Physiologic Investigation of the Renin Angiotensin Aldosterone Axis in HIV

NCT01407237 | Completed

• 1 other identifier: 2011P000250
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV-infection

Keywords

HIV-infection; renin; aldosterone; visceral fat

Outcome Measures

Primary Outcomes (1)

• 24-hour urine aldosterone to creatinine ratio

  baseline

Secondary Outcomes (6)

• Plasma Renin Activity

  baseline

• Aldosterone response to Angiotensin II Infusion

  baseline

• Flow mediated dilation

  baseline

• Intramyocellular Lipid

  baseline

• Hepatic fat

  baseline

Study Arms (2)

HIV-infected Individuals

Drug: Angiotensin II Infusion

non-HIV-infected Individuals

Drug: Angiotensin II Infusion

Interventions

Angiotensin II Infusion DRUG

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.

HIV-infected Individuals; non-HIV-infected Individuals

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

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

You may not qualify if:

• 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
• Current or recent steroid use within last 2 months.
• Known diabetes and/or use of antidiabetic medications
• Creatinine \> 1.5 mg/dL
• Potassium (K) \> 5.5 mEq/L
• Hemoglobin (Hgb) \< 11.0 mg/dL
• Alanine aminotransferase (ALT) \> 2.5 x upper limit of normal (ULN)
• Thyroid disease/abnormal thyroid stimulating hormone (TSH)
• Significant electrocardiographic abnormalities at screen such as heart block or ischemia
• History of congestive heart failure, stroke, myocardial infarction, or known coronary artery disease (CAD)
• For women: Pregnant or actively seeking pregnancy, or breastfeeding
• Estrogen, progestational derivative, growth hormone (GH), growth hormone releasing hormone (GHRH) or ketoconazole use within 3 months.
• Current viral, bacterial or other infections (excluding HIV)
• Current cigarette smoker/use of nicotine (patch/gum) or current active substance abuse

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (5)

• Bogorodskaya M, Fitch KV, Burdo TH, Maehler P, Easly RM, Murray GR, Feldpausch M, Adler GK, Grinspoon SK, Srinivasa S. Serum Lipocalin 2 (Neutrophil Gelatinase-Associated Lipocalin) in Relation to Biomarkers of Inflammation and Cardiac Stretch During Activation of the Renin-Angiotensin-Aldosterone System in Human Immunodeficiency Virus. J Infect Dis. 2019 Sep 26;220(9):1420-1424. doi: 10.1093/infdis/jiz346.

  PMID: 31298286 DERIVED

• Murphy CA, Fitch KV, Feldpausch M, Maehler P, Wong K, Torriani M, Adler GK, Grinspoon SK, Srinivasa S. Excessive Adiposity and Metabolic Dysfunction Relate to Reduced Natriuretic Peptide During RAAS Activation in HIV. J Clin Endocrinol Metab. 2018 Apr 1;103(4):1558-1565. doi: 10.1210/jc.2017-02198.

  PMID: 29408981 DERIVED

• O'Malley TK, Burdo TH, Robinson JA, Fitch KV, Grinspoon SK, Srinivasa S. Acute hyperinsulinemia effects on systemic markers of immune activation in HIV. AIDS. 2017 Jul 31;31(12):1771-1773. doi: 10.1097/QAD.0000000000001545.

  PMID: 28514281 DERIVED

• 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. doi: 10.1093/infdis/jiw392. Epub 2016 Aug 22.

  PMID: 27549584 DERIVED

• 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.

  PMID: 26086328 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 27, 2011
• First Posted: August 2, 2011
• Study Start: January 1, 2012
• Primary Completion: March 1, 2015
• Last Updated: August 5, 2016

Record last verified: 2016-08

Locations

US (1)