Effect of HAART Vs. Statin Treatment on Endothelial Function and Inflammation/Coagulation

NCT01515813 | Withdrawn Phase 2 DMC

• 2 other identifiers: ACTG A52921U01AI068636
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 9

Brief Summary

Since people started taking HIV medications, illnesses related to AIDS have decreased, but other serious illnesses like heart disease (heart attacks) and certain kinds of cancer have increased. Studies show that HIV causes changes in the lining of the arteries and also causes inflammation (irritation) inside the body that may play a role in diseases like heart attacks and strokes. The levels of inflammation and artery lining health can also affect how well your brain works. These changes cannot be felt, but can be measured. Artery lining health can be looked at with a test that uses a blood pressure cuff on your arm to see how the artery responds when air is let in and out of the cuff. An ultrasound (machine that uses sound waves) is used to look at the artery during the test. This test is called Flow Mediated Dilation or FMD for short. Inflammation can be checked with blood tests (blood tests that measure this irritation inside the body that you cannot feel). HIV medications can improve the artery lining health and can partially lower levels of inflammation in the blood; however, these levels of inflammation may not be able to return back to normal. Pravastatin sodium is a medication that is approved by the Food and Drug Administration (FDA) for treating high cholesterol. Pravastatin sodium has also been able to improve the health of the lining of the arteries and lower the level of inflammation in people with other diseases, but has not been studied or approved for this purpose in people who have HIV. This research study will look at the effects of two types of medications used separately or together on the health of the lining of arteries and levels of inflammation in the blood: Atripla (a HIV medication) and pravastatin sodium. This study will also look at the effects of Atripla and pravastatin sodium on cholesterol levels, tests that measure how well you can think and calculate (tests of neurocognitive function), and at the effects of Atripla on the levels of pravastatin sodium in the blood.

Conditions

HIV-1 Infection

Outcome Measures

Primary Outcomes (1)

• Change in brachial artery FMD

  From week 0 to week 12

Secondary Outcomes (13)

• Change in IL-6

  From week 0 to week 12

• Change in hs-CRP

  From week 0 to week 12

• Change in D-dimer

  From week 0 to week 12

• Change in non-HDL cholesterol

  From week 0 to week 12

• Change in fasting triglycerides

  From week 0 to week 12

Study Arms (3)

Arm A: Pravastatin sodium alone for 24 weeks

EXPERIMENTAL

One 40 mg tablet of Pravastatin sodium taken orally once daily for 24 weeks starting at week 0 and ending at week 24.

Drug: Pravastatin sodium

Arm B: EFV/FTC/TDF plus Pravastatin sodium at week 13

EXPERIMENTAL

EFV/FTC/TDF once daily for 24 weeks starting at week 0 and ending at week 24 plus pravastatin sodium (80 mg)once daily for 12 weeks starting at week 13 ending at week 24.

Drug: Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate; Drug: Pravastatin sodium

Arm C: Pravastatin sodium + EFV/FTC/TDF for 24 weeks

EXPERIMENTAL

Participants will be administered Pravastatin sodium once daily for 24 weeks starting at week 0 and ending at week 24 plus EFV/FTC/TDF once daily for 24 weeks starting week 0 and ending at week 24.

Drug: Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate; Drug: Pravastatin sodium

Interventions

Pravastatin sodium DRUG

One 40 mg tablet of Pravastatin sodium taken orally once daily.

Arm A: Pravastatin sodium alone for 24 weeks

Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate DRUG

Participant will be administered one tablet of Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate (EFV/FTC/TDF)600 mg/200 mg/300 mg taken orally once daily

Also known as: EFV/FTC/TDF

Arm B: EFV/FTC/TDF plus Pravastatin sodium at week 13; Arm C: Pravastatin sodium + EFV/FTC/TDF for 24 weeks

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV-1 infection
• Willingness to defer initiation of ART for up to 24 weeks or statin therapy for up to 12 weeks after study entry.
• CD4+ cell count \>500/mm3 within 60 days prior to study entry obtained at any laboratory that has a CLIA certification or its equivalent.
• No prior ART of more than 10 cumulative days with the following exceptions:
• Use of ART drugs as part of post-exposure prophylaxis (PEP) provided the participant did not acquire HIV-1 infection from the event that required PEP.
• ART use during pregnancy that resulted in virologic suppression based on the assay available at the time and was not complicated while on therapy either by detectable HIV-1 RNA following suppression or the development of resistance. Women who received ZDV monotherapy prior to the availability of viral load testing will still be considered eligible as long as ZDV was not taken for more than 12 weeks. ART must have been stopped within 4 weeks of delivery and cannot have been received within 6 months of the A5292 screening visit.
• Receipt of ARV drugs while HIV-uninfected, with documentation of negative HIV-1 serology at least 90 days after completion of ARV drugs.
• No lipid-lowering medication (prescription or non-prescription) within 60 days prior to study entry. This includes all statin drugs, omega-3-fatty acids/fish oil (if dose \> 1 g/day), red yeast rice (any dose), and niacin products (e.g., niacin, nicotinic acid, vitamin B3; if dose of \>100 mg/day), in addition to those listed on the A5292 PSWP.
• No ART within the past 30 days.
• Ability and willingness of participant or legal guardian/representative to provide informed consent.
• In the opinion of the investigator, no medical, mental health or other condition that precludes participation.
• Certain laboratory values obtained within 60 days prior to entry, as indicated in section 4.1.10 of the protocol.
• Framingham Risk Score (FRS) greater than/equal to 10% OR FRS greater than/equal to 6% if hsCRP \> 3.0 mg/L OR participant has controlled type ll diabetes mellitus.
• Completion of the pre-entry FMD assessment.
• For women of reproductive potential, negative serum or urine pregnancy test with a sensitivity of ≤ 25 mIU/mL at screening and within 72 hours prior to study entry.

You may not qualify if:

• Pregnancy or breast-feeding.
• Known allergy/sensitivity or any hypersensitivity to components of study drug(s) or their formulation.
• Known and documented cardiovascular disease (history of MI, coronary artery bypass graft surgery, percutaneous coronary intervention, stroke, transient ischemic attack, peripheral arterial disease with ABI \<0.9 or claudication).
• Uncontrolled type II diabetes mellitus.
• History of hepatic cirrhosis.
• Known chronic inflammatory conditions such as, but not limited to, rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis, inflammatory bowel disease (i.e., Crohn's disease or ulcerative colitis), chronic pancreatitis, or autoimmune hepatitis, myositis, or myopathy.
• Known active or recent (not fully resolved within 30 days prior to study entry) systemic bacterial, fungal, parasitic, or viral infections.
• Serious illness or trauma requiring systemic treatment and/or hospitalization within 4 weeks prior to study entry.
• Febrile (temperature \>100.4 F \[38 C\]) or acute illness on the day the initial study FMD is performed.
• Current severe congestive heart failure (New York Heart Association \[NYHA\] Class III or IV). See A5292 MOPS for stages of heart failure.
• Uncontrolled hypertension within 60 days prior to study entry (systolic \> 160 mm Hg or diastolic \> 100 mm Hg) from an average of two or more readings on two or more occasions. NOTE: If the initial blood pressure reading is \>160 mm Hg (systolic) or \> 100 mm Hg (diastolic), then the participant must come back to the clinic for additional readings prior to study entry.
• Documented untreated hypothyroidism per participant's medical records. Subjects with treated hypothyroidism are allowed. NOTE: A thyroid stimulating hormone evaluation is not required by this study.
• Current use of thyroid hormone supplements (e.g., levothyroxine, liothyronine, thyroid extract) other than for treatment of hypothyroidism.
• Active cancer requiring systemic chemotherapy or radiation.
• Active brain infection, brain neoplasm, or space-occupying brain lesion requiring acute, or chronic therapy. Subjects with active fungal meningitis, toxoplasmosis, or CNS lymphoma are excluded from participation.

Sponsors & Collaborators

• Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (9)

UCLA CARE Center CRS (601)

Los Angeles, California, 90095, United States

Location

Harbor-UCLA Med. Ctr. CRS (603)

Torrance, California, 90502, United States

Location

Washington University CRS (2101)

St Louis, Missouri, 63110, United States

Location

Unc Aids Crs (3201)

Chapel Hill, North Carolina, 27514, United States

Location

Duke University Medical Center Adult CRS (1601)

Durham, North Carolina, 27710, United States

Location

Regional Center for Infectious Disease, Wendover Medical Center CRS (3203)

Greensboro, North Carolina, 27401, United States

Location

The Ohio State University AIDS CRS (2301)

Colombus, Ohio, 43210, United States

Location

Vanderbilt Therapeutics CRS (3652)

Nashville, Tennessee, 37232, United States

Location

Houston AIDS Research Team CRS (31473)

Houston, Texas, 77030, United States

Location

MeSH Terms

Interventions

Pravastatin; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Intervention Hierarchy (Ancestors)

Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Tenofovir; Organophosphonates; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Drug Combinations; Pharmaceutical Preparations

Study Officials

• David A. Wohl, M.D.

  University of North Carolina AIDS CRS

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2011
• First Posted: January 24, 2012
• Study Start: November 1, 2011
• Primary Completion: July 1, 2014
• Study Completion: December 1, 2014
• Last Updated: February 1, 2016

Record last verified: 2016-01

Locations

US (9)