HIV DementiaPhase 4NCT01600170
Downmodulating Monocyte Activation for HIV-1 Associated Neurocognitive Disorders (HAND)
A Phase 4 study testing Atorvastatin (generic Lipitor) in people with HIV Dementia, run by University of Pennsylvania at 1 site in United States.
Trial summary
HIV associated neurological disorders (HAND), are a major problem even in ART treated people. HAND results from chronic inflammation which is largely attributed to expansion and activation of monocytes. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- HIV Dementia
- What is being tested?
- Atorvastatin (generic Lipitor)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2013to Oct 2017
- Phase
- Phase 4
- 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 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Chronic HIV-1 infected individuals on HAART (with no change in treatment within 4 weeks of study entry) and willing to continue therapy for the duration of the study.
- HIV viral load less than 200 copies/ml for more than 6 months at time of screening.
- Nadir CD4 count less than 350 and current CD4 counts greater than 100 cells/ul.
- Hs-CRP levels above 2mg/L.
- Willingness to use a method of contraception during the study period.
- Willingness to comply with study evaluations for LP sub-study.
Show all 10Show fewer
- Karnofsky performance score of 80 or higher.
- If female, willing to undergo pregnancy testing on a monthly basis and not breastfeeding.
- Hemoglobin greater than or equal to 9.0 g/dL for female and 10.0 g/dL for male subjects.
- men and women 18 years or older.
Who cannot join
- Concomitant use of fibric acid derivatives or other lipid lowering agents including patients on statins and Ezetimibe.
- Use of any anti-inflammatory drugs (OTC or prescription) on a daily basis.
- Pregnancy or breastfeeding
- Active drug use or alcohol abuse/dependence which in the opinion of researchers will interfere with the patients' ability to participate in the study.
- Allergy or hypersensitivity to Atorvastatin or any of its components.
- History of myositis or rhabdomyolysis with use of any statins.
Show all 19Show fewer
- Patients who are on concurrent immunomodulatory agents, including systemic corticosteroids (nasal or inhaled) will be ineligible for 3 months after completion of therapy with the agent.
- History of inflammatory muscle disease such a poly or dermatomyositis.
- Serious intercurrent illness requiring systemic treatment and/or hospitalization within 30 days of entry.
- Evidence of active opportunistic infections requiring treatment or neoplasms that require chemotherapy during study period.
- CPK greater than 3 times the ULN.
- Known active liver disease or AST/ALT greater than 3 times the ULN.
- Renal insufficiency, indicated by serum creatinine greater than 2mg/dL.
- Absolute neutrophil counts less than 1000/ul; hemoglobin less than 10g/dL for males and less than 9g/dL for females; platelet counts less than 100,000/mm3.
- Documented HCV infection.
- NYHA class III or IV congestive heart failure.
- Active IV drug use within 1 year prior to entry.
- For LP sub-study, allergy to Lidocaine.
- Coronary artery disease or equivalent including Diabetes mellitus.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania School of Medicine
Philadelphia, Pennsylvania, 19104
About this study
Official title: Statin Modulation of Monocyte/Macrophage Activation for HAND Treatment
HIV associated neurological disorders (HAND), are a major problem even in ART treated people. HAND results from chronic inflammation which is largely attributed to expansion and activation of monocytes. These activated monocytes, some of which also carry virus to the brain, invade the CNS and release cytokines / chemokines resulting in further recruitment of monocytes, as well as release viral proteins which injure neurons and cause activation of other brain cells. Persistent monocyte/macrophage activation is thus a potential critical target for adjunctive therapy to treat or prevent HAND. The investigators therefore propose to study the effects of a statin drug (Atorvastatin), which has anti-inflammatory functions, on the monocyte activation status in ART treated HIV+ individuals.
The investigators objectives are based on the hypothesis that Atorvastatin treatment will reduce the inflammatory and activated phenotype and function of monocytes which have been linked to HIV associated neuropathogenesis and occur in HIV infected subjects despite ART. In this study the investigators propose to
- define the effect of Atorvastatin on monocyte activation in HIV infected / ART treated subjects in a double blind, placebo controlled crossover study
- Conditions
- HIV Dementia
- Being tested
- Atorvastatin (generic Lipitor), placebo
- Keywords
- HIV, monocytes, CD16+, statins, mcp1, inflammation
- Medical subject headings
- AIDS Dementia Complex, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Atorvastatin (generic Lipitor)Drug
Atorvastatin is an FDA approved prescription drug which is frequently used to lower cholesterol levels.It is available in the form of tablets ranging in dose from 10-80mg.
placeboDrug
A substance containing no medication and prescribed or given to reinforce a patient's expectation to get well.
| Study group | Role | What they receive |
|---|---|---|
| Atorvastatin | Active comparator | Participants were given atorvastatin for 12 weeks at various doses based on their specific HAART treatment. Receives: Drug: Atorvastatin (generic Lipitor) |
| Placebo | Placebo comparator | Participants were given Placebo tablets for 12 weeks. Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Week 0 in Percentage of Blood Monocytes Expressing Surface Marker CD16 at 12 Weeks, as a Result of Treatment.
Whole blood drawn from participants were stained with fluorochrome tagged antibodies to the surface markers. Stained whole blood cells were then acquired on a flow cytometer and analyzed using the Flowjo software to determine the change in percentage of monocytes expressing the specific marker (CD16) at 12 wk versus 0wk within each Period.
Data is shown as fold change over 12 weeks, in percent positive monocytes expressing surface markers.
Change in primary outcome measures in each treatment arm is expressed as fold change (at week 12 versus week 0). For eg. outcome measure CD14+CD16+ in atorvastatin arm shows a mean value of 1.14. This means at 12 weeks there is an increase of 0.14 fold in the percent monocyte population expressing CD14+CD16+ marker, versus 0 week. Similarly in the placebo group. If fold change in atorvastatin group is smaller than in placebo group, then the treatment had no effect.
Measured: Week 0 and week 12
Change From Baseline Within Each Period in Levels of Plasma Inflammatory Marker MCP-1 in Chronic HIV+/ HAART+ Subjects Over 12 Weeks.
Monocyte specific inflammatory soluble factor MCP-1 was measured by Luminex in plasma of HIV+/HAART+ subjects at baseline and at 12 weeks following treatment (atorvastatin or placebo).
Data is shown as fold change in concentration of MCP-1 over 12wks within each treatment period.
Measured: Week 0 and week 12
Change From Week 0 in Percentage of Blood Monocytes Expressing Surface Marker CD163 at 12 Weeks, as a Result of Treatment.
Whole blood drawn from participants were stained with fluorochrome tagged antibodies to the surface marker CD163. Stained whole blood cells were then acquired on a flow cytometer and analyzed using the Flowjo software to determine the change in percentage of monocytes expressing the specific marker (CD163) at 12 wk versus 0wk within each Period.
Data in each treatment arm is shown as 'mean difference' at 12 weeks versus 0 week, in percent positive monocytes expressing surface marker CD163.
Data is expressed as the difference of the mean values at week 12 and week 0. The negative values mean that the mean values at 12 week were lower than the mean values at 0 week.
Measured: week 0 and week 12
Change From Week 0 in Percentage of Blood Monocytes Expressing Surface Marker CCR2 at 12 Weeks, as a Result of Treatment.
Whole blood drawn from participants were stained with fluorochrome tagged antibodies to the surface marker CCR2. Stained whole blood cells were then acquired on a flow cytometer and analyzed using the Flowjo software to determine the change in percentage of monocytes expressing the specific marker (CCR2) at 12 wk versus 0wk within each Period.
Data in each treatment arm is shown as fold change over 12 weeks, in percent positive monocytes expressing surface marker CCR2.
Measured: week 0 and week 12
Change From Baseline Within Each Period in Levels of Plasma Inflammatory Marker sCD14 in Chronic HIV+/ HAART+ Subjects Over 12 Weeks.
Monocyte specific inflammatory soluble factor sCD14 was measured by ELISA in plasma of HIV+/HAART+ subjects at baseline and at 12 weeks following treatment (atorvastatin or placebo).
Data is shown as fold change in concentration of sCD14 over 12wks within each treatment period.
Measured: 0 week and 12 week
Secondary outcomes (4)
Change From Week 0 to Week 12 in Percentage of Blood Monocytes Expressing Surface Marker Tissue Factor (TF), Following Treatment.
Whole blood drawn from participants were stained with fluorochrome tagged antibodies to the surface marker TF. Stained whole blood cells were then acquired on a flow cytometer and analyzed using the Flowjo software to determine the change in percentage of monocytes expressing the specific marker TF at 12 wk versus 0wk within each Period.
Data are expressed as fold change.
Measured: 0 week and 12 week
Change From 0 Week in Levels of Plasma Inflammatory Marker hsCRP in Chronic HIV+/ HAART+ Subjects Over 12 Weeks, Following Treatment.
Monocyte specific inflammatory soluble factor hsCRP was measured by Quest in plasma of HIV+/HAART+ subjects at baseline and at 12 weeks following treatment (atorvastatin or placebo).
Data shown as fold change at week 12 versus week 0.
Measured: 0 week and 12 week
Change From Week 0 to Week 12 in Percentage of Blood Monocytes Expressing Surface Marker CD38, Following Treatment.
Whole blood drawn from participants were stained with fluorochrome tagged antibodies to the surface marker CD38. Stained whole blood cells were then acquired on a flow cytometer and analyzed using the Flowjo software to determine the change in percentage of monocytes expressing the specific marker CD38 at 12 wk versus 0wk within each Period.
Data are expressed as fold change at 12 week versus week 0.
Measured: 0 week and 12 week
Change From Week 0 in Plasma sCD163 Levels, at Week 12 Following Treatment.
Monocyte specific inflammatory soluble factor sCD163 was measured by ELISA in plasma of HIV+/HAART+ subjects at baseline and at 12 weeks following treatment (atorvastatin or placebo).
Data are expressed as fold change at 12 week versus week 0.
Measured: 0 week and 12 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2012 (estimated)
- Study startJan 2013
- Primary completionOct 2017
- Study completionOct 2017
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 HIV DementiaStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ronald G Collman, MD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01600170
- Sponsor's protocol ID
- IRB Protocol # 815512
- Status last verified
- Oct 2020
- First submitted
- 14 May 2012
- Last updated
- 23 Nov 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Statin Modulation of Monocyte/Macrophage Activation for HAND Treatment
- ClinicalTrials.gov ID
- NCT01600170
- Acronym / sponsor ID
- IRB Protocol # 815512
- Conditions
- HIV Dementia
- Keywords
- HIV, monocytes, CD16+, statins, mcp1, inflammation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- Jan 2013
- Primary completion
- Oct 2017 (actual)
- Study completion
- Oct 2017 (actual)
- First posted
- 16 May 2012 (estimated)
- Results
- Posted 23 Nov 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
HIV associated neurological disorders (HAND), are a major problem even in ART treated people. HAND results from chronic inflammation which is largely attributed to expansion and activation of monocytes. These activated monocytes, some of which also carry virus to the brain, invade the CNS and release cytokines / chemokines resulting in further recruitment of monocytes, as well as release viral proteins which injure neurons and cause activation of other brain cells. Persistent monocyte/macrophage activation is thus a potential critical target for adjunctive therapy to treat or prevent HAND. The investigators therefore propose to study the effects of a statin drug (Atorvastatin), which has anti-inflammatory functions, on the monocyte activation status in ART treated HIV+ individuals.
The investigators objectives are based on the hypothesis that Atorvastatin treatment will reduce the inflammatory and activated phenotype and function of monocytes which have been linked to HIV associated neuropathogenesis and occur in HIV infected subjects despite ART. In this study the investigators propose to
- define the effect of Atorvastatin on monocyte activation in HIV infected / ART treated subjects in a double blind, placebo controlled crossover study
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Atorvastatin | Active comparator | Drug: Atorvastatin (generic Lipitor)Participants were given atorvastatin for 12 weeks at various doses based on their specific HAART treatment. |
| Placebo | Placebo comparator | Drug: placeboParticipants were given Placebo tablets for 12 weeks. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- Chronic HIV-1 infected individuals on HAART (with no change in treatment within 4 weeks of study entry) and willing to continue therapy for the duration of the study.
- HIV viral load less than 200 copies/ml for more than 6 months at time of screening.
- Nadir CD4 count less than 350 and current CD4 counts greater than 100 cells/ul.
- Hs-CRP levels above 2mg/L.
- Willingness to use a method of contraception during the study period.
Key exclusion criteria (19 listed)
- Concomitant use of fibric acid derivatives or other lipid lowering agents including patients on statins and Ezetimibe.
- Use of any anti-inflammatory drugs (OTC or prescription) on a daily basis.
- Pregnancy or breastfeeding
- Active drug use or alcohol abuse/dependence which in the opinion of researchers will interfere with the patients' ability to participate in the study.
- Allergy or hypersensitivity to Atorvastatin or any of its components.
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 |
|---|---|---|
| Atorvastatin (generic Lipitor)Atorvastatin is an FDA approved prescription drug which is frequently used to lower cholesterol levels.It is available in the form of tablets ranging in dose from 10-80mg. | Drug | Atorvastatin |
| placeboA substance containing no medication and prescribed or given to reinforce a patient's expectation to get well. | Drug | Placebo |
Primary outcome
Change From Week 0 in Percentage of Blood Monocytes Expressing Surface Marker CD16 at 12 Weeks, as a Result of Treatment.
Time frame: Week 0 and week 12
Whole blood drawn from participants were stained with fluorochrome tagged antibodies to the surface markers. Stained whole blood cells were then acquired on a flow cytometer and analyzed using the Flowjo software to determine the change in percentage of monocytes expressing the specific marker (CD16) at 12 wk versus 0wk within each Period. Data is shown as fold change over 12 weeks, in percent positive monocytes expressing surface markers. Change in primary outcome measures in each treatment arm is expressed as fold change (at week 12 versus week 0). For eg. outcome measure CD14+CD16+ in atorvastatin arm shows a mean value of 1.14. This means at 12 weeks there is an increase of 0.14 fold in the percent monocyte population expressing CD14+CD16+ marker, versus 0 week. Similarly in the placebo group. If fold change in atorvastatin group is smaller than in placebo group, then the treatment had no effect.
Change From Baseline Within Each Period in Levels of Plasma Inflammatory Marker MCP-1 in Chronic HIV+/ HAART+ Subjects Over 12 Weeks.
Time frame: Week 0 and week 12
Monocyte specific inflammatory soluble factor MCP-1 was measured by Luminex in plasma of HIV+/HAART+ subjects at baseline and at 12 weeks following treatment (atorvastatin or placebo). Data is shown as fold change in concentration of MCP-1 over 12wks within each treatment period.
Change From Week 0 in Percentage of Blood Monocytes Expressing Surface Marker CD163 at 12 Weeks, as a Result of Treatment.
Time frame: week 0 and week 12
Whole blood drawn from participants were stained with fluorochrome tagged antibodies to the surface marker CD163. Stained whole blood cells were then acquired on a flow cytometer and analyzed using the Flowjo software to determine the change in percentage of monocytes expressing the specific marker (CD163) at 12 wk versus 0wk within each Period. Data in each treatment arm is shown as 'mean difference' at 12 weeks versus 0 week, in percent positive monocytes expressing surface marker CD163. Data is expressed as the difference of the mean values at week 12 and week 0. The negative values mean that the mean values at 12 week were lower than the mean values at 0 week.
Change From Week 0 in Percentage of Blood Monocytes Expressing Surface Marker CCR2 at 12 Weeks, as a Result of Treatment.
Time frame: week 0 and week 12
Whole blood drawn from participants were stained with fluorochrome tagged antibodies to the surface marker CCR2. Stained whole blood cells were then acquired on a flow cytometer and analyzed using the Flowjo software to determine the change in percentage of monocytes expressing the specific marker (CCR2) at 12 wk versus 0wk within each Period. Data in each treatment arm is shown as fold change over 12 weeks, in percent positive monocytes expressing surface marker CCR2.
Change From Baseline Within Each Period in Levels of Plasma Inflammatory Marker sCD14 in Chronic HIV+/ HAART+ Subjects Over 12 Weeks.
Time frame: 0 week and 12 week
Monocyte specific inflammatory soluble factor sCD14 was measured by ELISA in plasma of HIV+/HAART+ subjects at baseline and at 12 weeks following treatment (atorvastatin or placebo). Data is shown as fold change in concentration of sCD14 over 12wks within each treatment period.
4 secondary outcomes
Change From Week 0 to Week 12 in Percentage of Blood Monocytes Expressing Surface Marker Tissue Factor (TF), Following Treatment.
Time frame: 0 week and 12 week
Change From 0 Week in Levels of Plasma Inflammatory Marker hsCRP in Chronic HIV+/ HAART+ Subjects Over 12 Weeks, Following Treatment.
Time frame: 0 week and 12 week
Change From Week 0 to Week 12 in Percentage of Blood Monocytes Expressing Surface Marker CD38, Following Treatment.
Time frame: 0 week and 12 week
Change From Week 0 in Plasma sCD163 Levels, at Week 12 Following Treatment.
Time frame: 0 week and 12 week
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Nov 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for HIV Dementia
RecruitingPhase 1/2
SV2A & TSPO PET Imaging Measures to Reveal Mechanisms of HIV Neuropathogenesis During Antiretroviral Therapy
HIV Associated Neurocognitive Disorder, HIV Dementia
Not yet recruiting
The Impact of Brief Behavioral Treatment for Insomnia Versus Brief Mindfulness Treatment on Cognition and Sleep Health in Adults (Age 50+) With HIV
Insomnia, Cognition
RecruitingObservational study
ALS Research Collaborative
Amyotrophic Lateral Sclerosis, ALS (Amyotrophic Lateral Sclerosis)
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.
Ronald G Collman, MD principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Atorvastatin (generic Lipitor) in people with HIV Dementia, run by University of Pennsylvania 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 10 inclusion and 19 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 23 Nov 2020. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Nov 2020). 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 Week 0 in Percentage of Blood Monocytes Expressing Surface Marker CD16 at 12 Weeks, as a Result of Treatment. (time frame: Week 0 and week 12). The study lists 5 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 23 Nov 2020.