Dataset Information

A Randomized, Placebo-Controlled, Pilot Clinical Trial of Dipyridamole to Decrease Human Immunodeficiency Virus-Associated Chronic Inflammation.

ABSTRACT:

Background

Adenosine is a potent immunoregulatory nucleoside produced during inflammatory states to limit tissue damage. We hypothesized that dipyridamole, which inhibits cellular adenosine uptake, could raise the extracellular adenosine concentration and dampen chronic inflammation associated with human immunodeficiency virus (HIV) type 1.

Methods

Virally suppressed participants receiving antiretroviral therapy were randomized 1:1 for 12 weeks of dipyridamole (100 mg 4 times a day) versus placebo capsules. All participants took open-label dipyridamole during weeks 12-24. Study end points included changes in markers of systemic inflammation (soluble CD163 and CD14, and interleukin 6) and levels of T-cell immune activation (HLA-DR+CD38+).

Results

Of 40 participants who were randomized, 17 dipyridamole and 18 placebo recipients had baseline and week 12 data available for analyses. There were no significant changes in soluble markers, apart from a trend toward decreased levels of soluble CD163 levels (P = .09). There was a modest decrease in CD8+ T-cell activation (-17.53% change for dipyridamole vs +13.31% for placebo; P = .03), but the significance was lost in the pooled analyses (P = .058). Dipyridamole also reduced CD4+ T-cell activation (-11.11% change; P = .006) in the pooled analyses. In post hoc analysis, detectable plasma dipyridamole levels were associated with higher levels of inosine, an adenosine surrogate, and of cyclic adenosine monophosphate.

Conclusion

Dipyridamole increased extracellular adenosine levels and decreased T-cell activation significantly among persons with HIV-1 infection receiving virally suppressive therapy.

SUBMITTER: Macatangay BJC

PROVIDER: S-EPMC7184919 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A Randomized, Placebo-Controlled, Pilot Clinical Trial of Dipyridamole to Decrease Human Immunodeficiency Virus-Associated Chronic Inflammation.

Macatangay Bernard J C BJC Jackson Edwin K EK Abebe Kaleab Z KZ Comer Diane D Cyktor Joshua J Klamar-Blain Cynthia C Borowski Luann L Gillespie Delbert G DG Mellors John W JW Rinaldo Charles R CR Riddler Sharon A SA

The Journal of infectious diseases 20200401 10

<h4>Background</h4>Adenosine is a potent immunoregulatory nucleoside produced during inflammatory states to limit tissue damage. We hypothesized that dipyridamole, which inhibits cellular adenosine uptake, could raise the extracellular adenosine concentration and dampen chronic inflammation associated with human immunodeficiency virus (HIV) type 1.<h4>Methods</h4>Virally suppressed participants receiving antiretroviral therapy were randomized 1:1 for 12 weeks of dipyridamole (100 mg 4 times a da ...[more]

PMID: 31282542

Similar Datasets

Project description:BackgroundNew pharmacological targets are needed for restless legs syndrome. Preclinical data suggest that a hypoadenosinergic state plays an important pathogenetic role.ObjectiveThe objective of this study was to determine whether inhibitors of equilibrative nucleoside transporters, for example, dipyridamole, could provide effective symptomatic treatment.MethodsA 2-week double-blind, placebo-controlled crossover study assessed the efficacy of dipyridamole (possible up-titration to 300 mg) in untreated patients with idiopathic restless legs syndrome. Multiple suggested immobilization tests and polysomnography were performed after each treatment phase. Severity was assessed weekly using the International Restless Legs Rating Scale, Clinical Global Impression, and the Medical Outcomes Study Sleep scale. The primary end point was therapeutic response.ResultsTwenty-eight of 29 patients recruited were included. International Restless Legs Rating Scale scores improved from a mean ± standard deviation of 24.1 ± 3.1 at baseline to 11.1 ± 2.3 at the end of week 2, versus 23.7 ± 3.4 to 18.7 ± 3.2 under placebo (P < 0.001). Clinical Global Impression, Medical Outcomes Study Sleep, and Multiple Suggested Immobilization Test scores all improved (P < 0.001). The mean effective dose of dipyridamole was 217.8 ± 33.1 mg/d. Sleep variables improved. The mean periodic leg movement index at the end of treatment with dipyridamole was 8.2 ± 3.5 versus. 28.1 ± 6.7 under placebo. Side effects (dipyridamole vs placebo) included abdominal distension (18% vs. 7%), dizziness (10.7% vs 7.1%), diarrhea, and asthenia (each 7.1% vs 3.6%).ConclusionsDipyridamole has significant therapeutic effects on both sensory and motor symptoms of restless legs syndrome and on sleep. Our findings confirm the efficacy of dipyridamole in restless legs syndrome predicted from preclinical studies and support a key role of adenosine in restless legs syndrome. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Dataset Information

A Randomized, Placebo-Controlled, Pilot Clinical Trial of Dipyridamole to Decrease Human Immunodeficiency Virus-Associated Chronic Inflammation.

Background

Methods

Results

Conclusion

Publications

A Randomized, Placebo-Controlled, Pilot Clinical Trial of Dipyridamole to Decrease Human Immunodeficiency Virus-Associated Chronic Inflammation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets