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Aim 1.Test the hypothesis that activation of the endogenous renin-angiotensin-aldosterone system impairs glycemic control via effects on insulin sensitivity and insulin secretion.
Aim 2. Test the hypothesis that activation of the endogenous renin-angiotensin-aldosterone system impairs insulin secretion and insulin sensitivity via an mineralocorticoid-receptor dependent mechanism.
In aim 1 subjects are randomized to cross over between an 8 day high salt and 8 day low salt diet and assessments are made.
In aim 2, subjects are randomized to a 2x2 cross over study with an 8 day low salt diet and either eplerenone 50mg or amlodipine 5mg.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Aim1-Low Sodium then High Sodium | Active Comparator | 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. |
|
| Aim 1-high salt diet then low salt diet | Active Comparator | 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. |
|
| Aim2- low salt diet and epleronone then amlodipine | Active Comparator | 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. |
|
| aim2- low salt diet and amlodipine then epleronone | Active Comparator | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Low Salt diet plus Placebo tablet | Other |
|
| Measure | Description | Time Frame |
|---|---|---|
| Insulin Secretion | Hyperglycemic clamp- acute insulin response (AIR) during time 0-10 minutes | After 8 days of diet or drug |
| Insulin Sensitivity | Hyperinsulinemic clamp- glucose infusion rate during insulin administration | after 8 days of diet or medication |
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Inclusion Criteria:
Ambulatory subjects, 18 to 70 years of age, inclusive
For female subjects, the following conditions must be met:
Metabolic Syndrome as defined by the presence of > 3 of the following:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| James M Luther, MD | Vanderbilt University Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Vanderbilt University Medical Center | Nashville | Tennessee | 37232-6602 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | 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 |
| FG002 | 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 |
| FG003 | 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Aim 1 | Low Sodium and High Sodium diet crossover |
| BG001 | Aim 2 | Eplerenone and Amlodipine crossover |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| 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 | Insulin Secretion | Hyperglycemic clamp- acute insulin response (AIR) during time 0-10 minutes | Participants with metabolic syndrome | Posted | Median | Inter-Quartile Range | uU/mL*10min | After 8 days of diet or drug |
|
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Aim 1- Low Sodium | Low Sodium diet (50mEq/d) | 0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | Non-systematic Assessment | Headache during study |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. James M. Luther, MD | Vanderbilt University Medical Center | (615) 936-3420 | james.luther@vumc.org |
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| 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 | Oct 4, 2016 | Dec 2, 2020 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D024821 | Metabolic Syndrome |
| ID | Term |
|---|---|
| D007333 | Insulin Resistance |
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
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| ID | Term |
|---|---|
| D004039 | Diet, Sodium-Restricted |
| D012492 | Salts |
| D000077545 | Eplerenone |
| D017311 | Amlodipine |
| ID | Term |
|---|---|
| D004035 | Diet Therapy |
| D044623 | Nutrition Therapy |
| D013812 | Therapeutics |
| D004032 | Diet |
| D009747 |
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|
| Low Sodium diet plus Salt tablet | Other |
|
| Epleronone | Drug | 50mg daily |
|
|
| Amlodipine | Drug | 5mg daily |
|
|
| Illness |
|
| Inadequate IV access |
|
| BG002 |
| Total |
Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
Low sodium diet (50mEq/d) plus Eplerenone
| OG003 | Aim 2- Amlodipine | Low sodium diet (50mEq/d) plus Amlodipine |
|
|
| Primary | Insulin Sensitivity | Hyperinsulinemic clamp- glucose infusion rate during insulin administration | Participants with metabolic syndrome | Posted | Median | Inter-Quartile Range | mg/kg/min | after 8 days of diet or medication |
|
|
|
| 28 |
| 0 |
| 28 |
| 7 |
| 28 |
| EG001 | Aim 1- High Sodium | Low sodium diet (50mEq/d) plus sodium tablet (150 mEq/d) | 0 | 28 | 0 | 28 | 10 | 28 |
| EG002 | Aim 2- Eplerenone | Low sodium diet (50mEq/d) plus Eplerenone | 0 | 16 | 0 | 16 | 3 | 16 |
| EG003 | Aim 2- Amlodipine | Low sodium diet (50mEq/d) plus Amlodipine | 0 | 16 | 0 | 16 | 3 | 16 |
| Nausea | Gastrointestinal disorders | Non-systematic Assessment | Nausea |
|
| viral illness | Infections and infestations | Non-systematic Assessment | Unrelated viral or other illness |
|
| Cramp | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Dizziness/Lightheadedness | General disorders | Non-systematic Assessment |
|
| Low glucose | Endocrine disorders | Non-systematic Assessment | low glucose after clamp, resolved |
|
| IV infiltration or malfunction | Injury, poisoning and procedural complications | Non-systematic Assessment | bruising, swelling, or pain at IV site |
|
| numbness | Nervous system disorders | Non-systematic Assessment | temporary numbess in hand, resolved spontaneously |
|
| discomfort with swallowing pill | Gastrointestinal disorders | Non-systematic Assessment | temporary discomfort when swallowing tablets |
|
| Pain | Gastrointestinal disorders | Non-systematic Assessment | rectal fissure |
|
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| D009750 |
| Nutritional and Metabolic Diseases |
| Nutritional Physiological Phenomena |
| D000066888 | Diet, Food, and Nutrition |
| D010829 | Physiological Phenomena |
| D007287 | Inorganic Chemicals |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
| D011283 | Pregnenes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D004095 | Dihydropyridines |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |