Aldosterone and Glucose Homeostasis

NCT00732160 | Completed Results DMC

• 1 other identifier: 080248
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

Determine the effect of aldosterone on how the body handles glucose (sugar).

Conditions

Diabetes Mellitus

Keywords

Glucose; Insulin

Outcome Measures

Primary Outcomes (1)

• Insulin Secretion

  Acute Insulin response during Hyperglycemic clamp (delta insulin uU/mL, t=0-10)

  3 hours

Secondary Outcomes (1)

• Insulin Sensitivity

  3 hours

Study Arms (4)

HS-V/A; LS-V/A

EXPERIMENTAL

High Sodium diet- Vehicle infusion then Aldosterone infusion Low Sodium diet- Vehicle infusion then Aldosterone infusion

Drug: Aldosterone infusion (A); Drug: Vehicle Infusion (V); Other: High Sodium Diet (HS); Other: Low Sodium Diet (LS)

HS-A/V; LS-A/V

EXPERIMENTAL

High Sodium diet- Aldosterone infusion then Vehicle infusion Low Sodium diet- Aldosterone infusion then Vehicle infusion

Drug: Aldosterone infusion (A); Drug: Vehicle Infusion (V); Other: High Sodium Diet (HS); Other: Low Sodium Diet (LS)

LS-V/A; HS-V/A

EXPERIMENTAL

Low Sodium diet- Vehicle infusion then Aldosterone infusion High Sodium diet- Vehicle infusion then Aldosterone infusion

Drug: Aldosterone infusion (A); Drug: Vehicle Infusion (V); Other: High Sodium Diet (HS); Other: Low Sodium Diet (LS)

LS-A/V; HS-A/V

EXPERIMENTAL

Low Sodium diet- Aldosterone infusion then Vehicle infusion High Sodium diet- Aldosterone infusion then Vehicle infusion

Drug: Aldosterone infusion (A); Drug: Vehicle Infusion (V); Other: High Sodium Diet (HS); Other: Low Sodium Diet (LS)

Interventions

Aldosterone infusion (A) DRUG

Infusion of exogenous aldosterone (0.7 mcg/kg/hr for 12.5 hrs)

Also known as: placebo

HS-A/V; LS-A/V; HS-V/A; LS-V/A; LS-A/V; HS-A/V; LS-V/A; HS-V/A

Vehicle Infusion (V) DRUG

Vehicle infusion for 12.5 hours

HS-A/V; LS-A/V; HS-V/A; LS-V/A; LS-A/V; HS-A/V; LS-V/A; HS-V/A

High Sodium Diet (HS) OTHER

160 mmol/d sodium diet for 7 days

HS-A/V; LS-A/V; HS-V/A; LS-V/A; LS-A/V; HS-A/V; LS-V/A; HS-V/A

Low Sodium Diet (LS) OTHER

20 mmol/d sodium diet for 9 days

HS-A/V; LS-A/V; HS-V/A; LS-V/A; LS-A/V; HS-A/V; LS-V/A; HS-V/A

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ambulatory subjects, 18 to 70 years of age, inclusive
• For female subjects, the following conditions must be met:
• a postmenopausal status for at least 1 year, or b status-post surgical sterilization, or c if of childbearing potential, utilization of adequate birth control and willingness to undergo urine beta-hcg testing prior to drug treatment and on every study day
• Metabolic Syndrome as defined by the presence of \> 3 of the following:
• a Systolic Blood Pressure \> 130 mm Hg OR Diastolic Blood Pressure \> 85 mm Hg. b Glucose Intolerance (Fasting Plasma Glucose \> 100 mg/dL) c Increased triglyceride level \> 150mg/dL (1.7mmol/L) d Decreased levels of HDL cholesterol For males, less than 40 mg/dL For females, less than 50 mg/dL e Waist circumference For males, greater than 40 inches (102 cm) For females, greater than 35 inches (89 cm).

You may not qualify if:

• Previously diagnosed Type I Diabetes , or the use of anti-diabetic medication. Subjects with type II diabetes not on medication will be allowed to participate if fasting blood glucose is \<200mg/dL.
• Prior allergies to medications used in the study protocol (e.g. L-arginine, potassium chloride).
• Screening plasma potassium \<3.5 mmol/L or use of chronic potassium supplements for the treatment of hypokalemia
• Use of hormone replacement therapy
• If on statin therapy for hypercholesterolemia, a change in dose within the past 6 months.
• Breast-feeding
• Cardiovascular disease such as prior myocardial infarction, presence of angina pectoris, significant arrhythmia, congestive heart failure (LV hypertrophy acceptable), deep vein thrombosis, pulmonary embolism, second or third degree heart block, mitral valve stenosis, aortic stenosis or hypertrophic cardiomyopathy
• Treatment with anticoagulants
• History of serious neurologic disease such as cerebral hemorrhage, stroke, seizure, or transient ischemic attack
• History or presence of immunological or hematological disorders
• Diagnosis of asthma requiring use of inhaled beta agonist \>1 time per week
• Clinically significant gastrointestinal impairment that could interfere with drug absorption
• Impaired hepatic function \[aspartate amino transaminase (AST) and/or alanine amino transaminase (ALT) \>2.0 x upper limit of normal range\]
• Impaired renal function \[estimated glomerular filtration rate (eGFR) of \<60ml/min\] as determined by the four-variable Modification of Diet in Renal Disease (MDRD) equation, where serum creatinine (Scr) is expressed in mg/dl and age in years:
• eGFR \<60 ml/min

Sponsors & Collaborators

• Vanderbilt University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (3)

• Ramirez CE, Shuey MM, Milne GL, Gilbert K, Hui N, Yu C, Luther JM, Brown NJ. Arg287Gln variant of EPHX2 and epoxyeicosatrienoic acids are associated with insulin sensitivity in humans. Prostaglandins Other Lipid Mediat. 2014 Oct;113-115:38-44. doi: 10.1016/j.prostaglandins.2014.08.001. Epub 2014 Aug 28.

  PMID: 25173047 DERIVED

• Luther JM, Byrne LM, Yu C, Wang TJ, Brown NJ. Dietary sodium restriction decreases insulin secretion without affecting insulin sensitivity in humans. J Clin Endocrinol Metab. 2014 Oct;99(10):E1895-902. doi: 10.1210/jc.2014-2122. Epub 2014 Jul 16.

  PMID: 25029426 DERIVED

• Brown JM, Williams JS, Luther JM, Garg R, Garza AE, Pojoga LH, Ruan DT, Williams GH, Adler GK, Vaidya A. Human interventions to characterize novel relationships between the renin-angiotensin-aldosterone system and parathyroid hormone. Hypertension. 2014 Feb;63(2):273-80. doi: 10.1161/HYPERTENSIONAHA.113.01910. Epub 2013 Nov 4.

  PMID: 24191286 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus; Insulin Resistance

Interventions

Diet, Sodium-Restricted

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Results Point of Contact

• Title: James M. Luther
• Organization: Vanderbilt University Medical Center

James.Luther@Vanderbilt.edu

(615) 936-3420

Study Officials

• James M Luther, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: August 5, 2008
• First Posted: August 11, 2008
• Study Start: September 1, 2008
• Primary Completion: September 1, 2012
• Study Completion: December 1, 2013
• Last Updated: April 6, 2017
• Results First Posted: April 6, 2017

Record last verified: 2017-02

Locations

US (1)