HIV InfectionsNCT00672932

Raltegravir Augmentation on Persistent Central Nervous System (CNS) Immunoactivation in Treated HIV-1 Patients

A study testing raltegravir in people with HIV Infections, run by University of California, San Francisco at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: HIV Infections
What is being tested?: raltegravir
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 18 participants
Where: 1 siteUnited States
Study dates: Apr 2008to Feb 2011
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 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Capacity to provide informed consent.
Documented HIV-1 infection.
History of continuous cART treatment (with at least three drugs) for at least 2 years.
Documentation of 'undetectable' plasma HIV-1 RNA for at least 1 year.
HIV-1 RNA <50 copies/mL in plasma and CSF at screening visit.

Who cannot join

Contraindication to LP (suspicion of CNS mass lesion, bleeding diathesis, etc.).
Prior experience with raltegravir or contraindication to raltegravir treatment, including medication interactions that might compromise ongoing antiretroviral therapy or treatment of other conditions.
Active opportunistic infections or neurological diseases.
Other conditions or treatments likely to interfere with treatment or evaluation.
Hemoglobin < 10 Gm/dL.
Pregnant or anticipating pregnancy during study.
Active substance abuse.
Subjects taking rifampin, phenytoin, Phenobarbital or other drugs that accelerate raltegravir metabolism and might decrease its tissue concentrations.

Trial locations and contacts

1 site in 1 country.

United States1 site

Ucsf Ccrc, Sfgh
San Francisco, California, 94110

Other trials in United States

About this study

Official title: Pilot Study of Raltegravir Augmentation on Persistent Central Nervous System (CNS) Immunoactivation in Treated HIV-1 Patients

This pilot study focuses on the persistence of central nervous system (CNS) immune activation that has been observed in the presence of 'effective' combination antiretroviral therapy (cART). Attention to this issue is based on the fear that chronic CNS immunoactivation can cause indolent brain injury that will eventually compromise brain function as patients survive for years on treatment. A leading hypothesis explaining this continued immunoactivation is that viral replication continues within the brain at a level too low for detection in cerebrospinal fluid (CSF), yet sufficient to stimulate local immunoactivation. Based on this hypothesis, we propose to use augmented treatment with raltegravir to test whether additional suppression of this hypothesized CNS HIV-1 replication will reduce continued CNS immunoactivation.

Conditions: HIV Infections
Being tested: raltegravir
Keywords: raltegravir, central nervous system (CNS), HIV-1, AIDS, cerebrospinal fluid (CSF), immunoactivation, antiretroviral therapy, suppression
Medical subject headings: HIV Infections, Acquired Immunodeficiency Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

raltegravirDrug
Also called Isentress
400 mg two times daily for three months

Study groups in NCT00672932
Study group	Role	What they receive
raltegravir group	Experimental	The raltegravir dosing will be 400mg twice daily by mouth. Subjects will continue all of their regular medications throughout the protocol. Receives: Drug: raltegravir
No augmented treatment	No intervention	Subjects randomized not to receive augmented treatment will continue in the study with their regular antiretroviral regimen.

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in CSF Concentrations of Neopterin After 12 Weeks
CSF markers of immuno¬activation and inflammation after 12 weeks compared to baseline.
Measured: three months (Rollover subjects were assessed for a second baseline after the initial 12 week period)

Secondary outcomes (1)

Change From Baseline in CD8+ T Cell Co-expression of CD38 and HLA-DR
Blood CD8+ T cell activation as indicated by percentage of cells in fresh specimens coexpressing surface CD38 and human leukocyte antigen (HLA)-DR.
Measured: three months (Rollover subjects were assessed for a second baseline after the initial 12 week period)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 2008Feb 2011

First posted6 May 2008 (estimated)
Study startApr 2008
Primary completionOct 2010
Study completionFeb 2011

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.
Publications (1)Papers the sponsor has linked to this study.
Other trials for HIV InfectionsStudies of the same condition, open and under way.
More trials run by University of California, San FranciscoThe 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
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 18 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00672932
Sponsor's protocol ID: CCRC5004
Other IDs: R01MH062701
Status last verified: May 2013
First submitted: 29 Apr 2008
Last updated: 5 Jul 2013
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Dahl V, Lee E, Peterson J, Spudich SS, Leppla I, Sinclair E, Fuchs D, Palmer S, Price RW. Raltegravir treatment intensification does not alter cerebrospinal fluid HIV-1 infection or immunoactivation in subjects on suppressive therapy. J Infect Dis. 2011 Dec 15;204(12):1936-45. doi: 10.1093/infdis/jir667. Epub 2011 Oct 21.
PubMed 22021620

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 5 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Pilot Study of Raltegravir Augmentation on Persistent Central Nervous System (CNS) Immunoactivation in Treated HIV-1 Patients
ClinicalTrials.gov ID: NCT00672932
Acronym / sponsor ID: CCRC5004
Conditions: HIV Infections
Keywords: raltegravir, central nervous system (CNS), HIV-1, AIDS, cerebrospinal fluid (CSF), immunoactivation, antiretroviral therapy, suppression
Study type: Interventional
Recruitment status: Completed
Enrolment: 18 participants (actual)
Lead sponsor: University of California, San FranciscoUniversity, hospital or other
Collaborators: National Institute of Mental Health (NIMH), Merck Sharp & Dohme LLC
Study start: Apr 2008
Primary completion: Oct 2010 (actual)
Study completion: Feb 2011 (actual)
First posted: 6 May 2008 (estimated)
Results: Posted 5 Jul 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
raltegravir group	Experimental	Drug: raltegravirThe raltegravir dosing will be 400mg twice daily by mouth. Subjects will continue all of their regular medications throughout the protocol.
No augmented treatment	No intervention	–Subjects randomized not to receive augmented treatment will continue in the study with their regular antiretroviral regimen.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Capacity to provide informed consent.
Documented HIV-1 infection.
History of continuous cART treatment (with at least three drugs) for at least 2 years.
Documentation of 'undetectable' plasma HIV-1 RNA for at least 1 year.
HIV-1 RNA <50 copies/mL in plasma and CSF at screening visit.

Key exclusion criteria (8 listed)

Contraindication to LP (suspicion of CNS mass lesion, bleeding diathesis, etc.).
Prior experience with raltegravir or contraindication to raltegravir treatment, including medication interactions that might compromise ongoing antiretroviral therapy or treatment of other conditions.
Active opportunistic infections or neurological diseases.
Other conditions or treatments likely to interfere with treatment or evaluation.
Hemoglobin < 10 Gm/dL.

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
raltegravirAlso: Isentress400 mg two times daily for three months	Drug	raltegravir group

Primary outcome

Change in CSF Concentrations of Neopterin After 12 Weeks
Time frame: three months (Rollover subjects were assessed for a second baseline after the initial 12 week period)
CSF markers of immuno¬activation and inflammation after 12 weeks compared to baseline.

1 secondary outcome

Change From Baseline in CD8+ T Cell Co-expression of CD38 and HLA-DR
Time frame: three months (Rollover subjects were assessed for a second baseline after the initial 12 week period)

Results and safety

Results posted to the registry on 5 Jul 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Raltegravir Group	9	9
No Augmented Treatment Then Optional Rollover	9	9

Primary outcome: Change in CSF Concentrations of Neopterin After 12 Weeks

Time frame: three months (Rollover subjects were assessed for a second baseline after the initial 12 week period). Mean (Standard Deviation). Unit: nmol/L

Measure	Raltegravir Group n = 14	No Augmented Treatment n = 9
Value	0.1 (0.3)	0.3 (1.1)

Population analysed: One subject in the raltegravir group was censored when a pharmacological study showed no drug in either plasma (n=9) or CSF. Six subjects randomized to no drug later rolled over to receive raltegravir. Primary analysis treated the rollover subjects as independent and compared 14 intensified to 9 nonintensified subject experiences.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: 12 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Raltegravir Group	0 of 15 (0%)	0 of 15 (0%)	Not reported
No Augmented Treatment	0 of 9 (0%)	0 of 9 (0%)	Not reported

Limitations and caveats (from the sponsor): The underlying hypothesis might not have actually been addressed because of the particular makeup of the subject group with minimal CNS infection and immunoactivation that left little room to discern a therapeutic effect.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2013.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 22021620Dahl V, Lee E, Peterson J, Spudich SS, Leppla I, Sinclair E, Fuchs D, Palmer S, Price RW. Raltegravir treatment intensification does not alter cerebrospinal fluid HIV-1 infection or immunoactivation in subjects on suppressive therapy. J Infect Dis. 2011 Dec 15;204(12):1936-45. doi: 10.1093/infdis/jir667. Epub 2011 Oct 21.

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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.

Richard Price, MD principal investigator

University of California, San Francisco

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing raltegravir in people with HIV Infections, run by University of California, San Francisco 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 5 inclusion and 8 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 5 Jul 2013. 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. 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 Jul 2013). 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 in CSF Concentrations of Neopterin After 12 Weeks (time frame: three months (Rollover subjects were assessed for a second baseline after the initial 12 week period)). 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 NCT00672932, 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 5 Jul 2013.