Trial Outcomes & Findings for Endogenous Renin-Angiotensin-Aldosterone System and Glucose Metabolism (NCT NCT02034435)
NCT ID: NCT02034435
Last Updated: 2021-01-20
Results Overview
Hyperglycemic clamp- acute insulin response (AIR) during time 0-10 minutes
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
44 participants
Primary outcome timeframe
After 8 days of diet or drug
Results posted on
2021-01-20
Participant Flow
Participant milestones
| Measure |
Aim1-Low Sodium Then High Sodium
Subjects will be provided with a low sodium diet from the Vanderbilt Clinical Research Center that will be controlled for salt content.
Participants will be given low sodium diet (50mEq/d) and Placebo tablets for 8 days and assessments will be made, washout and then cross over to a low sodium diet (50mEq/d) plus Salt tables (150mEq) for 8days and assessments will be made.
Low Salt diet plus Placebo tablet
Low Sodium diet plus Salt tablet
|
Aim 1-High Sodium Then Low Sodium
Subjects will be provided with a diet from the Vanderbilt Clinical Research Center that will be controlled for salt content.
Participants will be given low sodium diet (50mEq/d) and Salt tables (150mEq) for 8 days and assessments will be made, washout and then cross over to a low sodium diet (50mEq/d) plus Placebo tablets for 8days and assessments will be made.
Low Salt diet plus Placebo tablet
Low Sodium diet plus Salt tablet
|
Aim2- Low Sodium Diet and Epleronone Then Amlodipine
Subjects on a low salt diet will receive Epleronone 50mg for 8 days and assessments will be made, then cross over to a low salt diet with Amlodipine 5mg for 8days and assessments will be made.
Low Salt diet plus Placebo tablet
Epleronone: 50mg daily
Amlodipine: 5mg daily
|
Aim2- Low Sodium Diet and Amlodipine Then Epleronone
Subjects on a low salt diet will receive Amlodipine 5mg for 8 days and assessments will be made, then cross over to a low salt diet with Epleronone 50mg for 8days and assessments will be made.
Low Salt diet plus Placebo tablet
Epleronone: 50mg daily
Amlodipine: 5mg daily
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
13
|
15
|
7
|
9
|
|
Overall Study
Aim 1
|
13
|
15
|
0
|
0
|
|
Overall Study
Aim 2
|
0
|
0
|
7
|
9
|
|
Overall Study
COMPLETED
|
11
|
13
|
7
|
8
|
|
Overall Study
NOT COMPLETED
|
2
|
2
|
0
|
1
|
Reasons for withdrawal
| Measure |
Aim1-Low Sodium Then High Sodium
Subjects will be provided with a low sodium diet from the Vanderbilt Clinical Research Center that will be controlled for salt content.
Participants will be given low sodium diet (50mEq/d) and Placebo tablets for 8 days and assessments will be made, washout and then cross over to a low sodium diet (50mEq/d) plus Salt tables (150mEq) for 8days and assessments will be made.
Low Salt diet plus Placebo tablet
Low Sodium diet plus Salt tablet
|
Aim 1-High Sodium Then Low Sodium
Subjects will be provided with a diet from the Vanderbilt Clinical Research Center that will be controlled for salt content.
Participants will be given low sodium diet (50mEq/d) and Salt tables (150mEq) for 8 days and assessments will be made, washout and then cross over to a low sodium diet (50mEq/d) plus Placebo tablets for 8days and assessments will be made.
Low Salt diet plus Placebo tablet
Low Sodium diet plus Salt tablet
|
Aim2- Low Sodium Diet and Epleronone Then Amlodipine
Subjects on a low salt diet will receive Epleronone 50mg for 8 days and assessments will be made, then cross over to a low salt diet with Amlodipine 5mg for 8days and assessments will be made.
Low Salt diet plus Placebo tablet
Epleronone: 50mg daily
Amlodipine: 5mg daily
|
Aim2- Low Sodium Diet and Amlodipine Then Epleronone
Subjects on a low salt diet will receive Amlodipine 5mg for 8 days and assessments will be made, then cross over to a low salt diet with Epleronone 50mg for 8days and assessments will be made.
Low Salt diet plus Placebo tablet
Epleronone: 50mg daily
Amlodipine: 5mg daily
|
|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
0
|
0
|
|
Overall Study
Illness
|
0
|
2
|
0
|
0
|
|
Overall Study
Inadequate IV access
|
1
|
0
|
0
|
1
|
Baseline Characteristics
Endogenous Renin-Angiotensin-Aldosterone System and Glucose Metabolism
Baseline characteristics by cohort
| Measure |
Aim 1
n=28 Participants
Low Sodium and High Sodium diet crossover
|
Aim 2
n=16 Participants
Eplerenone and Amlodipine crossover
|
Total
n=44 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
45 years
n=5 Participants
|
46 years
n=7 Participants
|
45 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
28 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
44 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 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
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
24 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
39 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
28 participants
n=5 Participants
|
16 participants
n=7 Participants
|
44 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: After 8 days of diet or drugPopulation: Participants with metabolic syndrome
Hyperglycemic clamp- acute insulin response (AIR) during time 0-10 minutes
Outcome measures
| Measure |
Aim 1- Low Sodium
n=28 Participants
Low Sodium diet (50mEq/d)
|
Aim 1- High Sodium
n=28 Participants
Low sodium diet (50mEq/d) plus sodium tablet (150 mEq/d)
|
Aim 2- Eplerenone
n=15 Participants
Low sodium diet (50mEq/d) plus Eplerenone
|
Aim 2- Amlodipine
n=16 Participants
Low sodium diet (50mEq/d) plus Amlodipine
|
|---|---|---|---|---|
|
Insulin Secretion
|
293.1 uU/mL*10min
Interval 186.9 to 369.4
|
234.7 uU/mL*10min
Interval 161.3 to 479.7
|
330.8 uU/mL*10min
Interval 268.2 to 481.5
|
300.4 uU/mL*10min
Interval 177.8 to 477.8
|
PRIMARY outcome
Timeframe: after 8 days of diet or medicationPopulation: Participants with metabolic syndrome
Hyperinsulinemic clamp- glucose infusion rate during insulin administration
Outcome measures
| Measure |
Aim 1- Low Sodium
n=28 Participants
Low Sodium diet (50mEq/d)
|
Aim 1- High Sodium
n=28 Participants
Low sodium diet (50mEq/d) plus sodium tablet (150 mEq/d)
|
Aim 2- Eplerenone
n=15 Participants
Low sodium diet (50mEq/d) plus Eplerenone
|
Aim 2- Amlodipine
n=16 Participants
Low sodium diet (50mEq/d) plus Amlodipine
|
|---|---|---|---|---|
|
Insulin Sensitivity
|
6.6 mg/kg/min
Interval 5.5 to 7.6
|
6.9 mg/kg/min
Interval 6.1 to 7.6
|
6.4 mg/kg/min
Interval 5.8 to 8.2
|
6.3 mg/kg/min
Interval 5.4 to 7.7
|
Adverse Events
Aim 1- Low Sodium
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Aim 1- High Sodium
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Aim 2- Eplerenone
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Aim 2- Amlodipine
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Aim 1- Low Sodium
n=28 participants at risk
Low Sodium diet (50mEq/d)
|
Aim 1- High Sodium
n=28 participants at risk
Low sodium diet (50mEq/d) plus sodium tablet (150 mEq/d)
|
Aim 2- Eplerenone
n=16 participants at risk
Low sodium diet (50mEq/d) plus Eplerenone
|
Aim 2- Amlodipine
n=16 participants at risk
Low sodium diet (50mEq/d) plus Amlodipine
|
|---|---|---|---|---|
|
Nervous system disorders
Headache
|
7.1%
2/28 • Number of events 2 • Monitoring during 1 week of intervention/drug, washout period, and during cross-over to 1 week of remaining intervention/drug. Monitoring for adverse events continued up to 2 weeks after study completion.
|
7.1%
2/28 • Number of events 2 • Monitoring during 1 week of intervention/drug, washout period, and during cross-over to 1 week of remaining intervention/drug. Monitoring for adverse events continued up to 2 weeks after study completion.
|
6.2%
1/16 • Number of events 1 • Monitoring during 1 week of intervention/drug, washout period, and during cross-over to 1 week of remaining intervention/drug. Monitoring for adverse events continued up to 2 weeks after study completion.
|
0.00%
0/16 • Monitoring during 1 week of intervention/drug, washout period, and during cross-over to 1 week of remaining intervention/drug. Monitoring for adverse events continued up to 2 weeks after study completion.
|
|
Gastrointestinal disorders
Nausea
|
3.6%
1/28 • Number of events 1 • Monitoring during 1 week of intervention/drug, washout period, and during cross-over to 1 week of remaining intervention/drug. Monitoring for adverse events continued up to 2 weeks after study completion.
|
7.1%
2/28 • Number of events 2 • Monitoring during 1 week of intervention/drug, washout period, and during cross-over to 1 week of remaining intervention/drug. Monitoring for adverse events continued up to 2 weeks after study completion.
|
6.2%
1/16 • Number of events 1 • Monitoring during 1 week of intervention/drug, washout period, and during cross-over to 1 week of remaining intervention/drug. Monitoring for adverse events continued up to 2 weeks after study completion.
|
0.00%
0/16 • Monitoring during 1 week of intervention/drug, washout period, and during cross-over to 1 week of remaining intervention/drug. Monitoring for adverse events continued up to 2 weeks after study completion.
|
|
Infections and infestations
viral illness
|
3.6%
1/28 • Number of events 1 • Monitoring during 1 week of intervention/drug, washout period, and during cross-over to 1 week of remaining intervention/drug. Monitoring for adverse events continued up to 2 weeks after study completion.
|
7.1%
2/28 • Number of events 2 • Monitoring during 1 week of intervention/drug, washout period, and during cross-over to 1 week of remaining intervention/drug. Monitoring for adverse events continued up to 2 weeks after study completion.
|
0.00%
0/16 • Monitoring during 1 week of intervention/drug, washout period, and during cross-over to 1 week of remaining intervention/drug. Monitoring for adverse events continued up to 2 weeks after study completion.
|
0.00%
0/16 • Monitoring during 1 week of intervention/drug, washout period, and during cross-over to 1 week of remaining intervention/drug. Monitoring for adverse events continued up to 2 weeks after study completion.
|
|
Musculoskeletal and connective tissue disorders
Cramp
|
0.00%
0/28 • Monitoring during 1 week of intervention/drug, washout period, and during cross-over to 1 week of remaining intervention/drug. Monitoring for adverse events continued up to 2 weeks after study completion.
|
3.6%
1/28 • Number of events 1 • Monitoring during 1 week of intervention/drug, washout period, and during cross-over to 1 week of remaining intervention/drug. Monitoring for adverse events continued up to 2 weeks after study completion.
|
0.00%
0/16 • Monitoring during 1 week of intervention/drug, washout period, and during cross-over to 1 week of remaining intervention/drug. Monitoring for adverse events continued up to 2 weeks after study completion.
|
0.00%
0/16 • Monitoring during 1 week of intervention/drug, washout period, and during cross-over to 1 week of remaining intervention/drug. Monitoring for adverse events continued up to 2 weeks after study completion.
|
|
General disorders
Dizziness/Lightheadedness
|
3.6%
1/28 • Number of events 1 • Monitoring during 1 week of intervention/drug, washout period, and during cross-over to 1 week of remaining intervention/drug. Monitoring for adverse events continued up to 2 weeks after study completion.
|
3.6%
1/28 • Number of events 1 • Monitoring during 1 week of intervention/drug, washout period, and during cross-over to 1 week of remaining intervention/drug. Monitoring for adverse events continued up to 2 weeks after study completion.
|
0.00%
0/16 • Monitoring during 1 week of intervention/drug, washout period, and during cross-over to 1 week of remaining intervention/drug. Monitoring for adverse events continued up to 2 weeks after study completion.
|
0.00%
0/16 • Monitoring during 1 week of intervention/drug, washout period, and during cross-over to 1 week of remaining intervention/drug. Monitoring for adverse events continued up to 2 weeks after study completion.
|
|
Endocrine disorders
Low glucose
|
3.6%
1/28 • Number of events 1 • Monitoring during 1 week of intervention/drug, washout period, and during cross-over to 1 week of remaining intervention/drug. Monitoring for adverse events continued up to 2 weeks after study completion.
|
3.6%
1/28 • Number of events 1 • Monitoring during 1 week of intervention/drug, washout period, and during cross-over to 1 week of remaining intervention/drug. Monitoring for adverse events continued up to 2 weeks after study completion.
|
0.00%
0/16 • Monitoring during 1 week of intervention/drug, washout period, and during cross-over to 1 week of remaining intervention/drug. Monitoring for adverse events continued up to 2 weeks after study completion.
|
0.00%
0/16 • Monitoring during 1 week of intervention/drug, washout period, and during cross-over to 1 week of remaining intervention/drug. Monitoring for adverse events continued up to 2 weeks after study completion.
|
|
Injury, poisoning and procedural complications
IV infiltration or malfunction
|
0.00%
0/28 • Monitoring during 1 week of intervention/drug, washout period, and during cross-over to 1 week of remaining intervention/drug. Monitoring for adverse events continued up to 2 weeks after study completion.
|
0.00%
0/28 • Monitoring during 1 week of intervention/drug, washout period, and during cross-over to 1 week of remaining intervention/drug. Monitoring for adverse events continued up to 2 weeks after study completion.
|
6.2%
1/16 • Number of events 1 • Monitoring during 1 week of intervention/drug, washout period, and during cross-over to 1 week of remaining intervention/drug. Monitoring for adverse events continued up to 2 weeks after study completion.
|
12.5%
2/16 • Number of events 2 • Monitoring during 1 week of intervention/drug, washout period, and during cross-over to 1 week of remaining intervention/drug. Monitoring for adverse events continued up to 2 weeks after study completion.
|
|
Nervous system disorders
numbness
|
3.6%
1/28 • Number of events 1 • Monitoring during 1 week of intervention/drug, washout period, and during cross-over to 1 week of remaining intervention/drug. Monitoring for adverse events continued up to 2 weeks after study completion.
|
0.00%
0/28 • Monitoring during 1 week of intervention/drug, washout period, and during cross-over to 1 week of remaining intervention/drug. Monitoring for adverse events continued up to 2 weeks after study completion.
|
0.00%
0/16 • Monitoring during 1 week of intervention/drug, washout period, and during cross-over to 1 week of remaining intervention/drug. Monitoring for adverse events continued up to 2 weeks after study completion.
|
0.00%
0/16 • Monitoring during 1 week of intervention/drug, washout period, and during cross-over to 1 week of remaining intervention/drug. Monitoring for adverse events continued up to 2 weeks after study completion.
|
|
Gastrointestinal disorders
discomfort with swallowing pill
|
0.00%
0/28 • Monitoring during 1 week of intervention/drug, washout period, and during cross-over to 1 week of remaining intervention/drug. Monitoring for adverse events continued up to 2 weeks after study completion.
|
3.6%
1/28 • Number of events 1 • Monitoring during 1 week of intervention/drug, washout period, and during cross-over to 1 week of remaining intervention/drug. Monitoring for adverse events continued up to 2 weeks after study completion.
|
0.00%
0/16 • Monitoring during 1 week of intervention/drug, washout period, and during cross-over to 1 week of remaining intervention/drug. Monitoring for adverse events continued up to 2 weeks after study completion.
|
0.00%
0/16 • Monitoring during 1 week of intervention/drug, washout period, and during cross-over to 1 week of remaining intervention/drug. Monitoring for adverse events continued up to 2 weeks after study completion.
|
|
Gastrointestinal disorders
Pain
|
0.00%
0/28 • Monitoring during 1 week of intervention/drug, washout period, and during cross-over to 1 week of remaining intervention/drug. Monitoring for adverse events continued up to 2 weeks after study completion.
|
0.00%
0/28 • Monitoring during 1 week of intervention/drug, washout period, and during cross-over to 1 week of remaining intervention/drug. Monitoring for adverse events continued up to 2 weeks after study completion.
|
0.00%
0/16 • Monitoring during 1 week of intervention/drug, washout period, and during cross-over to 1 week of remaining intervention/drug. Monitoring for adverse events continued up to 2 weeks after study completion.
|
6.2%
1/16 • Number of events 1 • Monitoring during 1 week of intervention/drug, washout period, and during cross-over to 1 week of remaining intervention/drug. Monitoring for adverse events continued up to 2 weeks after study completion.
|
Additional Information
Dr. James M. Luther, MD
Vanderbilt University Medical Center
Phone: (615) 936-3420
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place