Dipyridamole Assessment for Flare Reduction in Systemic Lupus Erythematosus (SLE) (DARE)

Oklahoma Medical Research Foundation

Status

Terminated

Conditions

Systemic Lupus Erythematosus

Treatments

Drug: 81mg aspirin

Drug: extended release dipyridamole 200mg/aspirin 25mg

Study type

Interventional

Funder types

Other

Identifiers

NCT01781611

IRB# 12-10

Details and patient eligibility

About

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.

Full 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.

Enrollment

18 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

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