Cardiac SteatosisPhase 2NCT02629094
Cardiometabolic Effects of Eplerenone in HIV Infection
A Phase 2 study testing Inspra /Eplerenone in people with Cardiac Steatosis and Hepatic Steatosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
Background: People with human immunodeficiency virus (HIV) are at a high risk of getting visceral or deep belly fat. Visceral fat can cause health problems like heart or liver disease. Researchers want to see if a blood pressure drug can help by blocking a hormone in the body. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Cardiac Steatosis, Hepatic Steatosis
- What is being tested?
- Inspra /Eplerenone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Dec 2015to 11 Sep 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Increased waist circumference on the basis of National Cholesterol Education Program guidelines (> 102 cm in men and > 88 cm in women)
- Hepatic steatosis established by hepatic MRI greater than or equal to 5% and/or liver biopsy within the last 12 months
- HIV-infected, HIV viral load < 50 copies/mL and no change in ART regimen for at least 3 months
- Age greater than or equal to 18 and less than or equal to 75 years
- Agree to have samples stored for future research
Who cannot join
- Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m^2, serum creatinine > 1.5 mg/dL
- Serum potassium > 5.5 mEq/L, alanine aminotransferase > 2.5 times the upper limit of normal, hemoglobin (Hgb) < 11 g/dL
- Uncontrolled hypertension: systolic blood pressure greater than or equal to 160 mm Hg or diastolic blood pressure greater than or equal to 100 mm Hg
- A blood pressure < 90mmHg systolic or < 50mm Hg diastolic
- Screening EKG with a significant heart block (e.g. PR > 300 ms) or an EKG determined significant by Cardiology consult.
- Current hepatitis C infection, unless there has been a sustained virologic response for at least 12 months
Show all 20Show fewer
- Type 2 diabetes with microalbuminuria
- Current or prior steroid use within past 6 months (except short-course or single-dose administration). Stable use of inhaled or nasal steroids are allowed.
- Use of angiotensin converting enzyme (ACE) inhibitors, angiotensin reporter blockers (ARBs), potassium-sparing diuretics, and other medications that may increase the risk of hyperkalemia
- Use of potassium supplementation or other medications known to increase potassium
- Concomitant use of strong inhibitors and/or inducers ofof cytochrome P450 isozyme (CYP)3A4
- If receiving testerone, estrogen or progesterone therapy, must be on a stable dose for at least 3 months.
- Current use of growth hormone or growth hormone-releasing hormone
- Current serious viral, bacterial, or other infection (excluding HIV)
- Current active substance abuse/dependence
- Substantial history of cardiovascular disease, including prior myocardial infarction (MI), congestive heart failure, or stroke
- Contraindication to MRI
- Pregnant or planning to become pregnant
- Breastfeeding
- Any condition that, in the opinion of the PI, may substantially increase the risk of participation
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Background:
People with human immunodeficiency virus (HIV) are at a high risk of getting visceral or deep belly fat. Visceral fat can cause health problems like heart or liver disease. Researchers want to see if a blood pressure drug can help by blocking a hormone in the body.
Read more
Objective:
To see if eplerenone reduces fat stored in the heart muscle and liver in people with HIV and increased visceral fat.
Eligibility:
Adults ages 18 75 with HIV and increased waist circumference. Increased waist circumference is defined as more than 40 inches in men and more than 35 inches in women.
Design:
Participants will be screened with:
Physical exam
Medical history
Blood tests
Measurements of hips, waist, legs, arms, shoulders, and neck
Magnetic resonance imaging (MRI) scan. They will lie on a table that slides into a machine.
Electrocardiogram (EKG) to measure heart electrical activity
Transient elastography, a special ultrasound to measure liver tissue stiffness
A small piece their liver collected (optional)
Participants will have a baseline visit:
Physical exam
Medical history
Blood tests
DEXA scan to measure body fat, muscle mass, and bone density. Participants will lie on a table while a very small dose of x-rays goes through the body.
Resting energy expenditure (REE). This measures the amount of oxygen breathed in and carbon dioxide breathed out.
Participants will get a 1-week supply of eplerenone. They will take one pill per day.
Participants will have a follow-up visit 1 week later. They will have:
Physical exam
Medical history
Blood tests
23-week supply of eplerenone
Participants will have 5 more follow-up visits.
Participants will have a final study visit, repeating many of the screening and baseline tests.
Read the detailed description
HIV-infected individuals are at higher risk than uninfected people for developing cardiovascular disease. Visceral adipose tissue is also increased in HIV-infected people compared to uninfected individuals. Animal studies suggest that blockade of the mineralocorticoid receptor (MR) may have beneficial effects on cardiovascular and metabolic parameters via inhibition of adipocyte differentiation and triglyceride accumulation. We will examine the effects of the MR antagonist eplerenone (50 mg daily) on HIV-infected adults with abdominal fat accumulation in a 24-week, open-label, proof-of-concept study. Magnetic resonance imaging will be conducted at screening and the final study visit to evaluate cardiac and hepatic steatosis. We anticipate that blocking the effects of increased aldosterone secretion with eplerenone will significantly reduce intramyocardial lipid content and hepatic steatosis in this population. These effects may be accompanied by decreases in visceral adipose tissue, and improvements in dyslipidemia and inflammation, thereby improving cardiovascular health.
- Conditions
- Cardiac Steatosis, Hepatic Steatosis
- Being tested
- Inspra /Eplerenone
- Keywords
- Hepatic Steatosis, Cardiac Steatosis, Aldosterone, Eplerenone, Mineralcorticoid Receptor
- Medical subject headings
- Fatty Liver
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Inspra /EplerenoneDrug
Eplerenone is provided as 25- or 50-mg tablets that are to be taken orally. Subjects will be dosed at 25 mg daily for 1 week, and then 50 mg daily for 23 weeks. The total duration of dosing for each subject is 24 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Intervention: Eplerenone will be administered for 6 months as follows: 25 mg once daily for 1 week and then 50 mg once daily for the remainder of the study. Receives: Drug: Inspra /Eplerenone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvement of Cardiac Steatosis: Mean Change in Intraventricular Septum Percentage of Lipid by MR Spectroscopy.
Mean change in intraventricular septum percentage of lipid by MR spectroscopy. This was calculated by subtracting the baseline intraventicular septum percentage value of lipid from the week 24 intraventicular septum percentage value of lipid by MR spectroscopy.
Measured: 24 weeks
Improvement of Hepatic Steatosis: Mean Change in Hepatic Percentage of Lipid by MR Spectroscopy
Mean change in hepatic percentage of lipid by MR spectroscopy. This was calculated by subtracting the baseline hepatic percentage value of lipid from the week 24 hepatic percentage value of lipid by MR spectroscopy.
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2015 (estimated)
- Study start2 Dec 2015
- Primary completion11 Sep 2017
- Study completion11 Sep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Cardiac SteatosisStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Colleen M Hadigan, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02629094
- Sponsor's protocol ID
- 160030
- Other IDs
- 16-I-0030
- Status last verified
- Sep 2017
- First submitted
- 10 Dec 2015
- Last updated
- 17 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Triant VA, Lee H, Hadigan C, Grinspoon SK. Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease. J Clin Endocrinol Metab. 2007 Jul;92(7):2506-12. doi: 10.1210/jc.2006-2190. Epub 2007 Apr 24.
PubMed 17456578Hirata A, Maeda N, Hiuge A, Hibuse T, Fujita K, Okada T, Kihara S, Funahashi T, Shimomura I. Blockade of mineralocorticoid receptor reverses adipocyte dysfunction and insulin resistance in obese mice. Cardiovasc Res. 2009 Oct 1;84(1):164-72. doi: 10.1093/cvr/cvp191. Epub 2009 Jun 8.
PubMed 19505930Suzuki J, Iwai M, Mogi M, Oshita A, Yoshii T, Higaki J, Horiuchi M. Eplerenone with valsartan effectively reduces atherosclerotic lesion by attenuation of oxidative stress and inflammation. Arterioscler Thromb Vasc Biol. 2006 Apr;26(4):917-21. doi: 10.1161/01.ATV.0000204635.75748.0f. Epub 2006 Jan 19.
PubMed 16424347Chaudhury CS, Purdy JB, Liu CY, Morse CG, Stanley TL, Kleiner D, Hadigan C. Unanticipated increases in hepatic steatosis among human immunodeficiency virus patients receiving mineralocorticoid receptor antagonist eplerenone for non-alcoholic fatty liver disease. Liver Int. 2018 May;38(5):797-802. doi: 10.1111/liv.13734. Epub 2018 Mar 31.
PubMed 29509992
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cardiometabolic Effects of Eplerenone in HIV Infection
- ClinicalTrials.gov ID
- NCT02629094
- Acronym / sponsor ID
- 160030
- Conditions
- Cardiac Steatosis, Hepatic Steatosis
- Keywords
- Hepatic Steatosis, Cardiac Steatosis, Aldosterone, Eplerenone, Mineralcorticoid Receptor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 5 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 2 Dec 2015
- Primary completion
- 11 Sep 2017 (actual)
- Study completion
- 11 Sep 2017 (actual)
- First posted
- 14 Dec 2015 (estimated)
- Results
- Posted 17 Jul 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
People with human immunodeficiency virus (HIV) are at a high risk of getting visceral or deep belly fat. Visceral fat can cause health problems like heart or liver disease. Researchers want to see if a blood pressure drug can help by blocking a hormone in the body.
Objective:
To see if eplerenone reduces fat stored in the heart muscle and liver in people with HIV and increased visceral fat.
Eligibility:
Adults ages 18 75 with HIV and increased waist circumference. Increased waist circumference is defined as more than 40 inches in men and more than 35 inches in women.
Design:
Participants will be screened with:
Physical exam
Medical history
Blood tests
Measurements of hips, waist, legs, arms, shoulders, and neck
Magnetic resonance imaging (MRI) scan. They will lie on a table that slides into a machine.
Electrocardiogram (EKG) to measure heart electrical activity
Transient elastography, a special ultrasound to measure liver tissue stiffness
A small piece their liver collected (optional)
Participants will have a baseline visit:
Physical exam
Medical history
Blood tests
DEXA scan to measure body fat, muscle mass, and bone density. Participants will lie on a table while a very small dose of x-rays goes through the body.
Resting energy expenditure (REE). This measures the amount of oxygen breathed in and carbon dioxide breathed out.
Participants will get a 1-week supply of eplerenone. They will take one pill per day.
Participants will have a follow-up visit 1 week later. They will have:
Physical exam
Medical history
Blood tests
23-week supply of eplerenone
Participants will have 5 more follow-up visits.
Participants will have a final study visit, repeating many of the screening and baseline tests.
Detailed description
HIV-infected individuals are at higher risk than uninfected people for developing cardiovascular disease. Visceral adipose tissue is also increased in HIV-infected people compared to uninfected individuals. Animal studies suggest that blockade of the mineralocorticoid receptor (MR) may have beneficial effects on cardiovascular and metabolic parameters via inhibition of adipocyte differentiation and triglyceride accumulation. We will examine the effects of the MR antagonist eplerenone (50 mg daily) on HIV-infected adults with abdominal fat accumulation in a 24-week, open-label, proof-of-concept study. Magnetic resonance imaging will be conducted at screening and the final study visit to evaluate cardiac and hepatic steatosis. We anticipate that blocking the effects of increased aldosterone secretion with eplerenone will significantly reduce intramyocardial lipid content and hepatic steatosis in this population. These effects may be accompanied by decreases in visceral adipose tissue, and improvements in dyslipidemia and inflammation, thereby improving cardiovascular health.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: Inspra /EplerenoneIntervention: Eplerenone will be administered for 6 months as follows: 25 mg once daily for 1 week and then 50 mg once daily for the remainder of the study. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
Key exclusion criteria (20 listed)
- Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m^2, serum creatinine > 1.5 mg/dL
- Serum potassium > 5.5 mEq/L, alanine aminotransferase > 2.5 times the upper limit of normal, hemoglobin (Hgb) < 11 g/dL
- Uncontrolled hypertension: systolic blood pressure greater than or equal to 160 mm Hg or diastolic blood pressure greater than or equal to 100 mm Hg
- A blood pressure < 90mmHg systolic or < 50mm Hg diastolic
- Screening EKG with a significant heart block (e.g. PR > 300 ms) or an EKG determined significant by Cardiology consult.
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 |
|---|---|---|
| Inspra /EplerenoneEplerenone is provided as 25- or 50-mg tablets that are to be taken orally. Subjects will be dosed at 25 mg daily for 1 week, and then 50 mg daily for 23 weeks. The total duration of dosing for each subject is 24 weeks. | Drug | Treatment |
Primary outcome
Improvement of Cardiac Steatosis: Mean Change in Intraventricular Septum Percentage of Lipid by MR Spectroscopy.
Time frame: 24 weeks
Mean change in intraventricular septum percentage of lipid by MR spectroscopy. This was calculated by subtracting the baseline intraventicular septum percentage value of lipid from the week 24 intraventicular septum percentage value of lipid by MR spectroscopy.
Improvement of Hepatic Steatosis: Mean Change in Hepatic Percentage of Lipid by MR Spectroscopy
Time frame: 24 weeks
Mean change in hepatic percentage of lipid by MR spectroscopy. This was calculated by subtracting the baseline hepatic percentage value of lipid from the week 24 hepatic percentage value of lipid by MR spectroscopy.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 17456578Triant VA, Lee H, Hadigan C, Grinspoon SK. Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease. J Clin Endocrinol Metab. 2007 Jul;92(7):2506-12. doi: 10.1210/jc.2006-2190. Epub 2007 Apr 24.
- Background: PubMed 19505930Hirata A, Maeda N, Hiuge A, Hibuse T, Fujita K, Okada T, Kihara S, Funahashi T, Shimomura I. Blockade of mineralocorticoid receptor reverses adipocyte dysfunction and insulin resistance in obese mice. Cardiovasc Res. 2009 Oct 1;84(1):164-72. doi: 10.1093/cvr/cvp191. Epub 2009 Jun 8.
- Background: PubMed 16424347Suzuki J, Iwai M, Mogi M, Oshita A, Yoshii T, Higaki J, Horiuchi M. Eplerenone with valsartan effectively reduces atherosclerotic lesion by attenuation of oxidative stress and inflammation. Arterioscler Thromb Vasc Biol. 2006 Apr;26(4):917-21. doi: 10.1161/01.ATV.0000204635.75748.0f. Epub 2006 Jan 19.
- Results publication: PubMed 29509992Chaudhury CS, Purdy JB, Liu CY, Morse CG, Stanley TL, Kleiner D, Hadigan C. Unanticipated increases in hepatic steatosis among human immunodeficiency virus patients receiving mineralocorticoid receptor antagonist eplerenone for non-alcoholic fatty liver disease. Liver Int. 2018 May;38(5):797-802. doi: 10.1111/liv.13734. Epub 2018 Mar 31.
Related trials for Cardiac Steatosis
Not yet recruitingPhase 3
ELEVATE-LIVER: A Study to Test Whether Survodutide Helps Improve Heart Structure and Function in People With Overweight or Obesity and Fatty Liver Disease
Obesity, Metabolic Dysfunction-associated Steatotic Liver Disease
Active, not recruitingObservational study
Expanded Studies on the SCAPIS Stockholm Reexamination Cohort
Coronary Artery Disease, Arterial Stiffness, Blood Pressure
RecruitingPhase 1
Resmetirom in Patients With MASH and HFpEF
MASH - Metabolic Dysfunction-Associated Steatohepatitis, Heart Failure With Preserved Ejection Fraction (HFPEF)
Recruiting
NMR Metabolomics-Based Risk Assessment and Stratified Digital Health Interventions in Middle-Aged Adults (PREMAP)
Type 2 Diabetes, Coronary Heart Disease
Not yet recruitingPhase 3
Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors With Statin for ACS Patients
Acute Coronary Syndromes
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.
Colleen M Hadigan, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Inspra /Eplerenone in people with Cardiac Steatosis and Hepatic Steatosis, run by National Institute of Allergy and Infectious Diseases (NIAID) 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 5 inclusion and 20 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: stopped early, as of the sponsor's last update on 17 Jul 2018. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Jul 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Improvement of Cardiac Steatosis: Mean Change in Intraventricular Septum Percentage of Lipid by MR Spectroscopy. (time frame: 24 weeks). The study lists 2 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 NCT02629094, which also lists 4 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 17 Jul 2018.