Angiotensin Receptors and Age Related Mitochondrial Decline in HIV Patients

NCT02606279 | Terminated Results

• 1 other identifier: WFUHS-28769
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

HIV; Aging; Sarcopenia; Angiotensin Receptor Antagonists

Outcome Measures

Primary Outcomes (3)

• Change From Baseline in 400m Walk

  Measured by time to finish 400 meter walk

  3, 6, and 9 months post-enrollment

• Change From Baseline in Grip Strength

  Measured by dynamometer measurement of grip strength

  3, 6, and 9 months post-enrollment

• 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 Outcomes (1)

• Change From Baseline in Frailty Status

  3, 6, and 9 months post-enrollment

Study Arms (2)

Placebo control

PLACEBO COMPARATOR

20 HIV-infected participants will be randomized into a blinded arm where they will receive 24 weeks of placebo therapy. During this time, they will undergo the same study procedures as the intervention arm.

Other: Placebo

Valsartan

EXPERIMENTAL

20 HIV-infected participants will be randomized into a blinded arm where they receive 24 weeks of valsartan therapy. For those subjects randomized to the valsartan group, they will receive valsartan 40 mg by mouth daily for 2 weeks, then increase to 80 mg by mouth daily for the remaining 22 weeks. During this time, they will undergo the same study procedures as the placebo arm.

Drug: valsartan

Interventions

valsartan DRUG

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

Also known as: Diovan

Valsartan

Placebo OTHER

Placebo control

Eligibility Criteria

• Age: 40 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• Johns Hopkins University: collaborator

Study Sites (1)

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

MeSH Terms

Conditions

Sarcopenia

Interventions

Valsartan

Condition Hierarchy (Ancestors)

Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Valine; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential

Results Point of Contact

• Title: Katherine Schafer, Assistant Professor Internal Medicine
• Organization: Wake Forest University Health Sciences

kschafer@wakehealth.edu

13367166342

Study Officials

• Katherine R Schafer, MD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2015
• First Posted: November 17, 2015
• Study Start: July 1, 2014
• Primary Completion: August 4, 2016
• Study Completion: August 4, 2016
• Last Updated: August 28, 2018
• Results First Posted: December 5, 2017

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)