Modulation of Immune Activation by Aspirin

NCT02155985 | Completed Phase 2 Results DMC

• 2 other identifiers: ACTG A5331UM1AI068636
• Study Type: interventional
• Target: 121
• Locations: 1 country
• Sites: 15

Brief Summary

Since people started taking HIV medications, illness from AIDS has decreased, but other serious diseases like heart disease, cancer, and kidney, and liver disease have increased. HIV causes inflammation (irritation) inside the body that cannot be felt but can be measured by blood. Inflammation can lead to diseases that have become some of the leading causes of death in people with HIV. HIV therapy can partially lower levels of inflammation measured in blood, however, levels of inflammation in people who have HIV may remain high compared with people not infected with HIV. Aspirin is a drug that is commonly used for pain relief but is also approved by the Food and Drug Administration (FDA) for preventing heart attacks and stroke in those who are at increased risk for heart attack and stroke. Aspirin also is used (but is not approved by the FDA) to decrease the risk of some cancers in people who are at increased risk. Aspirin is thought to decrease risk of heart attack and stroke because it blocks the activation of platelets and prevents blood clots from clogging narrowed blood vessels, a disease called atherosclerosis. It is unknown how aspirin might decrease the chance of developing cancer in some people at higher risk, but aspirin has been shown to modulate (or change) the immune system. In HIV-infected people who have been taking antiretroviral therapy and have an undetectable HIV viral load it was recently shown that low-dose aspirin 81 mg (baby aspirin), given for one week, lowers platelet activation and reduces blood markers of inflammation which may improve the function of the immune system. The purpose of this study was to evaluate whether aspirin improves inflammation and immune activation when compared to a placebo (inactive medication like a dummy pill) and to determine if 12 weeks of aspirin 300 mg and aspirin 100 mg is safe for HIV-infected persons on antiretroviral therapy. Additionally, it studied whether a higher dose and longer duration of aspirin provides further anti-inflammatory and immune-modulating benefit. This was done using blood and urine tests that measure inflammation and also with a test that uses ultrasound to measure the flow of blood in your arm, called flow-mediated vasodilation (FMD) of the brachial artery (BART). This is a painless test that bounces sound waves off of a blood vessel in your arm.

Conditions

HIV-1 Infection

Outcome Measures

Primary Outcomes (1)

• Change in sCD14 From Baseline to Week 11/12

  Baseline is defined as the average of the Pre-Entry and Entry values. Week 11/12 is defined as the average of the Week 11 and Week 12 values. All values were log10 transformed prior to calculating change and conducting analyses. Values obtained within 6 days after the influenza vaccination were excluded. Absolute change was calculated as the value at week 11/12 minus the value at baseline. Mean changes were exponentiated to be back on the untransformed scale and corresponds to a mean fold change. Differences between arms are expressed as the percent difference between mean fold changes.

  Pre-entry and entry to weeks 11 and 12

Secondary Outcomes (19)

• Safety

  After study entry to Week 16

• Tolerability

  Treatment dispensation to Week 12

• Change in sCD163 From Baseline to Week 11/12

  Pre-entry and entry to weeks 11 and 12

• Change in Expression of CD14dimCD16+ From Entry to Week 12

  Entry to Week 12

• Change in Expression of CD69+ on CD14dimCD16+ From Entry to Week 12

  Entry to Week 12

Study Arms (3)

Aspirin 300 mg + aspirin 100 mg placebo

ACTIVE COMPARATOR

At week 0, participants were prescribed aspirin 300 mg (one tablet) and placebo for aspirin 100 mg (one tablet) once daily. At week 12, participants were to stop both study product tablets to allow for a 4-week washout period.

Drug: Aspirin; Drug: Placebo

Aspirin 100 mg + aspirin 300 mg placebo

ACTIVE COMPARATOR

At week 0, participants were prescribed a placebo for aspirin 300 mg (one tablet) and aspirin 100 mg (one tablet) once daily. At week 12, participants were to stop both study product tablets to allow for a 4-week washout period.

Drug: Aspirin; Drug: Placebo

Aspirin 300 mg + aspirin 100 mg placebos

PLACEBO COMPARATOR

At week 0, participants were prescribed a placebo for aspirin 300 mg (one tablet) and placebo for aspirin 100 mg (one tablet) once daily. At week 12, participants were to stop both study products tablets to allow for a 4-week washout period.

Drug: Placebo

Interventions

Aspirin DRUG

Aspirin is a nonsteroidal antiinflammatory drug (NSAID) effective in treating fever, pain, and inflammation in the body.

Aspirin 100 mg + aspirin 300 mg placebo; Aspirin 300 mg + aspirin 100 mg placebo

Placebo DRUG

Placebo for aspirin

Aspirin 100 mg + aspirin 300 mg placebo; Aspirin 300 mg + aspirin 100 mg placebo; Aspirin 300 mg + aspirin 100 mg placebos

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.
• Currently on continuous ART for ≥48 weeks prior to study entry. NOTE: This is defined as continuous active therapy with no treatment interruption longer than 7 consecutive days and a total duration off-treatment of no more than 14 days during the 48 weeks prior to entry.
• No change in ART regimen within the 12 weeks prior to study entry (except as noted below).
• NOTE: Modifications of ART dosing during within the 12 weeks prior to entry are permitted. In addition, the change in formulation (eg, from standard formulation to fixed dose combination or single tablet regimen) or dosing (eg, from once a day to twice a day) is allowed within 12 weeks prior to entry. Within-class single drug substitution (eg, switch from nevirapine to efavirenz or from atazanavir to darunavir), are not allowed within 12 weeks prior to entry. No other changes in ART in the 12 weeks prior to entry are permitted.
• Screening HIV-1 RNA must be \<50 copies/mL and performed by any FDA-approved assay at any US laboratory that has a CLIA certification or its equivalent within 45 days prior to study entry.
• Maintain ART-mediated viral suppression for at least 48 weeks prior to study entry defined as:
• A. At least one HIV-1 RNA test result obtained at any time point greater than 48 weeks prior to study entry must be BLQ and must be performed by any FDA-approved assay at a CLIA-certified laboratory or its equivalent.
• AND
• B. All HIV-1 RNA tests reported during the 48 weeks prior to study entry must be BLQ and must be performed by any FDA-approved assay at a CLIA-certified laboratory or its equivalent.
• NOTE: A single RNA "blip" of ≤500 copies/mL is permissible if RNA levels most recent before and after (may include the screening HIV-1 RNA test) are below the level of quantification (BLQ) for the assay. If the RNA level after the blip is the screening HIV-1 RNA test, the result must be \<50 copies/mL.
• The following laboratory values obtained within 45 days prior to study entry by any US laboratory that has a CLIA certification or its equivalent.
• Absolute neutrophil count (ANC) ≥750/mm\^3
• Hemoglobin ≥9.0 g/dL for female subjects and ≥10.0 g/dL for male subjects
• Platelet count \>100,000/mm\^3
• Prothrombin time (PT) \<1.2 x upper limit normal (ULN)

You may not qualify if:

• \- Current malignancy (except non-melanoma cancer of the skin not requiring systemic chemotherapy or radiation therapy).
• Prior history of malignancy if the subject is not disease free for 24 or more weeks prior to study entry.
• Current use or indication for use of non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin that cannot be interrupted for clinical reasons. Examples of clinical reasons include, but are not limited to, 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).
• Current diagnosis of diabetes with HbA1c ≥8% within 24 weeks prior to screening.
• Changes in lipid-lowering or antihypertensive medication within 90 days prior to study entry or expected need to modify these medications during the study.
• NOTE: Lipid-lowering medication includes: statins, fibrates, niacin (dose ≥250 mg daily), and fish-oil/omega 3 fatty acids (dose \>1000 mg of marine oils daily).
• Known cirrhosis
• Known chronic active hepatitis B NOTE: Active hepatitis B is defined as hepatitis B surface antigen positive and hepatitis B DNA positive within 24 weeks prior to study entry; subjects with hepatitis B virus (HBV) DNA BLQ for greater than 24 weeks prior to study entry are eligible.
• Known chronic active hepatitis C NOTE: Active hepatitis C is defined as a detectable plasma HCV RNA level within 24 weeks prior to study entry; subjects with HCV RNA BLQ for greater than 24 weeks prior to study entry are eligible.
• Known inflammatory conditions, such as, but not limited to, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), sarcoidosis, inflammatory bowel disease (IBD), chronic pancreatitis, autoimmune hepatitis, Adult Stills disease, Rheumatic heart disease, bursitis.
• Breastfeeding or pregnant
• Previous intolerance or allergy to aspirin or any aspirin products.
• Frequent use of aspirin or aspirin products (NSAIDs), defined as an average of 2 or more times per week in the last 12 weeks prior to study entry.
• Immunosuppressant use, such as, but not limited to, systemic or potentially systemic glucocorticoids (including injected, ie, intra-articular, nasal or inhaled steroids), azathioprine, tacrolimus, mycophenolate, sirolimus, rapamycin, methotrexate, or cyclosporine within 45 days prior to study entry.
• Use of any systemic antineoplastic or immunomodulatory treatment, investigational vaccines, interleukins, interferons, growth factors, or intravenous immunoglobulin (IVIG) within 45 days prior to study entry.

Sponsors & Collaborators

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

Study Sites (15)

601 University of California, Los Angeles CARE Center CRS

Los Angeles, California, 90035, United States

Location

701 University of California, San Diego AntiViral Research Center CRS

San Diego, California, 92103, United States

Location

Ucsf Aids Crs (801)

San Francisco, California, 94110, United States

Location

Harbor-UCLA Med. Ctr. CRS (603)

Torrance, California, 90502, United States

Location

University of Colorado Hospital CRS (6101)

Aurora, Colorado, 80045, United States

Location

2701 Northwestern University CRS

Chicago, Illinois, 60611, United States

Location

Rush Univ. Med. Ctr. ACTG CRS (2702)

Chicago, Illinois, 60612, United States

Location

Massachusetts General Hospital ACTG CRS (101)

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hosp. ACTG CRS (107)

Boston, Massachusetts, 02115, United States

Location

3201 Chapel Hill CRS

Chapel Hill, North Carolina, 27516, United States

Location

Greensboro CRS (3203)

Greensboro, North Carolina, 27401, United States

Location

Univ. of Cincinnati CRS (2401)

Cincinnati, Ohio, 45267, United States

Location

Case CRS (2501)

Cleveland, Ohio, 44106, United States

Location

3652 Vanderbilt Therapeutics (VT) CRS

Nashville, Tennessee, 37204, United States

Location

Houston AIDS Research Team CRS (31473)

Houston, Texas, 77030, United States

Location

Related Links

• Version 2.0 of the DAIDS EAE Manual
• DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004 (Clarification, August 2009),

MeSH Terms

Interventions

Aspirin

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: ACTG Clinicaltrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.

ACTGCT.Gov@s-3.com

(301) 628-3313

Study Officials

• Judith A Aberg, MD

  Icahn School of Medicine at Mount Sinai

  STUDY CHAIR

• Meagan O'Brien, MD

  Icahn School of Medicine at Mount Sinai

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2014
• First Posted: June 4, 2014
• Study Start: August 1, 2014
• Primary Completion: June 1, 2015
• Study Completion: July 1, 2015
• Last Updated: June 12, 2017
• Results First Posted: July 7, 2016

Record last verified: 2017-05

Locations

US (15)