- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02606279
Angiotensin Receptors and Age Related Mitochondrial Decline in HIV Patients (RAS-HIV)
July 30, 2018 updated by: Wake Forest University Health Sciences
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.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
Detailed 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.
Study Type
Interventional
Enrollment (Actual)
1
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
North Carolina
-
Winston-Salem, North Carolina, United States, 27157
- Wake Forest University Health Sciences
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
40 years to 60 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo control
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.
|
|
Experimental: Valsartan
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.
|
Valsartan will be given in increasing doses (from 40 mg to 80 mg) to those in the valsartan arm.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in 400m Walk
Time Frame: 3, 6, and 9 months post-enrollment
|
Measured by time to finish 400 meter walk
|
3, 6, and 9 months post-enrollment
|
Change From Baseline in Grip Strength
Time Frame: 3, 6, and 9 months post-enrollment
|
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
Time Frame: 3, 6, and 9 months post-enrollment
|
Measured by using qPCR and western blot.
(Units are arbitrary units)
|
3, 6, and 9 months post-enrollment
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in Frailty Status
Time Frame: 3, 6, and 9 months post-enrollment
|
Evaluated by measurements of grip strength, walking speed and questionnaires
|
3, 6, and 9 months post-enrollment
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Katherine R Schafer, MD, Wake Forest University Health Sciences
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
July 1, 2014
Primary Completion (Actual)
August 4, 2016
Study Completion (Actual)
August 4, 2016
Study Registration Dates
First Submitted
August 31, 2015
First Submitted That Met QC Criteria
November 12, 2015
First Posted (Estimate)
November 17, 2015
Study Record Updates
Last Update Posted (Actual)
August 28, 2018
Last Update Submitted That Met QC Criteria
July 30, 2018
Last Verified
July 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Nervous System Diseases
- Neurologic Manifestations
- Neuromuscular Manifestations
- Pathological Conditions, Anatomical
- Muscular Atrophy
- Atrophy
- Sarcopenia
- Molecular Mechanisms of Pharmacological Action
- Antihypertensive Agents
- Angiotensin II Type 1 Receptor Blockers
- Angiotensin Receptor Antagonists
- Valsartan
Other Study ID Numbers
- WFUHS-28769
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on HIV
-
University of Alabama at BirminghamMobile County Health Deparment; Alabama Department of Public HealthRecruitingHIV | HIV Testing | HIV Linkage to Care | HIV TreatmentUnited States
-
ANRS, Emerging Infectious DiseasesHopital Universitaire Robert-Debre; Institut de Recherche pour le Developpement and other collaboratorsUnknownHIV | HIV-uninfected Children | Children Exposed to HIVCameroon
-
French National Agency for Research on AIDS and...Elizabeth Glaser Pediatric AIDS FoundationCompletedPartner HIV Testing | Couple HIV Counseling | Couple Communication | HIV IncidenceCameroon, Dominican Republic, Georgia, India
-
University of MinnesotaWithdrawnHIV Infections | HIV/AIDS | Hiv | AIDS | Aids/Hiv Problem | AIDS and InfectionsUnited States
-
CDC FoundationGilead SciencesUnknownHIV Preexposure Prophylaxis | HIV ChemoprophylaxisUnited States
-
Africa Health Research InstituteLondon School of Hygiene and Tropical Medicine; University College, London; University... and other collaboratorsRecruiting
-
Massachusetts General HospitalNational Institute of Mental Health (NIMH); Fenway Community Health; Tuberculosis...CompletedHIV/STI Risk | HIV/STI IncidenceUnited States, India
-
Erasmus Medical CenterNot yet recruitingHIV Infections | Hiv | HIV-1-infection | HIV I InfectionNetherlands
-
Hospital Clinic of BarcelonaCompletedIntegrase Inhibitors, HIV; HIV PROTEASE INHIBSpain
-
University of WashingtonNational Institute of Mental Health (NIMH)RecruitingHIV Prevention | HIV Preexposure Prophylaxis | ImplementationKenya
Clinical Trials on Placebo
-
SamA Pharmaceutical Co., LtdUnknownAcute Bronchitis | Acute Upper Respiratory Tract InfectionKorea, Republic of
-
National Institute on Drug Abuse (NIDA)CompletedCannabis UseUnited States
-
AstraZenecaParexel; Spandauer Damm 130; 14050; Berlin, GermanyCompletedMale Subjects With Type II Diabetes (T2DM)Germany
-
Heptares Therapeutics LimitedCompletedPharmacokinetics | Safety IssuesUnited Kingdom
-
GlaxoSmithKlineCompletedPulmonary Disease, Chronic ObstructiveUnited Kingdom, Netherlands
-
ItalfarmacoCompletedBecker Muscular DystrophyNetherlands, Italy
-
Shijiazhuang Yiling Pharmaceutical Co. LtdXuanwu Hospital, BeijingCompleted
-
GlaxoSmithKlineCompletedInfections, BacterialUnited States
-
West Penn Allegheny Health SystemCompletedAsthma | Allergic RhinitisUnited States