HIVRAS-HIVNCT02606279
Angiotensin Receptors and Age Related Mitochondrial Decline in HIV Patients
A study testing valsartan in people with HIV and Aging, run by Wake Forest University Health Sciences at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 40 to 60 years
- Conditions the study is for
- HIV, Aging, Sarcopenia
- What is being tested?
- valsartan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2014to 4 Aug 2016
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 9Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
About this study
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.
Read the 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.
- Conditions
- HIV, Aging, Sarcopenia, Angiotensin Receptor Antagonists
- Being tested
- valsartan, Placebo
- Medical subject headings
- Sarcopenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
valsartanDrug
Also called Diovan
Valsartan will be given in increasing doses (from 40 mg to 80 mg) to those in the valsartan arm.
PlaceboOther
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: valsartan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in 400m Walk
Measured by time to finish 400 meter walk
Measured: 3, 6, and 9 months post-enrollment
Change From Baseline in Grip Strength
Measured by dynamometer measurement of grip strength
Measured: 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)
Measured: 3, 6, and 9 months post-enrollment
Secondary outcomes (1)
Change From Baseline in Frailty Status
Evaluated by measurements of grip strength, walking speed and questionnaires
Measured: 3, 6, and 9 months post-enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2015 (estimated)
- Study startJul 2014
- Primary completion4 Aug 2016
- Study completion4 Aug 2016
Why it stopped: Change in study design and inability to recruit participants
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HIVStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- Johns Hopkins University
- Responsible party
- Sponsor
- Investigators
- Katherine R Schafer, MD, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02606279
- Sponsor's protocol ID
- WFUHS-28769
- Acronym
- RAS-HIV
- Status last verified
- Jul 2018
- First submitted
- 31 Aug 2015
- Last updated
- 28 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Angiotensin Receptors and Age Related Mitochondrial Decline in HIV Patients
- ClinicalTrials.gov ID
- NCT02606279
- Acronym / sponsor ID
- RAS-HIV / WFUHS-28769
- Conditions
- HIV, Aging, Sarcopenia, Angiotensin Receptor Antagonists
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Change in study design and inability to recruit participants
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Collaborators
- Johns Hopkins University
- Study start
- Jul 2014
- Primary completion
- 4 Aug 2016 (actual)
- Study completion
- 4 Aug 2016 (actual)
- First posted
- 17 Nov 2015 (estimated)
- Results
- Posted 5 Dec 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo control | Placebo comparator | Other: Placebo20 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. |
| Valsartan | Experimental | Drug: valsartan20 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. |
Who may qualify
- Ages
- 40 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| valsartanAlso: DiovanValsartan will be given in increasing doses (from 40 mg to 80 mg) to those in the valsartan arm. | Drug | Valsartan |
| Placebo | Other | Placebo control |
Primary outcome
Change From Baseline in 400m Walk
Time frame: 3, 6, and 9 months post-enrollment
Measured by time to finish 400 meter walk
Change From Baseline in Grip Strength
Time frame: 3, 6, and 9 months post-enrollment
Measured by dynamometer measurement of grip strength
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)
1 secondary outcome
Change From Baseline in Frailty Status
Time frame: 3, 6, and 9 months post-enrollment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Katherine R Schafer, MD principal investigator
Wake Forest University Health Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing valsartan in people with HIV and Aging, run by Wake Forest University Health Sciences at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Dec 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in 400m Walk (time frame: 3, 6, and 9 months post-enrollment). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2018.