Physiologic Investigation of the Renin Angiotensin Aldosterone Axis in HIV

Study Description

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

The purpose of this study is to see if individuals with HIV-infection, particularly those with increased belly fat, have abnormalities in the renin angiotensin aldosterone axis. Renin, angiotensin, and aldosterone are hormones that regulate salt and water balance in the body, and they may also have effects on sugar metabolism and cardiovascular health. There is some evidence that individuals with HIV-associated abdominal fat accumulation may have increased aldosterone, which may contribute to abnormalities in sugar metabolism and increased cardiovascular disease seen in HIV. The purpose of this study is the measure renin, angiotensin, and aldosterone activity, as well as other hormonal axes, in people with and without HIV infection, and with and without increased belly fat. The investigators hypothesize that aldosterone will be increased in HIV-infected individuals compared to those without HIV-infection, and that aldosterone will be further increased in HIV-infected individuals with increased abdominal fat compared to those without abdominal fat accumulation.

Condition or disease	Intervention/treatment
HIV-infection	Drug: Angiotensin II Infusion

Study Design

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Study Type :	Observational
Actual Enrollment :	30 participants
Observational Model:	Cohort
Time Perspective:	Cross-Sectional
Official Title:	Physiologic Investigation of the Renin Angiotensin Aldosterone Axis in HIV
Study Start Date :	January 2012
Actual Primary Completion Date :	March 2015

Groups and Cohorts

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Group/Cohort	Intervention/treatment
HIV-infected Individuals	Drug: Angiotensin II Infusion; Angiotensin II (Bachem) will be infused at 0.3 ng/kg/min for 30 minutes, then 1.0 ng/kg/min for 30 minutes, then 3.0 ng/kg/min for 30 minutes; at baseline and at each infusion concentration, serum aldosterone will be measured. BP and heart rate will be monitored at baseline and every 2 minutes during the infusion.
non-HIV-infected Individuals	Drug: Angiotensin II Infusion; Angiotensin II (Bachem) will be infused at 0.3 ng/kg/min for 30 minutes, then 1.0 ng/kg/min for 30 minutes, then 3.0 ng/kg/min for 30 minutes; at baseline and at each infusion concentration, serum aldosterone will be measured. BP and heart rate will be monitored at baseline and every 2 minutes during the infusion.

Outcome Measures

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. 24-hour urine aldosterone to creatinine ratio [ Time Frame: baseline ]

Secondary Outcome Measures :

1. Plasma Renin Activity [ Time Frame: baseline ]
2. Aldosterone response to Angiotensin II Infusion [ Time Frame: baseline ]
3. Flow mediated dilation [ Time Frame: baseline ]
4. Intramyocellular Lipid [ Time Frame: baseline ]
5. Hepatic fat [ Time Frame: baseline ]
6. Insulin stimulated glucose uptake [ Time Frame: baseline ]

Eligibility Criteria

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	18 Years to 65 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes
Sampling Method:	Non-Probability Sample

Study Population

50 HIV-infected and 50 non-HIV-infected male and female volunteers, ages 18-65 years old.

Criteria

Inclusion Criteria:

1. Stable use of antiretroviral therapy for at least 3 months (HIV group)
2. Age ≥ 18 and ≤ 65 years of age

Exclusion Criteria:

1. Antihypertensive use, including angiotensin converting enzyme inhibitors or angiotensin II receptor blocker use, diuretics, beta-blockers, calcium-channel blockers, potassium supplements, and spironolactone; and/or blood pressure (BP) >140/90 at screen
2. Current or recent steroid use within last 2 months.
3. Known diabetes and/or use of antidiabetic medications
4. Creatinine > 1.5 mg/dL
5. Potassium (K) > 5.5 mEq/L
6. Hemoglobin (Hgb) < 11.0 mg/dL
7. Alanine aminotransferase (ALT) > 2.5 x upper limit of normal (ULN)
8. Thyroid disease/abnormal thyroid stimulating hormone (TSH)
9. Significant electrocardiographic abnormalities at screen such as heart block or ischemia
10. History of congestive heart failure, stroke, myocardial infarction, or known coronary artery disease (CAD)
11. For women: Pregnant or actively seeking pregnancy, or breastfeeding
12. Estrogen, progestational derivative, growth hormone (GH), growth hormone releasing hormone (GHRH) or ketoconazole use within 3 months.
13. Current viral, bacterial or other infections (excluding HIV)
14. Current cigarette smoker/use of nicotine (patch/gum) or current active substance abuse

Contacts and Locations

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114

Sponsors and Collaborators

Massachusetts General Hospital

More Information

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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Srinivasa S, Burdo TH, Williams KC, Mitten EK, Wong K, Fitch KV, Stanley T, Adler GK, Grinspoon SK. Effects of Sodium Restriction on Activation of the Renin-Angiotensin-Aldosterone System and Immune Indices During HIV Infection. J Infect Dis. 2016 Nov 1;214(9):1336-1340. Epub 2016 Aug 22.

Srinivasa S, Fitch KV, Wong K, Torriani M, Mayhew C, Stanley T, Lo J, Adler GK, Grinspoon SK. RAAS Activation Is Associated With Visceral Adiposity and Insulin Resistance Among HIV-infected Patients. J Clin Endocrinol Metab. 2015 Aug;100(8):2873-82. doi: 10.1210/jc.2015-1461. Epub 2015 Jun 18.

Responsible Party:	Steven K. Grinspoon, MD, Principal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier:	NCT01407237 History of Changes
Other Study ID Numbers:	2011P000250
First Posted:	August 2, 2011
Last Update Posted:	August 5, 2016
Last Verified:	August 2016

Keywords provided by Steven K. Grinspoon, MD, Massachusetts General Hospital:

HIV-infection; renin; aldosterone; visceral fat

Additional relevant MeSH terms:

HIV Infections; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Immunologic Deficiency Syndromes	Immune System Diseases; Angiotensin II; Angiotensinogen; Vasoconstrictor Agents; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action