- ICH GCP
- US-Register für klinische Studien
- Klinische Studie NCT02639637
Effect of DPP4 Inhibition on Vasoconstriction
27. Juli 2018 aktualisiert von: Nancy J. Brown, MD, Vanderbilt University
Contribution of Neuropeptide Y (NPY) to Vasoconstriction and Sympathetic Activation in the Setting of Dipeptidyl Peptidase IV (DPP4) Inhibition
The purpose of this study is to understand how dipeptidyl peptidase IV (DPP4) inhibition in diabetics affects hemodynamic parameters and sympathetic activation in the setting of increasing concentrations of neuropeptide Y, an endogenous peptide.
The central hypothesis is that DPP4 inhibition decreases degradation of neuropeptide Y, resulting in increased vasoconstriction and sympathetic activation.
Studienübersicht
Status
Abgeschlossen
Bedingungen
Detaillierte Beschreibung
Dipeptidyl peptidase IV (DPP4) inhibitors are routinely used for the treatment of type II diabetes mellitus (T2DM).
Since the prevalence of hypertension is 1.5-3 times greater in diabetics compared to sex-aged matched controls, the use of antihypertensives such as ACE inhibitors is also common in diabetics.
DPP4 is involved in the degradation of multiple vasoactive peptides, one of which is neuropeptide Y.
This peptide is thought to play a role in blood pressure regulation and sympathetic nervous system activation.
The aim of this study is to investigate how DPP4 inhibition affects vasoconstriction in response to increasing neuropeptide Y concentrations.
Additionally, the investigators want to understand how the combination of DPP4 inhibition and ACE inhibition affects vasoconstriction and sympathetic activation.
Understanding the hemodynamic and neurohumoral changes associated with DPP4 and ACE inhibitors has important implications for the millions of patients with T2DM who take these drugs concurrently.
Studientyp
Interventionell
Einschreibung (Tatsächlich)
18
Phase
- Phase 4
Kontakte und Standorte
Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.
Studienorte
-
-
Tennessee
-
Nashville, Tennessee, Vereinigte Staaten, 37232
- Vanderbilt University Medical Center
-
-
Teilnahmekriterien
Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.
Zulassungskriterien
Studienberechtigtes Alter
18 Jahre bis 55 Jahre (Erwachsene)
Akzeptiert gesunde Freiwillige
Nein
Studienberechtigte Geschlechter
Alle
Beschreibung
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
Studienplan
Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Grundlegende Wissenschaft
- Zuteilung: Zufällig
- Interventionsmodell: Crossover-Aufgabe
- Maskierung: Vervierfachen
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
---|---|
Sonstiges: 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.
Andere Namen:
Subjects will receive a placebo capsule daily for 7 days prior to one of the study days.
Andere Namen:
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.
Andere Namen:
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.
Andere Namen:
|
Sonstiges: 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.
Andere Namen:
Subjects will receive a placebo capsule daily for 7 days prior to one of the study days.
Andere Namen:
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.
Andere Namen:
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.
Andere Namen:
|
Placebo-Komparator: 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.
Andere Namen:
Subjects will receive a placebo capsule daily for 7 days prior to one of the study days.
Andere Namen:
Valsartan 160 mg/d for 7 days prior to one of the study days.
Andere Namen:
|
Placebo-Komparator: 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.
Andere Namen:
Subjects will receive a placebo capsule daily for 7 days prior to one of the study days.
Andere Namen:
Valsartan 160 mg/d for 7 days prior to one of the study days.
Andere Namen:
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
---|---|---|
Forearm Blood Flow
Zeitfenster: 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.
|
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.
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
---|---|---|
Arterial Norepinephrine
Zeitfenster: 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.
|
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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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.
|
|
Heart Rate
Zeitfenster: 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.
|
Mitarbeiter und Ermittler
Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.
Sponsor
Studienaufzeichnungsdaten
Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.
Haupttermine studieren
Studienbeginn
1. Dezember 2015
Primärer Abschluss (Tatsächlich)
1. Juni 2017
Studienabschluss (Tatsächlich)
1. September 2017
Studienanmeldedaten
Zuerst eingereicht
16. Dezember 2015
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
20. Dezember 2015
Zuerst gepostet (Schätzen)
24. Dezember 2015
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
27. August 2018
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
27. Juli 2018
Zuletzt verifiziert
1. Juli 2018
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
- Störungen des Glukosestoffwechsels
- Stoffwechselerkrankungen
- Erkrankungen des endokrinen Systems
- Diabetes Mellitus
- Diabetes mellitus, Typ 2
- Hypoglykämische Mittel
- Physiologische Wirkungen von Arzneimitteln
- Molekulare Mechanismen der pharmakologischen Wirkung
- Antihypertensive Mittel
- Enzym-Inhibitoren
- Hormone
- Hormone, Hormonersatzstoffe und Hormonantagonisten
- Protease-Inhibitoren
- Inkretine
- Angiotensin-II-Typ-1-Rezeptorblocker
- Angiotensin-Rezeptor-Antagonisten
- Dipeptidyl-Peptidase IV-Inhibitoren
- Angiotensin-Converting-Enzym-Inhibitoren
- Valsartan
- Enalaprilat
- Enalapril
- Sitagliptinphosphat
Andere Studien-ID-Nummern
- 151133
Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .
Klinische Studien zur Typ 2 Diabetes mellitus
-
SanofiAbgeschlossenDiabetes mellitus Typ 1 – Diabetes mellitus Typ 2Ungarn, Russische Föderation, Deutschland, Polen, Japan, Vereinigte Staaten, Finnland
-
University Hospital Inselspital, BerneAbgeschlossen
-
US Department of Veterans AffairsAmerican Diabetes AssociationAbgeschlossenTyp 2 Diabetes mellitusVereinigte Staaten
-
AstraZenecaRekrutierung
-
Daewoong Pharmaceutical Co. LTD.Noch keine RekrutierungT2DM (Typ-2-Diabetes mellitus)
-
Zhongda HospitalRekrutierungTyp-2-Diabetes mellitus (T2DM)China
-
Newsoara Biopharma Co., Ltd.RekrutierungT2DM (Typ-2-Diabetes mellitus)China
-
Shanghai Golden Leaf MedTec Co. LtdAktiv, nicht rekrutierendTyp-2-Diabetes mellitus (T2DM)China
-
SanofiAbgeschlossen
-
Haisco Pharmaceutical Group Co., Ltd.AbgeschlossenT2DM (Typ-2-Diabetes mellitus)China
Klinische Studien zur Sitagliptin
-
Shahid Beheshti University of Medical SciencesIsfahan University of Medical SciencesAbgeschlossen
-
University Hospital Inselspital, BerneFresenius KabiAbgeschlossen
-
Emory UniversityMerck Sharp & Dohme LLCBeendet
-
Lundquist Institute for Biomedical Innovation at...Emmaus Medical, Inc.Beendet
-
Baylor College of MedicineNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)AbgeschlossenDiabetes Typ 1Vereinigte Staaten
-
Istanbul UniversityNestléAbgeschlossen
-
Beijing Tongren HospitalAbgeschlossen
-
University of ArkansasUniversity Hospital, Geneva; Université de MontréalBeendetHepatische Enzephalopathie | Zirrhose | Feuerfester Aszites | Hepatischer HydrothoraxVereinigte Staaten, Kanada, Schweiz
-
NovartisDaiichi Sankyo Co., Ltd.Abgeschlossen
-
Novartis PharmaceuticalsAbgeschlossen