Dipyridamole for Immune Activation in HIV

NCT02121756 | Completed Phase 1 Results DMC

• 2 other identifiers: DAIDS-ES ID 11987U01AI110410
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

HIV Infection

Keywords

Dipyridamole; HIV; Immune Markers; Immune Activation; Inflammation

Outcome Measures

Primary Outcomes (3)

• Monocyte and Macrophage Activation Assessed as Change in Plasma Levels of sCD14 From Baseline to Week 12

  Change in plasma levels of sCD14 from baseline to week 12

  Baseline to week 12

• Monocyte and Macrophage Activation Assessed as Change in Plasma Levels of sCD163 From Baseline to Week 12

  Change in Plasma levels of sCD163 from baseline to week 12

  baseline to week 12

• Systemic Inflammation Assessed as Change in IL-6 Plasma Levels From Baseline to Week 12

  Change in Plasma levels of IL-6 from baseline to week 12

  baseline to week 12

Secondary Outcomes (12)

• Immune System Activation as Measured by the Proportion of CD8+ T Cells Co-expressing CD69 and CD25 After 12 Weeks of Dipyridamole Treatment Compared to Placebo

  Baseline to week 12

• Safety and Tolerability of Dipyridamole Assessed as the Number of Participants With Grade 2 or Higher Adverse Events or Treatment Discontinuations

  First 12 weeks of dipyridamole treatment

• Immune System Activation Assessed as the Change in the Proportion of Cycling CD4+ T Cells as Measured by Ki-67 Expression at Baseline and After Treatment With Dipyridamole

  Baseline to week 12

• Immune System Activation as Measured by the Proportion of CD4+ T Cells Co-expressing HLA-DR and CD38 After 12 Weeks of Dipyridamole Treatment Compared to Placebo

  Baseline to week 12

• Immune System Activation as Measured by the Proportion of CD8+ T Cells Co-expressing HLA-DR and CD38 After 12 Weeks of Dipyridamole Treatment Compared to Placebo

  Baseline to week 12

Study Arms (2)

Dipyridamole

EXPERIMENTAL

ARM A: Dipyridamole 100 mg four (4) times daily for 24 weeks from Baseline to Week 24

Drug: Dipyridamole

Placebo then Dipyridamole

ACTIVE COMPARATOR

ARM B: Placebo for Dipyridamole four (4) times daily for 12 weeks from Baseline to Week 12 followed by Dipyridamole 100mg four (4) times daily for 12 weeks from Week 12 to Week 24

Drug: Placebo, then Dipyridamole

Interventions

Dipyridamole DRUG

Dipyridamole 100 mg four (4) times daily for 24 weeks from Baseline to Week 24

Also known as: Permole®, Persantine®

Dipyridamole

Placebo, then Dipyridamole DRUG

Placebo for Dipyridamole four (4) times daily for 12 weeks from Baseline to Week 12 followed by Dipyridamole 100mg four (4) times daily for 12 weeks from Week 12 to Week 24

Also known as: Permole®, Persantine®

Placebo then Dipyridamole

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, 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

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 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.

Sponsors & Collaborators

• Sharon Riddler: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

Pitt Treatment Evaluation Unit / University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Conditions

HIV Infections; Inflammation

Interventions

Dipyridamole

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Sharon Riddler, MD
• Organization: University of Pittsburgh Department of Medicine

riddler@pitt.edu

412-383-1675

Study Officials

• Sharon A. Riddler, MD, MPH

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: April 21, 2014
• First Posted: April 23, 2014
• Study Start: July 1, 2014
• Primary Completion: October 1, 2017
• Study Completion: November 1, 2017
• Last Updated: April 11, 2019
• Results First Posted: April 11, 2019

Record last verified: 2019-03

Locations

US (1)