Downmodulating Monocyte Activation for HIV-1 Associated Neurocognitive Disorders (HAND)

NCT ID: NCT01600170

Last Updated: 2020-11-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-01-31
• Study Completion Date: 2017-10-31

Brief 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. 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

1) 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

Keywords

HIV; monocytes; CD16+; statins; mcp1; inflammation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Atorvastatin

Participants were given atorvastatin for 12 weeks at various doses based on their specific HAART treatment.

Group Type: ACTIVE_COMPARATOR

Atorvastatin (generic Lipitor)

Intervention Type: 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.

Placebo

Participants were given Placebo tablets for 12 weeks.

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

A substance containing no medication and prescribed or given to reinforce a patient's expectation to get well.

Interventions

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.

Intervention Type: DRUG

placebo

A substance containing no medication and prescribed or given to reinforce a patient's expectation to get well.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. 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.

2. HIV viral load less than 200 copies/ml for more than 6 months at time of screening.

3. Nadir CD4 count less than 350 and current CD4 counts greater than 100 cells/ul.

4. Hs-CRP levels above 2mg/L.

5. Willingness to use a method of contraception during the study period.

6. Willingness to comply with study evaluations for LP sub-study.

7. Karnofsky performance score of 80 or higher.

8. If female, willing to undergo pregnancy testing on a monthly basis and not breastfeeding.

9. Hemoglobin greater than or equal to 9.0 g/dL for female and 10.0 g/dL for male subjects.

10. men and women 18 years or older.

Exclusion Criteria

1. Concomitant use of fibric acid derivatives or other lipid lowering agents including patients on statins and Ezetimibe.

2. Use of any anti-inflammatory drugs (OTC or prescription) on a daily basis.

3. Pregnancy or breastfeeding

4. Active drug use or alcohol abuse/dependence which in the opinion of researchers will interfere with the patients' ability to participate in the study.

5. Allergy or hypersensitivity to Atorvastatin or any of its components.

6. History of myositis or rhabdomyolysis with use of any statins.

7. 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.

8. History of inflammatory muscle disease such a poly or dermatomyositis.

9. Serious intercurrent illness requiring systemic treatment and/or hospitalization within 30 days of entry.

10. Evidence of active opportunistic infections requiring treatment or neoplasms that require chemotherapy during study period.

11. CPK greater than 3 times the ULN.

12. Known active liver disease or AST/ALT greater than 3 times the ULN.

13. Renal insufficiency, indicated by serum creatinine greater than 2mg/dL.

14. 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.

15. Documented HCV infection.

16. NYHA class III or IV congestive heart failure.

17. Active IV drug use within 1 year prior to entry.

18. For LP sub-study, allergy to Lidocaine.

19. Coronary artery disease or equivalent including Diabetes mellitus.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ronald G Collman, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

University of Pennsylvania School of Medicine

Philadelphia, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

IRB Protocol # 815512

Identifier Type: -

Identifier Source: org_study_id