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Dipyridamole for Immune Activation in HIV

Information source: University of Pittsburgh
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: HIV Infection

Intervention: Dipyridamole (Drug); Placebo, then Dipyridamole (Drug)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: Sharon Riddler

Official(s) and/or principal investigator(s):
Sharon A. Riddler, MD, MPH, Principal Investigator, Affiliation: University of Pittsburgh

Overall contact:
Jennifer M. van Panhuis, BA, BSN, Phone: 412-624-5732, Email: jms367@pitt.edu


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.

Clinical Details

Official title: A Phase I/II Pilot Study of Dipyridamole as a Modulator of Immune Activation and Systemic Inflammation in HIV-1-Infected Subjects on Antiretroviral Therapy- DAIDS-ES ID 11987

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Change in plasma levels of immune activation inflammatory markers

Secondary outcome:

Change in plasma levels of immune activation inflammatory markers

Adverse events, discontinuations of study drug

Correlation of plasma Dipyridamole level to markers of immune activation and inflammation

Detailed description: Background:

- Since HIV-infected individuals started taking anti-HIV medications, illnesses from AIDS

have decreased, but other serious diseases have increased. Researchers think this may be caused by an increase in activity of the immune system that fights infection, leading to inflammation. Inflammation is a normal body reaction to any infection. However, if inflammation lasts a long time, like in HIV infection, it may lead to complications such as heart disease, cancer, liver disease, lung disease, and problems with thinking. Many HIV researchers are studying the harmful effects of this prolonged immune system activity and inflammation and possible ways to prevent these complications.

- A drug called dipyridamole is approved by the Food and Drug Administration (FDA) under

the trade name Persantine® for use with other drugs to reduce the risk of blood clots after heart valve replacement. Laboratory studies have shown that dipyridamole also lowers the level of immune system activity and inflammation measured in the blood. Objectives:

- To see how dipyridamole affects blood and lung tests to measure immune system activity

and inflammation and to look at the safety and tolerability of dipyridamole in people infected with HIV. This use of dipyridamole is investigational, or not approved by the FDA; however, the dose to be used in this study, 100mg four times a day, is the dose approved by the FDA. Eligibility:

- Individuals 18 years of age and older who have HIV infection and are taking medications

to treat it, and have a low viral load (HIV-1 RNA <50 copies/mL) for a minimum of 12 months. Design:

- Participants will be screened with a physical exam, blood test, and medical history.

Women of reproductive age will also receive a pregnancy test.

- Participants will take either Dipyridamole or a placebo for 12 weeks. Then they will

take Dipyridamole for 12 weeks.

- During the study, participants will have frequent blood and urine tests. Dipyridamole

drug levels, and liver and kidney function tests will be performed. HIV viral load (the amount of virus in the blood) will also be studied.

- Participants will have a final follow-up visit after an additional 4 weeks.

- Four brachial artery ultrasound images will be taken.

- Four pre- and post-bronchodilator spirometry tests will be performed by participants

enrolled under Version 2. 0: after each pre-test spirometry, participants will be asked to inhale 4 puffs of albuterol, and then to repeat the spirometry for post-testing.

- Participants will receive rectal swabs at screening, and four flexible sigmoidoscopies

with rectal biopsies of the sigmoid colon throughout the study. These studies of the lower colon and samples of the rectum will be used to explore the effects of Dipyridamole. Participants can, however, opt out of all rectal procedures.


Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.


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


- 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.

Locations and Contacts

Jennifer M. van Panhuis, BA, BSN, Phone: 412-624-5732, Email: jms367@pitt.edu

Pitt Treatment Evaluation Unit / University of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States; Recruiting
Renee Weinman, BS, CCRP, Phone: 412-647-0322, Email: weinmandr@upmc.edu
Sharon A. Riddler, MD, MPH, Principal Investigator
Bernard JC Macatangay, MD, Sub-Investigator
Kaleab Z. Abebe, PhD, Sub-Investigator
Aryan N. Aiyer, MD, Sub-Investigator
Cranston D. Cranston, MD, FRCP, Sub-Investigator
Ken S. Ho, MD, MPH, Sub-Investigator
Edwin K. Jackson, PhD, Sub-Investigator
Ian M. McGowan, MD, PhD, Sub-Investigator
Deborah K. McMahon, MD, Sub-Investigator
John W, Mellors, MD, Sub-Investigator
Ramakrishna Prasad, MD, MPH, Sub-Investigator
Charles R. Rinaldo, PhD, Sub-Investigator
Theresa L. Whiteside, PhD, Sub-Investigator
Randall E. Brand, MD, Sub-Investigator
Richard H. Duerr, MD, Sub-Investigator
Stacey M. Edick, PA-C, Sub-Investigator
Matthew R. Gingo, MD, MS, Sub-Investigator
Janet R. Harrison, MD, Sub-Investigator
Alison Morris, MS, MS, Sub-Investigator
Additional Information

Starting date: July 2014
Last updated: July 21, 2015

Page last updated: August 23, 2015

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