Dipyridamole for Immune Activation in HIV

• Status: Completed
• Trial end date: 2017-11-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to determine if Dipyridamole (DP) will decrease inflammation in HIV-1-infected individuals who are already on antiretroviral treatment and have a low viral load.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sharon Riddler
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Dipyridamole

Criteria

Inclusion Criteria:

• HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load.

• On ART for at least 12 months prior to study entry with a regimen that includes three or more antiretroviral medications. More information on this criterion is available in the protocol.

• Plasma HIV-1 RNA <50 copies/mL by any standard clinical assay at screening and for a minimum of 12 months prior to entry, confirmed by at least 2 measurements prior to study entry, one of which must be at least 48 weeks prior to study entry and one of which must be 61 days and 48 weeks prior to study entry. All plasma HIV-1 RNA measurements in the 12 months prior to study entry must be <50 copies/mL (with the exception that a single detectable measurement of ≤ 200 copies/mL is permitted if the RNA levels immediately before and after are <50 copies/mL).

• Stable ART regimen for at least 8 weeks prior to study entry and no plans to change ART regimen for at least 6 months following study entry.

• Ability and willingness to provide informed consent.

• In the opinion of the investigator, no medical, mental health or other condition that precludes participation.

• Laboratory values obtained within 60 days prior to entry.

• Hemoglobin ≥10.0 g/dL

• Platelet count ≥100,000/mm3

• INR ≤ 1.5 (for rectal tissue subset only)

• PTT <2x ULN (for rectal tissue subset only)

• AST and ALT < 2.5 x upper limit of normal (ULN)

• Total bilirubin < 2.5 x ULN (except if hyperbilirubinemia is secondary to atazanavir).

• Creatinine ≤ 1.5 x ULN

• Hepatitis B surface antigen negative

• Hepatitis C antibody negative (note: subject with HCV Ab positive is eligible if Hepatitis C RNA PCR (viral load) is undetectable)

• For females of reproductive potential, negative serum or urine pregnancy test at screening and within 72 hours prior to study entry. Females of reproductive potential include women who have not been post-menopausal for at least 24 consecutive months, (i.e., who have had menses within the preceding 24 months, or women who have not undergone surgical sterilization, specifically hysterectomy and/or bilateral oophorectomy).

• Females of reproductive potential who are participating in sexual activity that could lead to pregnancy must agree to use one method of acceptable contraception while receiving protocol-specified treatment and for 4 weeks after stopping the treatment. These methods include condoms (male or female) with or without a spermicidal agent; diaphragm or cervical cap with spermicide; intrauterine device (IUD); and hormone-based contraceptive.

• Females not of reproductive potential (girls who have not reached menarche, women who have been post-menopausal for at least 24 consecutive months, or women who have undergone surgical sterilization, e.g., hysterectomy, bilateral oophorectomy, or bilateral tubal ligation or salpingectomy) are eligible without requiring the use of a contraceptive. Self- report is acceptable documentation of sterilization, other contraceptive methods, and menopause.

• Rectal Tissue Subset only: Willing to abstain from receptive anal intercourse and practices involving insertion of anything in the rectum (drug, enema, penis, or sex toy) for 72 hours prior to rectal biopsy and for 7 days post-biopsy to minimize risk of bleeding complications.

Exclusion Criteria:

• Pregnancy or breast-feeding.

• Known allergy/sensitivity or any hypersensitivity to components of study drug(s) or their formulation.

• Known 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.

• 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.

• History of asthma requiring medical treatment within 2 years prior to study entry with the exception of the use of albuterol inhaler for mild intermittent asthma.

• Serious illness requiring systemic treatment and/or hospitalization within 14 days prior to entry.

• Use of any of the following medications for more than 3 consecutive days within the 60 days prior to study entry:

• Immunosuppressives (e.g., azathioprine, corticosteroids [physiologic replacement doses are allowed], cyclosporine, mycophenolate, NSAIDs (nonsteroidal anti-inflammatory drugs), sirolimus, sulfasalazine, tacrolimus)

• Immune modulators (e.g., cytokines [e.g., IL-2], granulocyte colony stimulating factor, growth hormone, tumor necrosis factor antagonists, thalidomide)

• Antineoplastic agents

• Anticoagulants (e.g., warfarin and heparin)

• Anti-platelet drugs (e.g., clopidogrel and aspirin)

• Vaccinations within 1 week prior to the pre-entry or study entry visits. Routine standard of care vaccinations including hepatitis A and/or B, influenza, pneumococcal, and tetanus are permitted if administered at least 7 days before pre-entry and entry evaluations.

• Participation on any HIV immunotherapy or therapeutic vaccination trials within 6 months prior to study entry.

• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.

• Use of investigational therapies within 30 days prior to study entry.

• Rectal Tissue Subset only:

• Abnormalities of the colorectal mucosa or significant colorectal symptom(s), which in the opinion of the study investigator represent a contraindication to biopsy (including but not limited to presence of any unresolved injury, infectious or inflammatory condition of the local mucosa, and presence of symptomatic external hemorrhoids.

• NOTE: Abnormalities of the colorectal mucosa will be assessed at the time of the enrollment flexible sigmoidoscopy. If no significant colorectal abnormalities or symptoms are present then the participant will undergo the enrollment procedures. If abnormalities are present then no biopsies will be performed and the participant will not be enrolled into the rectal tissue subset but will continue participation in the main study.

• Active untreated gonorrhea, or chlamydia infection within 30 days prior to study entry (subjects diagnosed with rectal gonorrhea or chlamydia infection at screening may be treated during the screening period provided the treatment is at least 30 days prior to entry).

• Exclusions for spirometry testing (for participants enrolled under Version 2.0) Participants will not undergo pre- and post-bronchodilator spirometry if they have any of the following: - Abdominal or cataract surgery within 3 months.

• Myocardial infarction or stroke within the past 3 months.

• Acute onset of shortness of breath, cough, fever or heart condition such as tachycardia, angina or arrhythmias with 4 weeks prior to enrollment.

• Increasing respiratory symptoms or febrile (temperature >100.4°F [38°C]) within 4 weeks of study entry.

• Uncontrolled hypertension defined as systolic > 160 mm Hg or diastolic > 100 mm Hg from an average of two or more readings. Participant with controlled hypertension may undergo spirometry.

• Prior history of adverse reaction to albuterol.