Angiotensin Receptors and Age Related Mitochondrial Decline in HIV Patients

HIV Clinical Trial

— RAS-HIV  

Official title:

Angiotensin Receptors and Age Related Mitochondrial Decline in HIV Patients

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02606279
• Other study ID #: WFUHS-28769
• Status: Terminated
• Phase: N/A
• Start date: July 2014
• Est. completion date: August 4, 2016

Study information

• Verified date: July 2018
• Source: Wake Forest University Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is designed to evaluate specific factors in mitochondria that may precipitate premature aging and physical weakness in HIV patients. Angiotensin receptors 1 and 2 (AT1R and AT2R) are found in virtually every cell type. This study will evaluate how the relationships among these receptors in immune and skeletal muscle cells change with HIV, and how these changes might trigger mitochondrial dysfunction, declines in muscle strength, and cellular decline in people living with HIV.

Description:

HIV related premature cellular aging and declines in mitochondrial function are closely linked. Dysfunctional mitochondria generate higher levels of reactive oxygen species (ROS) and provide less ATP supply cellular energy. Impaired turnover of damaged mitochondria leads to gradual but progressive decline in energy metabolism, increases in muscle fibrosis and clinically apparent weakness. The Renin Angiotensin System (RAS) is a central hormonal system that contributes to mitochondrial dysfunction and impacts both lifespan and function across multiple organ systems. Deletion of the angiotensin type 1 receptor (AT1R) results in a 25-30% extension of lifespan in mouse models, partly through increasing mitochondrial numbers. Blocking of AT1R reduces a number of age-related morbidities in mice, and in human studies. A plethora of data implicates RAS modulation in marked effects on fitness, frailty and beneficial responses to exercise in older adults. Despite this, there are virtually no data examining RAS biology in HIV+ vs. age-matched HIVsubjects, no data of RAS in relation to key HIV-specific variables (duration of HIV, treatment history, immune markers), and no data examining the effects of blocking AT1R on physical function in HIV infected subjects. In this study, we will examine the RAS and its contribution to premature mitochondrial failure in HIV patients. We will begin to fill this void by enrolling 40 HIV+ subjects in a randomized, double-blinded, placebo controlled pilot study of treatment with AT1R blocker to determine the feasibility of a larger trial, estimate effect size, assess the correlation of angiotensin receptor (AR) expression in peripheral blood cells and muscle cells, and the association of AR expression with physical function measures and immunity.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: August 4, 2016
• Est. primary completion date: August 4, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 60 Years

Eligibility

Inclusion Criteria:

• able to provide informed consent

• able to attend an extended (~4 hour) Clinical Research Visit

• documented HIV seropositivity

• on a stable anti-retroviral therapy (ART) regimen for at least 12 months

• HIV plasma viral load < 50 copies/ml for at least 6 months

• Systolic blood pressure >110

Exclusion Criteria:

• creatinine > 1.5 ULN (or creatinine clearance < 60 ml/min)

• anti-hypertensive therapy with ACE-I or AT1R-blockers

• inability to perform functional measures (e.g. non-ambulatory without assistance, requires a prosthesis)

• recent (within 30 days) acute illness requiring medical therapy or hospitalization

• immunosuppressive agents (e.g. > 20 mg/d x 2 or more weeks of prednisone or equivalent, chemotherapy) in the last 6 months

• cancer requiring treatment w/in 3 yrs (except for non-melanoma skin cancer)

• blood thinning medications such as Coumadin or Plavix or a bleeding disorder such as hemophilia that could cause complications during muscle biopsies

• pregnancy (will provide urine test for females of child bearing potential)

• regular use of non-steroidal anti-inflammatory drugs or other immune modulating agents.

Related Conditions & MeSH terms

• Aging
• Angiotensin Receptor Antagonists
• HIV
• Sarcopenia

Intervention

Drug:
• valsartan
Valsartan will be given in increasing doses (from 40 mg to 80 mg) to those in the valsartan arm.

Other:
• Placebo

Locations

Country	Name	City	State
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences	Johns Hopkins University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in 400m Walk	Measured by time to finish 400 meter walk	3, 6, and 9 months post-enrollment
Primary	Change From Baseline in Grip Strength	Measured by dynamometer measurement of grip strength	3, 6, and 9 months post-enrollment
Primary	Change From Baseline in Quantity of AT1R and AT2R on Monocytes	Measured by using qPCR and western blot. (Units are arbitrary units)	3, 6, and 9 months post-enrollment
Secondary	Change From Baseline in Frailty Status	Evaluated by measurements of grip strength, walking speed and questionnaires	3, 6, and 9 months post-enrollment