Trial Outcomes & Findings for Effect of DPP4 Inhibition on Vasoconstriction (NCT NCT02639637)
NCT ID: NCT02639637
Last Updated: 2018-08-27
Results Overview
Forearm blood flow measured by strain gauge plethysmography in response to 1.0 nmol/min neuropeptide Y, the highest dose that all received.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
18 participants
Primary outcome timeframe
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.
Results posted on
2018-08-27
Participant Flow
Participant milestones
| Measure |
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.
|
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.
|
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.
|
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.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
7
|
6
|
2
|
3
|
|
Overall Study
COMPLETED
|
7
|
6
|
2
|
3
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Effect of DPP4 Inhibition on Vasoconstriction
Baseline characteristics by cohort
| Measure |
Controls Who Completed Crossover Arm 1 or 2
n=7 Participants
Healthy non-smokers Crossover arm 1 is sitagliptin then placebo Crossover arm 2 is placebo then sitagliptin
|
Patients With Diabetes Who Completed Crossover Arm 1 or 2
n=6 Participants
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
|
Controls Who Completed Crossover Arm 3 or 4
n=5 Participants
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
|
Total
n=18 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
15 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Age, Continuous
|
33.2 years
STANDARD_DEVIATION 10.0 • n=5 Participants
|
43.6 years
STANDARD_DEVIATION 6.0 • n=7 Participants
|
31.4 years
STANDARD_DEVIATION 9.0 • n=5 Participants
|
36.2 years
STANDARD_DEVIATION 9.7 • n=4 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
7 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
18 Participants
n=4 Participants
|
|
Body mass index
|
25.9 kg/m^2
STANDARD_DEVIATION 2.7 • n=5 Participants
|
33.6 kg/m^2
STANDARD_DEVIATION 8.7 • n=7 Participants
|
25.7 kg/m^2
STANDARD_DEVIATION 2.0 • n=5 Participants
|
28.4 kg/m^2
STANDARD_DEVIATION 6.3 • n=4 Participants
|
|
Hemoglobin A1c
|
5.2 percentage of hemoglobin
STANDARD_DEVIATION 0.6 • n=5 Participants
|
6.6 percentage of hemoglobin
STANDARD_DEVIATION 0.2 • n=7 Participants
|
5.0 percentage of hemoglobin
STANDARD_DEVIATION 0.2 • n=5 Participants
|
5.6 percentage of hemoglobin
STANDARD_DEVIATION 0.8 • n=4 Participants
|
|
Fasting glucose
|
78.3 mg/dL
STANDARD_DEVIATION 12.7 • n=5 Participants
|
105.7 mg/dL
STANDARD_DEVIATION 12.7 • n=7 Participants
|
80.4 mg/dL
STANDARD_DEVIATION 4.4 • n=5 Participants
|
88.0 mg/dL
STANDARD_DEVIATION 15.3 • n=4 Participants
|
PRIMARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Placebo and Valsartan (Controls Only)
n=5 Participants
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.
|
Sitagliptin and Enalaprilat (Diabetics and Controls)
n=13 Participants
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.
|
Placebo and Enalaprilat (Diabetics and Controls)
n=13 Participants
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.
|
Sitagliptin and Valsartan (Controls Only)
n=5 Participants
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.
|
|---|---|---|---|---|
|
Forearm Blood Flow
|
1.63 mL/min/100 mL
Standard Deviation 0.85
|
1.72 mL/min/100 mL
Standard Deviation 0.93
|
2.29 mL/min/100 mL
Standard Deviation 0.93
|
1.17 mL/min/100 mL
Standard Deviation 0.21
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Placebo and Valsartan (Controls Only)
n=5 Participants
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.
|
Sitagliptin and Enalaprilat (Diabetics and Controls)
n=13 Participants
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.
|
Placebo and Enalaprilat (Diabetics and Controls)
n=13 Participants
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.
|
Sitagliptin and Valsartan (Controls Only)
n=5 Participants
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.
|
|---|---|---|---|---|
|
Arterial Norepinephrine
|
125.5 pg/mL
Standard Deviation 35.1
|
211.8 pg/mL
Standard Deviation 81.8
|
174.7 pg/mL
Standard Deviation 80.2
|
151.8 pg/mL
Standard Deviation 31.3
|
SECONDARY outcome
Timeframe: 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
Outcome measures
| Measure |
Placebo and Valsartan (Controls Only)
n=5 Participants
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.
|
Sitagliptin and Enalaprilat (Diabetics and Controls)
n=13 Participants
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.
|
Placebo and Enalaprilat (Diabetics and Controls)
n=13 Participants
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.
|
Sitagliptin and Valsartan (Controls Only)
n=5 Participants
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.
|
|---|---|---|---|---|
|
Venous Norepinephrine
|
173.1 pg/mL
Standard Deviation 65.5
|
250.6 pg/mL
Standard Deviation 192.9
|
178.3 pg/mL
Standard Deviation 85.1
|
192.6 pg/mL
Standard Deviation 88.6
|
SECONDARY outcome
Timeframe: 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.Population: 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.
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.
Outcome measures
| Measure |
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.
|
Sitagliptin and Enalaprilat (Diabetics and Controls)
n=6 Participants
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.
|
Placebo and Enalaprilat (Diabetics and Controls)
n=6 Participants
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.
|
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.
|
|---|---|---|---|---|
|
NPY Metabolites
|
—
|
749 pmol/L
Standard Deviation 562
|
1206 pmol/L
Standard Deviation 1559
|
—
|
SECONDARY outcome
Timeframe: 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.Population: 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.
Plasma insulin measured by radioimmunoassay.
Outcome measures
| Measure |
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.
|
Sitagliptin and Enalaprilat (Diabetics and Controls)
n=12 Participants
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.
|
Placebo and Enalaprilat (Diabetics and Controls)
n=11 Participants
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.
|
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.
|
|---|---|---|---|---|
|
Insulin
|
—
|
16.2 microU/mL
Standard Deviation 10.6
|
19.6 microU/mL
Standard Deviation 14.1
|
—
|
SECONDARY outcome
Timeframe: 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.Population: 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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 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
Outcome measures
| Measure |
Placebo and Valsartan (Controls Only)
n=5 Participants
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.
|
Sitagliptin and Enalaprilat (Diabetics and Controls)
n=13 Participants
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.
|
Placebo and Enalaprilat (Diabetics and Controls)
n=13 Participants
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.
|
Sitagliptin and Valsartan (Controls Only)
n=5 Participants
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.
|
|---|---|---|---|---|
|
Glucose
|
88.3 mg/dL
Standard Deviation 1.9
|
94.3 mg/dL
Standard Deviation 16.1
|
100.3 mg/dL
Standard Deviation 19.6
|
85.7 mg/dL
Standard Deviation 3.4
|
SECONDARY outcome
Timeframe: 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.Population: Was not measured during the valsartan study days.
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.
Outcome measures
| Measure |
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.
|
Sitagliptin and Enalaprilat (Diabetics and Controls)
n=13 Participants
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.
|
Placebo and Enalaprilat (Diabetics and Controls)
n=13 Participants
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.
|
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.
|
|---|---|---|---|---|
|
ACE Activity
|
—
|
7.5 U/L
Standard Deviation 0
|
7.5 U/L
Standard Deviation 0
|
—
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Placebo and Valsartan (Controls Only)
n=5 Participants
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.
|
Sitagliptin and Enalaprilat (Diabetics and Controls)
n=13 Participants
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.
|
Placebo and Enalaprilat (Diabetics and Controls)
n=13 Participants
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.
|
Sitagliptin and Valsartan (Controls Only)
n=5 Participants
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.
|
|---|---|---|---|---|
|
DPP4 Activity
|
32.55 nmol/ml/min
Standard Deviation 5.58
|
10.97 nmol/ml/min
Standard Deviation 4.47
|
21.22 nmol/ml/min
Standard Deviation 5.36
|
17.46 nmol/ml/min
Standard Deviation 7.35
|
SECONDARY outcome
Timeframe: 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)
Outcome measures
| Measure |
Placebo and Valsartan (Controls Only)
n=5 Participants
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.
|
Sitagliptin and Enalaprilat (Diabetics and Controls)
n=13 Participants
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.
|
Placebo and Enalaprilat (Diabetics and Controls)
n=13 Participants
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.
|
Sitagliptin and Valsartan (Controls Only)
n=5 Participants
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.
|
|---|---|---|---|---|
|
Low Frequency Variability of Blood Pressure Activity
|
4.27 mm Hg2
Standard Deviation 2.21
|
5.16 mm Hg2
Standard Deviation 2.54
|
5.60 mm Hg2
Standard Deviation 2.45
|
6.05 mm Hg2
Standard Deviation 4.30
|
SECONDARY outcome
Timeframe: 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.Population: 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 using an ELISA.
Outcome measures
| Measure |
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.
|
Sitagliptin and Enalaprilat (Diabetics and Controls)
n=3 Participants
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.
|
Placebo and Enalaprilat (Diabetics and Controls)
n=2 Participants
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.
|
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.
|
|---|---|---|---|---|
|
Arterial tPA
|
—
|
0.047 ng/mL
Standard Deviation 0.057
|
0.115 ng/mL
Standard Deviation 0.070
|
—
|
SECONDARY outcome
Timeframe: 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.Population: 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 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.
Outcome measures
| Measure |
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.
|
Sitagliptin and Enalaprilat (Diabetics and Controls)
n=3 Participants
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.
|
Placebo and Enalaprilat (Diabetics and Controls)
n=2 Participants
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.
|
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.
|
|---|---|---|---|---|
|
Venous tPA
|
—
|
0.030 ng/mL
Standard Deviation 0.060
|
0.110 ng/mL
Standard Deviation 0.096
|
—
|
SECONDARY outcome
Timeframe: 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.Outcome measures
| Measure |
Placebo and Valsartan (Controls Only)
n=5 Participants
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.
|
Sitagliptin and Enalaprilat (Diabetics and Controls)
n=13 Participants
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.
|
Placebo and Enalaprilat (Diabetics and Controls)
n=13 Participants
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.
|
Sitagliptin and Valsartan (Controls Only)
n=5 Participants
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.
|
|---|---|---|---|---|
|
Mean Arterial Pressure
|
74.0 mm Hg
Standard Deviation 5.7
|
79.3 mm Hg
Standard Deviation 8.0
|
81.4 mm Hg
Standard Deviation 6.5
|
75.4 mm Hg
Standard Deviation 4.2
|
SECONDARY outcome
Timeframe: 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.Outcome measures
| Measure |
Placebo and Valsartan (Controls Only)
n=5 Participants
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.
|
Sitagliptin and Enalaprilat (Diabetics and Controls)
n=13 Participants
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.
|
Placebo and Enalaprilat (Diabetics and Controls)
n=13 Participants
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.
|
Sitagliptin and Valsartan (Controls Only)
n=5 Participants
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.
|
|---|---|---|---|---|
|
Heart Rate
|
60.2 beats per minute
Standard Deviation 14.2
|
67.4 beats per minute
Standard Deviation 11.7
|
66.0 beats per minute
Standard Deviation 9.4
|
59.8 beats per minute
Standard Deviation 14.3
|
Adverse Events
Sitagliptin (Diabetics and Controls)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Placebo (Diabetics and Controls)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Sitagliptin and Valsartan (Controls Only)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Placebo and Valsartan (Controls Only)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Sitagliptin (Diabetics and Controls)
n=13 participants at risk
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.
|
Placebo (Diabetics and Controls)
n=13 participants at risk
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.
|
Sitagliptin and Valsartan (Controls Only)
n=5 participants at risk
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
|
Placebo and Valsartan (Controls Only)
n=5 participants at risk
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
|
|---|---|---|---|---|
|
Nervous system disorders
paresthesias
|
7.7%
1/13 • Number of events 1 • 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.
|
0.00%
0/13 • 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.
|
0.00%
0/5 • 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.
|
0.00%
0/5 • 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.
|
|
General disorders
Light-headedness
|
7.7%
1/13 • Number of events 1 • 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.
|
7.7%
1/13 • Number of events 1 • 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.
|
0.00%
0/5 • 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.
|
20.0%
1/5 • Number of events 1 • 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.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/13 • 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.
|
7.7%
1/13 • Number of events 1 • 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.
|
0.00%
0/5 • 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.
|
0.00%
0/5 • 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.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/13 • 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.
|
0.00%
0/13 • 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.
|
0.00%
0/5 • 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.
|
20.0%
1/5 • Number of events 1 • 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.
|
Additional Information
Nancy J. Brown, M.D., Principal Investigator
Vanderbilt University Medical Center
Phone: 6153644022
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place