Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sitagliptin then Placebo | Other | 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. |
|
| Placebo then Sitagliptin | Other | 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. |
|
| Sitagliptin then Placebo: Valsartan | Placebo Comparator | 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. |
|
| Placebo then Sitagliptin: Valsartan |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sitagliptin | Drug | Subjects will receive sitagliptin 100 mg daily for 7 days prior to one of the study days. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Forearm Blood Flow | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Arterial Norepinephrine | 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 |
Not provided
Inclusion Criteria:
Type 2 Diabetes Mellitus, as defined by one or more of the following,
For female subjects the following conditions must be met:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Nancy J Brown, MD | Vanderbilt University Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Vanderbilt University Medical Center | Nashville | Tennessee | 37232 | United States |
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Sitagliptin Then Placebo (Diabetics and Controls) | 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. Neuropeptide Y: 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. Enalaprilat: 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 After 30 minutes, a second NPY at graded doses was started ten minutes after that. |
| FG001 | Placebo Then Sitagliptin (Diabetics and Controls) | 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. Neuropeptide Y: 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. Enalaprilat: 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 NPY at graded doses was started ten minutes after that. |
| FG002 | Sitagliptin Then Placebo: Valsartan (Controls Only) | 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. Sitagliptin: Subjects will receive sitagliptin 100 mg daily for 7 days prior to one of the study days. Placebo: Subjects will receive a placebo capsule daily for 7 days prior to one of the study days. Valsartan 160mg: Valsartan 160 mg/d for 7 days prior to one of the study days. |
| FG003 | Placebo Then Sitagliptin: Valsartan (Controls Only) | 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. Sitagliptin: Subjects will receive sitagliptin 100 mg daily for 7 days prior to one of the study days. Placebo: Subjects will receive a placebo capsule daily for 7 days prior to one of the study days. Valsartan 160mg: Valsartan 160 mg/d for 7 days prior to one of the study days. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
This is a crossover study with two protocols. All subjects in protocol 1 (crossover arms 1 and 2) received the same treatments, and all subjects in protocol 2 (arms 3 and 4) received the same treatments. Seven normal controls and 6 patients with diabetes completed protocol 1 (arms 1 or 2). Five normal controls completed protocol 2 (arms 3 or 4).
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Controls Who Completed Crossover Arm 1 or 2 | Healthy non-smokers Crossover arm 1 is sitagliptin then placebo Crossover arm 2 is placebo then sitagliptin |
| BG001 | Patients With Diabetes Who Completed Crossover Arm 1 or 2 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Forearm Blood Flow | Forearm blood flow measured by strain gauge plethysmography in response to 1.0 nmol/min neuropeptide Y, the highest dose that all received. | Posted | Mean | Standard Deviation | mL/min/100 mL | 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. |
|
Adverse events were assessed at each study day from consent until completion of the last study day. The total duration of the study from consent to the last study day was completed ranged from six to ten weeks.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Sitagliptin (Diabetics and Controls) | Subjects will receive sitagliptin 100 mg daily. After one week of treatment, subjects will report for a study day. During the study day subjects will be given intra-aterial neuropeptide Y and enalaprilat. Neuropeptide Y: 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. Enalaprilat: 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 After 30 minutes, a second NPY at graded doses was started ten minutes after that. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Light-headedness | General disorders | Non-systematic Assessment | Includes vasovagal symptoms |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Nancy J. Brown, M.D., Principal Investigator | Vanderbilt University Medical Center | 6153644022 | nancy.j.brown@vanderbilt.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 5, 2017 | May 3, 2018 | Prot_SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000068900 | Sitagliptin Phosphate |
| C109691 | microcrystalline cellulose |
| D009478 | Neuropeptide Y |
| D015773 | Enalaprilat |
| D000068756 | Valsartan |
| ID | Term |
|---|---|
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
Crossover Arms 1 and 2, Crossover Arms 3 and 4
Not provided
Not provided
Not provided
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. |
|
|
| Placebo | Drug | Subjects will receive a placebo capsule daily for 7 days prior to one of the study days. |
|
|
| Neuropeptide Y | Drug | 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. |
|
|
| Enalaprilat | Drug | 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. |
|
|
| Valsartan 160mg | Drug | Valsartan 160 mg/d for 7 days prior to one of the study days. |
|
|
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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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. |
Non-smokers with diabetes who were taking no medication or metformin only Crossover arm 1 is sitagliptin then placebo Crossover arm 2 is placebo then sitagliptin
| BG002 | Controls Who Completed Crossover Arm 3 or 4 | Healthy non-smokers Crossover arm 3 is sitagliptin and valsartan, then placebo and valsartan Crossover arm 4 is placebo and valsartan, then sitagliptin and valsartan |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Body mass index | Mean | Standard Deviation | kg/m^2 |
|
| Hemoglobin A1c | Mean | Standard Deviation | percentage of hemoglobin |
|
| Fasting glucose | Mean | Standard Deviation | mg/dL |
|
| OG001 | Placebo and Enalaprilat (Diabetics and Controls) | Subjects will receive placebo 100 mg daily. After one week of treatment, subjects will report for a study day. During the study day subjects will be given intra-aterial neuropeptide Y and enalaprilat. Neuropeptide Y: 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. Enalaprilat: 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 After 30 minutes, a second NPY at graded doses was started ten minutes after that. |
| OG002 | Sitagliptin and Valsartan (Controls Only) | 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 a study day. During the study day, subjects will be given intra-arterial neuropeptide Y. |
| OG003 | Placebo and Valsartan (Controls Only) | Subjects in this arm will receive a placebo for one week as well as valsartan 160 mg/d for one week. After this subjects will report for a study day. During the study day, subjects will be given intra-arterial neuropeptide Y. |
|
|
| Secondary | Arterial Norepinephrine | Arterial norepinephrine concentration measured by high-performance liquid chromatography. | Posted | Mean | Standard Deviation | pg/mL | 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. |
|
|
|
| Secondary | Venous Norepinephrine | Venous norepinephrine concentration measured by high-performance liquid chromatography | Posted | Mean | Standard Deviation | pg/mL | 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. |
|
|
|
| Secondary | NPY Metabolites | 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. | Because the purpose of measuring NPY metabolites was to assess whether sitagliptin blocks the formation of the metabolites, and because the analysis is laborious and costly, measurements were only completed in the diabetics studied. | Posted | Mean | Standard Deviation | pmol/L | 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. |
|
|
|
| Secondary | Insulin | Plasma insulin measured by radioimmunoassay. | The comparison of sitagliptin and placebo were original to the study. Because the purpose of the sitagliptin and valsartan versus placebo and valsartan comparison was to further understand the mechanism for forearm blood flow effects it was not necessary to measure insulin in that added part of the study. | Posted | Mean | Standard Deviation | microU/mL | 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. |
|
|
|
| Secondary | GLP-1 | GLP--1 was not analyzed as subjects were studied in the fasting state. | GLP--1 was not analyzed as subjects were studied in the fasting state. | Posted | 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. |
|
|
| Secondary | Glucose | Glucose was measured by the glucose oxidase method using a YSI glucose analyzer | Posted | Mean | Standard Deviation | mg/dL | 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. |
|
|
|
| Secondary | ACE Activity | 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. | Was not measured during the valsartan study days. | Posted | Mean | Standard Deviation | U/L | 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. |
|
|
|
| Secondary | DPP4 Activity | DPP4 activity was measured by detection of cleavage of a colorimetric substrate. | Posted | Mean | Standard Deviation | nmol/ml/min | 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. |
|
|
|
| Secondary | Low Frequency Variability of Blood Pressure Activity | Measured using the VITAL-GARD 450c monitor Ivy Biomedical Systems, Branford, CT, USA) | Posted | Mean | Standard Deviation | mm Hg2 | 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. |
|
|
|
| Secondary | Arterial tPA | 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. | Posted | Mean | Standard Deviation | ng/mL | 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. |
|
|
|
| Secondary | Venous tPA | 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. | 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. | Posted | Mean | Standard Deviation | ng/mL | 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. |
|
|
|
| Secondary | Mean Arterial Pressure | Posted | Mean | Standard Deviation | mm Hg | 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. |
|
|
|
| Secondary | Heart Rate | Posted | Mean | Standard Deviation | beats per minute | 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. |
|
|
|
| 0 |
| 13 |
| 0 |
| 13 |
| 2 |
| 13 |
| EG001 | Placebo (Diabetics and Controls) | Subjects will receive placebo daily. After one week of treatment, subjects will report for a study day. During the study day subjects will be given intra-aterial neuropeptide Y and enalaprilat. Neuropeptide Y: 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. Enalaprilat: 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 After 30 minutes, a second NPY at graded doses was started ten minutes after that. | 0 | 13 | 0 | 13 | 2 | 13 |
| EG002 | Sitagliptin and Valsartan (Controls Only) | 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 a study day. During the study day, subjects will be given intra-arterial neuropeptide Y | 0 | 5 | 0 | 5 | 0 | 5 |
| EG003 | Placebo and Valsartan (Controls Only) | Subjects in this arm will receive splacebo for one week as well as valsartan 160 mg/d for one week. After this subjects will report for a study day. During the study day, subjects will be given intra-arterial neuropeptide Y | 0 | 5 | 0 | 5 | 1 | 5 |
|
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| paresthesias | Nervous system disorders | Non-systematic Assessment |
|
Not provided
Not provided
Not provided
| D004700 | Endocrine System Diseases |
| D011719 |
| Pyrazines |
| D009479 | Neuropeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D009419 | Nerve Tissue Proteins |
| D011506 | Proteins |
| D004656 | Enalapril |
| D004151 | Dipeptides |
| D009842 | Oligopeptides |
| D013777 | Tetrazoles |
| D014633 | Valine |
| D000597 | Amino Acids, Branched-Chain |
| D000596 | Amino Acids |
| D000601 | Amino Acids, Essential |