Human Immunodeficiency VirusPhase 3VALIANT PilotNCT01176409
Can Valacyclovir Attenuate Inflammation in Antiretroviral-Treated HIV-Infected Individuals With Herpes Simplex Virus Type 2?
A Phase 3 study testing Valacyclovir in people with Human Immunodeficiency Virus and Herpes Simplex, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
The purpose of this study is to compare the levels of immune and inflammatory markers among HIV-1, HSV-2 co-infected adults achieving plasma HIV RNA suppression to <50 copies/mL, between those randomized to valacyclovir and placebo, over a twelve-week intervention period. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Human Immunodeficiency Virus, Herpes Simplex
- What is being tested?
- Valacyclovir
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteCanada
- Study dates
- Sep 2010to Aug 2013
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- adult (aged 18 years or older)
- documented HIV-1 infection (determined by EIA and Western blot)
- documented HSV-2 seropositivity (determined by ELISA during screening)
- no use of chronic anti-HSV therapy for the past 6 months, and not anticipated to require chronic anti-HSV therapy during the study
- sustained plasma HIV RNA<50 copies/mL on HAART for at least 12 months
- no active opportunistic infection for at least 12 months
Who cannot join
- hepatitis C co-infection
- hepatitis B co-infection
- pregnancy or actively planning to become pregnant
- receiving chemotherapy, chronic steroid therapy or other immunomodulatory medications (e.g. interferon, azathioprine, methotrexate, TNF-alpha antagonists, etc.)
- Estimated creatinine clearance <30 mL/min
- Other medical condition likely to cause death within 24 months
- Enrolled in any other interventional clinical trial
Trial locations and contacts
1 site in 1 country.
Canada1 site
Toronto General Hospital, University Health Network
Toronto, Ontario, M5G 2N2
About this study
Official title: VALacyclovir for Inflammation AttenuatioN Trial Pilot (VALIANT Pilot)
The purpose of this study is to compare the levels of immune and inflammatory markers among HIV-1, HSV-2 co-infected adults achieving plasma HIV RNA suppression to <50 copies/mL, between those randomized to valacyclovir and placebo, over a twelve-week intervention period.
Read the detailed description
Highly active antiretroviral therapy (HAART) has dramatically reduced HIV-1 infection (herein referred to as 'HIV') related morbidity and mortality, transforming an invariably fatal disease into a manageable, chronic condition. Yet even HAART-treated HIV infection is characterized by chronic systemic inflammation and immune activation. This systemic inflammatory response is composed of multiple components, and can be quantified by measuring markers of immune activation, inflammatory cytokines, acute phase reactants, endothelial activation markers, and markers of microbial translocation. This inflammation is clinically relevant, as it may contribute directly to HIV disease progression and non-AIDS related morbidity and mortality in HIV-infected patients. Because this inflammation persists even in the context of suppressive HAART, albeit at modestly decreased levels, adjunctive therapeutic strategies to attenuate this persistent inflammatory response are therefore needed. Herpes simplex virus type 2 is a common, clinically important co-infection seen in individuals living with HIV infection, and may contribute to this ongoing inflammation. This pilot trial will investigate whether short-term valacyclovir for HSV-2 suppression can decrease systemic inflammation in HAART-treated, HIV-1, HSV-2 co-infected individuals.
- Conditions
- Human Immunodeficiency Virus, Herpes Simplex
- Being tested
- Valacyclovir, Placebo
- Medical subject headings
- Acquired Immunodeficiency Syndrome, Herpes Simplex
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ValacyclovirDrug
Also called Apo-Valacycyclovir, Valtrex
Valacyclovir will be used at two different dosages (1g po BID and 500mg po BID) to be used for 12 weeks. Supplied as 500mg caplets.
PlaceboDrug
Placebo, supplied as caplets identical in appearance, odour and taste to valacyclovir 500mg caplets.
| Study group | Role | What they receive |
|---|---|---|
| High dose valacyclovir | Experimental | Valacyclovir 1g po BID Receives: Drug: Valacyclovir |
| Low dose valacyclovir | Active comparator | Valacyclovir 500mg po BID Receives: Drug: Valacyclovir |
| Placebo | Placebo comparator | Inert placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage activated CD8+ T-cells
Percentage of CD8+ T-cells co-expressing CD38 and HLA-DR
Measured: 12 weeks
Secondary outcomes (6)
Inflammatory markers
IL-6, hsCRP, sICAM-1, LPS
Measured: 12 weeks
CD4 cell count
CD4 cell count (absolute and percentage)
Measured: 12 weeks
Virologic blips
Plasma HIV RNA level >50 copies/mL but <1000 copies/mL, followed by a repeat plasma HIV RNA level <50 copies/mL.
Measured: 12 weeks
Drug-related adverse events
Adverse events (AEs) are defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the study medication. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not it is related to the medication.
Measured: 18 weeks
HSV reactivations
Clinical reactivations of herpes simplex virus. Simultaneous reactivations at more than one anatomic site will be counted as a single reactivation event.
Measured: 12 weeks
Acyclovir-resistant HSV
Clinical reactivations of herpes simplex virus that are microbiologically confirmed to be caused by acyclovir-resistant virus.
Measured: 18 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2010 (estimated)
- Study startSep 2010
- Primary completionAug 2013
- Study completionAug 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Human Immunodeficiency VirusStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- University of Toronto, Canadian Institutes of Health Research (CIHR)
- Responsible party
- Sponsor
- Investigators
- Darrell HS Tan, MD FRCPC, Principal investigator, University Health Network, University of TorontoSharon L Walmsley, MD FRCPC MSc, Principal investigator, University Health Network, University of Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01176409
- Sponsor's protocol ID
- VALIANT-001
- Acronym
- VALIANT Pilot
- Status last verified
- May 2016
- First submitted
- 4 Aug 2010
- Last updated
- 12 May 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Yi TJ, Walmsley S, Szadkowski L, Raboud J, Rajwans N, Shannon B, Kumar S, Kain KC, Kaul R, Tan DH. A randomized controlled pilot trial of valacyclovir for attenuating inflammation and immune activation in HIV/herpes simplex virus 2-coinfected adults on suppressive antiretroviral therapy. Clin Infect Dis. 2013 Nov;57(9):1331-8. doi: 10.1093/cid/cit539. Epub 2013 Aug 14.
PubMed 23946220
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- VALacyclovir for Inflammation AttenuatioN Trial Pilot (VALIANT Pilot)
- ClinicalTrials.gov ID
- NCT01176409
- Acronym / sponsor ID
- VALIANT Pilot / VALIANT-001
- Conditions
- Human Immunodeficiency Virus, Herpes Simplex
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- University of Toronto, Canadian Institutes of Health Research (CIHR)
- Study start
- Sep 2010
- Primary completion
- Aug 2013 (actual)
- Study completion
- Aug 2013 (actual)
- First posted
- 6 Aug 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to compare the levels of immune and inflammatory markers among HIV-1, HSV-2 co-infected adults achieving plasma HIV RNA suppression to <50 copies/mL, between those randomized to valacyclovir and placebo, over a twelve-week intervention period.
Detailed description
Highly active antiretroviral therapy (HAART) has dramatically reduced HIV-1 infection (herein referred to as 'HIV') related morbidity and mortality, transforming an invariably fatal disease into a manageable, chronic condition. Yet even HAART-treated HIV infection is characterized by chronic systemic inflammation and immune activation. This systemic inflammatory response is composed of multiple components, and can be quantified by measuring markers of immune activation, inflammatory cytokines, acute phase reactants, endothelial activation markers, and markers of microbial translocation. This inflammation is clinically relevant, as it may contribute directly to HIV disease progression and non-AIDS related morbidity and mortality in HIV-infected patients. Because this inflammation persists even in the context of suppressive HAART, albeit at modestly decreased levels, adjunctive therapeutic strategies to attenuate this persistent inflammatory response are therefore needed. Herpes simplex virus type 2 is a common, clinically important co-infection seen in individuals living with HIV infection, and may contribute to this ongoing inflammation. This pilot trial will investigate whether short-term valacyclovir for HSV-2 suppression can decrease systemic inflammation in HAART-treated, HIV-1, HSV-2 co-infected individuals.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| High dose valacyclovir | Experimental | Drug: ValacyclovirValacyclovir 1g po BID |
| Low dose valacyclovir | Active comparator | Drug: ValacyclovirValacyclovir 500mg po BID |
| Placebo | Placebo comparator | Drug: PlaceboInert placebo |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- adult (aged 18 years or older)
- documented HIV-1 infection (determined by EIA and Western blot)
- documented HSV-2 seropositivity (determined by ELISA during screening)
- no use of chronic anti-HSV therapy for the past 6 months, and not anticipated to require chronic anti-HSV therapy during the study
- sustained plasma HIV RNA<50 copies/mL on HAART for at least 12 months
Key exclusion criteria (7 listed)
- hepatitis C co-infection
- hepatitis B co-infection
- pregnancy or actively planning to become pregnant
- receiving chemotherapy, chronic steroid therapy or other immunomodulatory medications (e.g. interferon, azathioprine, methotrexate, TNF-alpha antagonists, etc.)
- Estimated creatinine clearance <30 mL/min
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 |
|---|---|---|
| ValacyclovirAlso: Apo-Valacycyclovir, ValtrexValacyclovir will be used at two different dosages (1g po BID and 500mg po BID) to be used for 12 weeks. Supplied as 500mg caplets. | Drug | High dose valacyclovir, Low dose valacyclovir |
| PlaceboPlacebo, supplied as caplets identical in appearance, odour and taste to valacyclovir 500mg caplets. | Drug | Placebo |
Primary outcome
Percentage activated CD8+ T-cells
Time frame: 12 weeks
Percentage of CD8+ T-cells co-expressing CD38 and HLA-DR
6 secondary outcomes
Inflammatory markers
Time frame: 12 weeks
CD4 cell count
Time frame: 12 weeks
Virologic blips
Time frame: 12 weeks
Drug-related adverse events
Time frame: 18 weeks
HSV reactivations
Time frame: 12 weeks
Acyclovir-resistant HSV
Time frame: 18 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2016.
- Results publication: PubMed 23946220Yi TJ, Walmsley S, Szadkowski L, Raboud J, Rajwans N, Shannon B, Kumar S, Kain KC, Kaul R, Tan DH. A randomized controlled pilot trial of valacyclovir for attenuating inflammation and immune activation in HIV/herpes simplex virus 2-coinfected adults on suppressive antiretroviral therapy. Clin Infect Dis. 2013 Nov;57(9):1331-8. doi: 10.1093/cid/cit539. Epub 2013 Aug 14.
- Study ResultsLink provided by the sponsor.
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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.
Darrell HS Tan, MD FRCPC principal investigator
University Health Network, University of Toronto
Sharon L Walmsley, MD FRCPC MSc principal investigator
University Health Network, University of Toronto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Valacyclovir in people with Human Immunodeficiency Virus and Herpes Simplex, run by University Health Network, Toronto at 1 site in Canada.
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 7 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: finished, as of the sponsor's last update on 12 May 2016. 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 Canada. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Percentage activated CD8+ T-cells (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01176409, which also lists 1 linked publication.
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 12 May 2016.