Primary AldosteronismNCT02362308
Glucose Metabolism in Subjects With Aldosterone-Producing Adenomas
An observational study of Primary Aldosteronism, run by Vanderbilt University at 1 site in United States.
Trial summary
This observational study tests the hypothesis that endogenous aldosterone impairs insulin secretion and insulin sensitivity in subjects with primary aldosteronism. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Primary Aldosteronism
- What is being tested?
- Adrenalectomy and mineralocorticoid receptor antagonist
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2015to Jan 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ambulatory subjects, 18 to 70 years of age, inclusive
- For female subjects, the following conditions must be met:
- postmenopausal status for at least 1 year, or
- status-post surgical sterilization, or
- if of childbearing potential, utilization of adequate birth control and willingness to undergo urine beta-hcg testing on every study day.
- Primary aldosteronism determined by both:
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- Biochemical hyperaldosteronism defined as either:
- Plasma aldosterone ≥15 ng/dL
- or aldosterone-to-renin ratio of ≥30 if on ACE inhibitor
- or aldosterone-to-renin ratio of ≥40 in absence of an ACE inhibitor
- Positive suppression test defined as either:
- failure to suppress aldosterone to <7ng/dL after intravenous 0.9% saline infusion over 2 hours
- failure to suppress 24-hour urinary aldosterone excretion to <12 µcg with simultaneously documented urine sodium excretion >200 mmol.
Who cannot join
- Subjects presenting with any of the following will not be included in the study:
- Previously diagnosed type 1 Diabetes
- Type II Diabetes, as defined by ADA criteria:
- Hemoglobin A1C ≥6.5%
- Fasting plasma glucose ≥126mg/dl (7.0mmol/l)
- 2-hour 75g oral glucose tolerance test (OGTT) plasma glucose ≥200mg/dl (11.1 mmol/l) d. Current treatment with anti-diabetic medication(s)
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- Impaired renal function [estimated glomerular filtration rate (eGFR) of <30ml/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.
- Prior allergies to medications used in the study protocol (e.g. L-arginine, potassium chloride, insulin), or to drugs within the same class.
- Screening plasma potassium >5.5 mmol/L or sodium <135 mmol/L
- Cardiovascular disease such as recent (<6 months) 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
- Breast-feeding
- 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]
- Hematocrit <35%
- Any underlying or acute disease requiring regular medication which could possibly pose a threat to the subject or make implementation of the protocol or interpretation of the study results difficult, such as arthritis treated with non-steroidal antiinflammatory drugs
- Treatment with chronic systemic glucocorticoid therapy (more than 7 consecutive days in 1 month)
- Treatment with lithium salts
- History of alcohol or drug abuse
- Treatment with any investigational drug in the 1 month preceding the study
- Mental conditions rendering the subject unable to understand the nature, scope and possible consequences of the study
- Inability to comply with the protocol, e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
About this study
This observational study tests the hypothesis that endogenous aldosterone impairs insulin secretion and insulin sensitivity in subjects with primary aldosteronism.
Read the detailed description
The week of each study period, subjects will be provided a standard 160mmol/d sodium diet for 6-8 days to control for inter-individual sodium intake.
In period 1, subjects will report after 5 days of controlled sodium diet for a hyperglycemic clamp study (to measure insulin secretion). Subjects will continue the study diet, and then return for a hyperinsulinemic-euglycemic clamp study (to measure insulin sensitivity).
After completion of period 1 assessment, subjects will undergo adrenalectomy by our endocrine surgeons or initiate medical treatment, according to routine clinical care.
In period 2, the investigators will repeat the studies in the same manner as period 1, 3 to 12 months after adrenalectomy or initiation of medical treatment.
- Conditions
- Primary Aldosteronism
- Being tested
- Adrenalectomy, mineralocorticoid receptor antagonist
- Medical subject headings
- Hyperaldosteronism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AdrenalectomyOther
Adrenalectomy for treatment of primary aldosteronism, according to standard of care
mineralocorticoid receptor antagonistDrug
Also called spironolactone, eplerenone
Subjects will be treated with a mineralocorticoid receptor antagonist according to standard of care
| Study group | Role | What they receive |
|---|---|---|
| Adrenalectomy | Subjects will undergo assessment before and after adrenalectomy for treatment of primary aldosteronism Receives: Other: Adrenalectomy | |
| Medical Therapy | Subjects will undergo assessment before and after medical treatment of primary aldosteronism Receives: Drug: mineralocorticoid receptor antagonist |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Acute Glucose-stimulated Insulin Secretion
measured by hyperglycemic clamp
Measured: Change from Baseline vs. 3-12 months after intervention
Change in Insulin Sensitivity Index
measured by hyperinsulinemic-euglycemic clamp
Measured: Change from Baseline vs. 3-12 months after intervention
Change in Disposition Index (product of Insulin sensitivity index and acute insulin secretion)
Product of insulin sensitivity and insulin secretion
Measured: Change from Baseline vs. 3-12 months after intervention
Secondary outcomes (1)
Suppression of Hepatic glucose production
suppression of hepatic glucose production during hyperinsulinemic clamp, determined using glucose tracer
Measured: Change from Baseline vs. 3-12 months after intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2015 (estimated)
- Study startJan 2015
- Primary completionJan 2020
- Study completionJan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Primary AldosteronismStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University
- Sponsor type
- University, hospital or other
- Collaborators
- Brigham and Women's Hospital, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Responsible party
- Principal investigator, James Matt Luther, Vanderbilt University
- Investigators
- James M Luther, MD, Principal investigator, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02362308
- Sponsor's protocol ID
- 141553
- Other IDs
- R01DK096994
- Status last verified
- Apr 2021
- First submitted
- 5 Feb 2015
- Last updated
- 4 May 2021
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Luther JM, Wei DS, Ghoshal K, Peng D, Adler GK, Turcu AF, Nian H, Yu C, Solorzano CC, Pozzi A, Brown NJ. Treatment of Primary Aldosteronism Increases Plasma Epoxyeicosatrienoic Acids. Hypertension. 2021 Apr;77(4):1323-1331. doi: 10.1161/HYPERTENSIONAHA.120.14808. Epub 2021 Feb 15.
PubMed 33583202Adler GK, Murray GR, Turcu AF, Nian H, Yu C, Solorzano CC, Manning R, Peng D, Luther JM. Primary Aldosteronism Decreases Insulin Secretion and Increases Insulin Clearance in Humans. Hypertension. 2020 May;75(5):1251-1259. doi: 10.1161/HYPERTENSIONAHA.119.13922. Epub 2020 Mar 16.
PubMed 32172621
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Glucose Metabolism in Subjects With Aldosterone-Producing Adenomas
- ClinicalTrials.gov ID
- NCT02362308
- Acronym / sponsor ID
- 141553
- Conditions
- Primary Aldosteronism
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Vanderbilt UniversityUniversity, hospital or other
- Collaborators
- Brigham and Women's Hospital, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- Jan 2015 (actual)
- Primary completion
- Jan 2020 (actual)
- Study completion
- Jan 2020 (actual)
- First posted
- 12 Feb 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This observational study tests the hypothesis that endogenous aldosterone impairs insulin secretion and insulin sensitivity in subjects with primary aldosteronism.
Detailed description
The week of each study period, subjects will be provided a standard 160mmol/d sodium diet for 6-8 days to control for inter-individual sodium intake.
In period 1, subjects will report after 5 days of controlled sodium diet for a hyperglycemic clamp study (to measure insulin secretion). Subjects will continue the study diet, and then return for a hyperinsulinemic-euglycemic clamp study (to measure insulin sensitivity).
After completion of period 1 assessment, subjects will undergo adrenalectomy by our endocrine surgeons or initiate medical treatment, according to routine clinical care.
In period 2, the investigators will repeat the studies in the same manner as period 1, 3 to 12 months after adrenalectomy or initiation of medical treatment.
Study design
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Adrenalectomy | – | Other: AdrenalectomySubjects will undergo assessment before and after adrenalectomy for treatment of primary aldosteronism |
| Medical Therapy | – | Drug: mineralocorticoid receptor antagonistSubjects will undergo assessment before and after medical treatment of primary aldosteronism |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Ambulatory subjects, 18 to 70 years of age, inclusive
- For female subjects, the following conditions must be met:
- Primary aldosteronism determined by both:
Key exclusion criteria (25 listed)
- Subjects presenting with any of the following will not be included in the study:
- Previously diagnosed type 1 Diabetes
- Type II Diabetes, as defined by ADA criteria:
- Impaired renal function [estimated glomerular filtration rate (eGFR) of <30ml/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.
- Prior allergies to medications used in the study protocol (e.g. L-arginine, potassium chloride, insulin), or to drugs within the same class.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AdrenalectomyAdrenalectomy for treatment of primary aldosteronism, according to standard of care | Other | Adrenalectomy |
| mineralocorticoid receptor antagonistAlso: spironolactone, eplerenoneSubjects will be treated with a mineralocorticoid receptor antagonist according to standard of care | Drug | Medical Therapy |
Primary outcome
Change in Acute Glucose-stimulated Insulin Secretion
Time frame: Change from Baseline vs. 3-12 months after intervention
measured by hyperglycemic clamp
Change in Insulin Sensitivity Index
Time frame: Change from Baseline vs. 3-12 months after intervention
measured by hyperinsulinemic-euglycemic clamp
Change in Disposition Index (product of Insulin sensitivity index and acute insulin secretion)
Time frame: Change from Baseline vs. 3-12 months after intervention
Product of insulin sensitivity and insulin secretion
1 secondary outcome
Suppression of Hepatic glucose production
Time frame: Change from Baseline vs. 3-12 months after intervention
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2021.
- Results publication: PubMed 33583202Luther JM, Wei DS, Ghoshal K, Peng D, Adler GK, Turcu AF, Nian H, Yu C, Solorzano CC, Pozzi A, Brown NJ. Treatment of Primary Aldosteronism Increases Plasma Epoxyeicosatrienoic Acids. Hypertension. 2021 Apr;77(4):1323-1331. doi: 10.1161/HYPERTENSIONAHA.120.14808. Epub 2021 Feb 15.
- Results publication: PubMed 32172621Adler GK, Murray GR, Turcu AF, Nian H, Yu C, Solorzano CC, Manning R, Peng D, Luther JM. Primary Aldosteronism Decreases Insulin Secretion and Increases Insulin Clearance in Humans. Hypertension. 2020 May;75(5):1251-1259. doi: 10.1161/HYPERTENSIONAHA.119.13922. Epub 2020 Mar 16.
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Primary Aldosteronism
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James M Luther, MD principal investigator
Vanderbilt University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Primary Aldosteronism, run by Vanderbilt University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Acute Glucose-stimulated Insulin Secretion (time frame: Change from Baseline vs. 3-12 months after intervention). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02362308, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2021.