Clinical trial NCT01781611: Dipyridamole Assessment for Flare Reduction in Systemic Lupus Erythematosus (SLE)
Official title: Dipyridamole Assessment for Flare Reduction in SLE
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Systemic Lupus Erythematosus
Keywords: lupus
dipyridamole
Lead sponsor: Oklahoma Medical Research Foundation
Sponsor class: OTHER
First posted: 2013-02-01
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Pilot study
Primary purpose: TREATMENT

Brief summary: Dipyridamole, a medication extensively used in combination with aspirin for stroke prevention, is a promising new treatment for lupus. Dipyridamole has been shown to inhibit certain lymphocyte populations that are over-reactive in lupus and to delay the emergence of lupus-related pathology in mice with lupus. The investigators are interested in investigating the efficacy of dipyridamole in preventing flares in patients with lupus and its impact on biomarkers of disease activity.

Detailed description: T cells in systemic lupus erythematosus (SLE) express an abnormal phenotype characterized by increased effector functions and deficient regulatory responses. Dipyridamole, a phosphodiesterase inhibitor extensively used in combination with low dose aspirin in secondary stroke prevention, has been proposed as a specific T cell directed treatment for SLE. Dipyridamole inhibits the calcium/calcineurin/NF-AT pathway in SLE T cells in vitro and abrogates expression of cytokines and costimulatory molecules, eventually also affecting B cell responses. Dipyridamole delays the emergence of lupus related pathology in lupus prone mice, but has not yet been studied in humans with SLE. The investigators aim to investigate the efficacy of dipyridamole in the prevention of flares in SLE patients after withdrawal of background immunosuppressive medications. The investigators will additionally evaluate the safety and tolerability of dipyridamole and its impact on quality of life measures in this population. Furthermore, the effect of dipyridamole on T and B cell biomarkers will be examined.

Eligibility criteria: Inclusion Criteria:

* Patients with SLE meeting the 1997 ACR Classification Criteria
* Evidence of positive ANA or anti-dsDNA within one year of screening
* SLEDAI ≥4 or ≥1 BILAG A or B at screening, despite standard of care

Exclusion Criteria:

* Leukopenia (WBC \<2.000/mm3) or lymphopenia (lymphocytes \< 300/mm3)
* AST or ALT \>3 times above normal cut off values
* Acute lupus nephritis defined as class II, IV or V nephritis diagnosed within 6 months or prot/creat \> 1.5 gm/gm due to active lupus or in process of receiving induction therapy for nephritis
* Active CNS lupus affecting mental status
* Pregnancy or breast feeding
* Current requirement for anticoagulation
* Contraindication to aspirin or dipyridamole, including history of recent or severe GI bleeding, hemoglobin \<9 mg/dL, platelet count of \<30,000 /mm3 or unstable platelet count
* Any other medical condition, whether or not related to lupus which, in the opinion of the investigator would render the patient inappropriate or too unstable to complete the study protocol
* Inability or unwillingness to understand and/or sign informed consent

Primary outcomes:
measure: British Isles Lupus Assessment Group Index-based Combined Lupus Assessment (BICLA)
timeFrame: 24 weeks
Secondary outcomes:
measure: Systemic Lupus Erythematosus Responder Index (SRI) 4
timeFrame: 24 weeks
measure: SRI Component Analyses: 4 Point Drop in SLEDAI
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Oklahoma City
country: United States
facility: Oklahoma Medical Research Foundation
state: Oklahoma
Study officials:
affiliation: Oklahoma Medical Research Foundation
name: Katherine Thanou, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kyttaris VC, Zhang Z, Kampagianni O, Tsokos GC. Calcium signaling in systemic lupus erythematosus T cells: a treatment target. Arthritis Rheum. 2011 Jul;63(7):2058-66. doi: 10.1002/art.30353.
citation: Hannon CW, McCourt C, Lima HC, Chen S, Bennett C. Interventions for cutaneous disease in systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2.