: Valsartan
Subjects in this arm will receive placebo/d for one week as well as valsartan 160 mg/d for one week.
After this subjects will report for study day #1.
During the study day, subjects will be given intra-arterial neuropeptide Y.
A four week washout of medication will occur after the study day.
Subjects will then receive sitagliptin 100mg/d and valsartan 160 mg/d for one week followed by study day #2.
|
Subjects will receive sitagliptin 100 mg daily for 7 days prior to one of the study days.
Altri nomi:
Subjects will receive a placebo capsule daily for 7 days prior to one of the study days.
Altri nomi:
Valsartan 160 mg/d for 7 days prior to one of the study days.
Altri nomi:
|
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
---|---|---|
Forearm Blood Flow
Lasso di tempo: FBF measured after 5 min of the 1 nmol/min dose of neuropeptide Y on study days 1 and 2. Study days 1 and two were separated by five weeks.
|
Forearm blood flow measured by strain gauge plethysmography in response to 1.0 nmol/min neuropeptide Y, the highest dose that all received.
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FBF measured after 5 min of the 1 nmol/min dose of neuropeptide Y on study days 1 and 2. Study days 1 and two were separated by five weeks.
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
---|---|---|
Arterial Norepinephrine
Lasso di tempo: Measured at baseline (time 0) prior to the infusion of neuropeptide Y on each study day. Study days 1 and 2 were separated by five weeks.
|
Arterial norepinephrine concentration measured by high-performance liquid chromatography.
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Measured at baseline (time 0) prior to the infusion of neuropeptide Y on each study day. Study days 1 and 2 were separated by five weeks.
|
Venous Norepinephrine
Lasso di tempo: Measured at baseline (time 0) prior to the infusion of neuropeptide Y on each study day. Study days 1 and 2 were separated by five weeks.
|
Venous norepinephrine concentration measured by high-performance liquid chromatography
|
Measured at baseline (time 0) prior to the infusion of neuropeptide Y on each study day. Study days 1 and 2 were separated by five weeks.
|
NPY Metabolites
Lasso di tempo: Measured after 5 min infusion of the 1.0 nmol/min dose of neuropeptide Y on study days 1 and 2. Study days 1 and 2 were separated by five weeks.
|
NPY (3-36) concentration measured by micro ultra-hgih pressure liquid chromatography tandem mass spectrometry. NPY (3-36) is the degradation product of NPY by dipeptidyl peptidase 4. It was measured only in the diabetics studied. |
Measured after 5 min infusion of the 1.0 nmol/min dose of neuropeptide Y on study days 1 and 2. Study days 1 and 2 were separated by five weeks.
|
Insulin
Lasso di tempo: Measured at baseline (time 0) of each study day prior to the infusion of neuropeptide Y. Study days 1 and 2 were separated by five weeks, a four-week washout and one-week treatment period.
|
Plasma insulin measured by radioimmunoassay.
|
Measured at baseline (time 0) of each study day prior to the infusion of neuropeptide Y. Study days 1 and 2 were separated by five weeks, a four-week washout and one-week treatment period.
|
GLP-1
Lasso di tempo: Measured at baseline (time 0) of each study day prior to the infusion of neuropeptide Y. Study days were separated by five weeks, a four-week washout and one-week treatment period.
|
GLP--1 was not analyzed as subjects were studied in the fasting state.
|
Measured at baseline (time 0) of each study day prior to the infusion of neuropeptide Y. Study days were separated by five weeks, a four-week washout and one-week treatment period.
|
Glucose
Lasso di tempo: Measured at baseline (time 0) of each study day prior to the infusion of neuropeptide Y. Study days were separated by five weeks, a four-week washout and one-week treatment period.
|
Glucose was measured by the glucose oxidase method using a YSI glucose analyzer
|
Measured at baseline (time 0) of each study day prior to the infusion of neuropeptide Y. Study days were separated by five weeks, a four-week washout and one-week treatment period.
|
ACE Activity
Lasso di tempo: Measured at baseline (time 0) of each study day prior to the infusion of neuropeptide Y. Study days were separated by five weeks, a four-week washout and one-week treatment period.
|
ACE activity was measured using a commercially available assay (Olympus AU400/AU600, Alpco Diagnotics, Salem, NH.)
The lower level of detection was 15 U/L and values below the level of detection were reported at half the level of detection.
|
Measured at baseline (time 0) of each study day prior to the infusion of neuropeptide Y. Study days were separated by five weeks, a four-week washout and one-week treatment period.
|
DPP4 Activity
Lasso di tempo: Measured at baseline (time 0) of each study day prior to the infusion of neuropeptide Y. Study days were separated by five weeks, a four-week washout and one-week treatment period.
|
DPP4 activity was measured by detection of cleavage of a colorimetric substrate.
|
Measured at baseline (time 0) of each study day prior to the infusion of neuropeptide Y. Study days were separated by five weeks, a four-week washout and one-week treatment period.
|
Low Frequency Variability of Blood Pressure Activity
Lasso di tempo: Measured at baseline (time 0) of each study day prior to the infusion of neuropeptide Y. Study days were separated by five weeks, a four-week washout and one-week treatment period.
|
Measured using the VITAL-GARD 450c monitor Ivy Biomedical Systems, Branford, CT, USA)
|
Measured at baseline (time 0) of each study day prior to the infusion of neuropeptide Y. Study days were separated by five weeks, a four-week washout and one-week treatment period.
|
Arterial tPA
Lasso di tempo: Measured at baseline (time 0) of each study day prior to the infusion of neuropeptide Y. Study days were separated by five weeks, a four-week washout and one-week treatment period.
|
Measured using an ELISA.
|
Measured at baseline (time 0) of each study day prior to the infusion of neuropeptide Y. Study days were separated by five weeks, a four-week washout and one-week treatment period.
|
Venous tPA
Lasso di tempo: Measured at baseline (time 0) of each study day prior to the infusion of neuropeptide Y. Study days were separated by five weeks, a four-week washout and one-week treatment period.
|
Measured using an ELISA.
This was measured in a few subjects.
After it was determined that there was no change in net t-PA release it was not measured in the remainder.
|
Measured at baseline (time 0) of each study day prior to the infusion of neuropeptide Y. Study days were separated by five weeks, a four-week washout and one-week treatment period.
|
Mean Arterial Pressure
Lasso di tempo: Measured at baseline (time 0) of each study day prior to the infusion of neuropeptide Y. Study days were separated by five weeks, a four-week washout and one-week treatment period.
|
Measured at baseline (time 0) of each study day prior to the infusion of neuropeptide Y. Study days were separated by five weeks, a four-week washout and one-week treatment period.
|
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Heart Rate
Lasso di tempo: Measured at baseline (time 0) of each study day prior to the infusion of neuropeptide Y. Study days were separated by five weeks, a four-week washout and one-week treatment period.
|
Measured at baseline (time 0) of each study day prior to the infusion of neuropeptide Y. Study days were separated by five weeks, a four-week washout and one-week treatment period.
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Collaboratori e investigatori
Sponsor
Studiare le date dei record
Studia le date principali
Inizio studio
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Disturbi del metabolismo del glucosio
- Malattie metaboliche
- Malattie del sistema endocrino
- Diabete mellito
- Diabete mellito, tipo 2
- Agenti ipoglicemizzanti
- Effetti fisiologici delle droghe
- Meccanismi molecolari dell'azione farmacologica
- Agenti antipertensivi
- Inibitori enzimatici
- Ormoni
- Ormoni, sostituti ormonali e antagonisti ormonali
- Inibitori della proteasi
- Incretine
- Bloccanti del recettore di tipo 1 dell'angiotensina II
- Antagonisti del recettore dell'angiotensina
- Inibitori della dipeptidil-peptidasi IV
- Inibitori dell'enzima di conversione dell'angiotensina
- Valsartan
- Enalaprilato
- Enalapril
- Sitagliptin fosfato
Altri numeri di identificazione dello studio
- 151133
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .
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