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

This study is not yet open for participant recruitment.
Verified January 2013 by Oklahoma Medical Research Foundation
Sponsor:
Collaborator:
Oklahoma Rheumatic Disease Research Cores Center
Information provided by (Responsible Party):
Aikaterini Thanou, Oklahoma Medical Research Foundation
ClinicalTrials.gov Identifier:
NCT01781611
First received: January 2, 2013
Last updated: January 30, 2013
Last verified: January 2013
History of Changes
  Purpose

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.


Condition Intervention
Systemic Lupus Erythematosus
 Drug: extended release dipyridamole 200mg/aspirin 25mg
Drug: aspirin 81mg

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Dipyridamole Assessment for Flare Reduction in SLE

Resource links provided by NLM:

MedlinePlus related topics: Lupus
U.S. FDA Resources

Further study details as provided by Oklahoma Medical Research Foundation:

Primary Outcome Measures:
  • British Isles Lupus Assessment Group Responder Index (BICLA) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to first flare [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Systemic Responder Index (SRI) 4/5 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Health related quality of life [Lupus Quality of Life (Lupus QoL), Short Form 36v2] [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Fatigue (FACIT-fatigue score) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Sleep quality [Pittsburgh Sleep Quality Index (PSQI)] [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Depression [Center for Epidemiologic Studies Depression (CES-D) Scale] [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • SRI component analyses [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Cutaneous Lupus Disease Area and Severity Index (CLASI) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • serum immunoglobulins [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • serum cytokines [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • T and B cell immunophenotyping [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • T cell biomarkers after in vitro T cell stimulation [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • T and B cell gene expression profiling [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Heart rate variability [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: February 2013
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: extended release dipyridamole/aspirin
extended release dipyridamole 200mg/aspirin 25mg twice daily for 24 weeks
 Drug: extended release dipyridamole 200mg/aspirin 25mg
one tablet twice daily for 24 weeks
Other Name: Aggrenox
Active Comparator: aspirin
aspirin 81mg twice daily for 24 weeks
 Drug: aspirin 81mg
once tablet twice daily for 24 weeks

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

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 lymhopenia (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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01781611

Contacts
Contact: Aikaterini Thanou, MD 405-271-7805 aikaterini-thanou@omrf.org

Locations
United States, Oklahoma
Oklahoma Medical Research Foundation Not yet recruiting
Oklahoma City, Oklahoma, United States, 73104
Sponsors and Collaborators
Oklahoma Medical Research Foundation
Oklahoma Rheumatic Disease Research Cores Center
Investigators
Principal Investigator: Aikaterini Thanou, MD Oklahoma Medical Research Foundation
  More Information

Publications:

Responsible Party: Aikaterini Thanou, Assistant Member, Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation
ClinicalTrials.gov Identifier: NCT01781611     History of Changes
Other Study ID Numbers: IRB# 12-10
Study First Received: January 2, 2013
Last Updated: January 30, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Oklahoma Medical Research Foundation:
lupus
dipyridamole

Additional relevant MeSH terms:
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Aspirin
Dipyridamole
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
 Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Central Nervous System Agents
Phosphodiesterase Inhibitors
Vasodilator Agents

ClinicalTrials.gov processed this record on May 21, 2013